Goat's milk allergy without cow's milk allergy: suppression of non-cross-reactive epitopes on caprine ß-casein.

BACKGROUND AND OBJECTIVE: Goat's milk (GM) allergy associated with tolerance to cow's milk (CM) has been reported in patients without history of CM allergy and in CM-allergic children successfully treated with oral immunotherapy. The IgE antibodies from GM-allergic/CM-tolerant patients recognize caprine ß-casein (ßcap) without cross-reacting with bovine ß-casein (ßbov) despite a sequence identity of 91%. In this study, we investigated the non-cross-reactive IgE-binding epitopes of ßcap. METHODS: Recombinant ßcap was genetically modified by substituting caprine domains with the bovine counterparts and by performing site-directed mutagenesis. We then evaluated the recognition of modified ßcap by IgE antibodies from 11 GM-allergic/CM-tolerant patients and 11 CM-allergic patients or by monoclonal antibodies (mAb) raised against caprine caseins. The allergenic potency of modified ßcap was finally assessed by degranulation tests of humanized rat basophil leukaemia (RBL)-SX38 cells. RESULTS: Non-cross-reactive epitopes of ßcap were found in domains 44-88 and 130-178. The substitutions A55T/T63P/L75P and P148H/S152P induced the greatest decrease in IgE reactivity of GM-allergic/CM-tolerant patients towards ßcap. The pivotal role of threonine 63 was particularly revealed as its substitution also impaired the recognition of ßcap by specific mAb, which could discriminate between ßcap and ßbov. The modified ßcap containing the five substitutions was then unable to trigger the degranulation of RBL-SX38 cells passively sensitized with IgE antibodies from GM-allergic/CM-tolerant patients. CONCLUSIONS: Although IgE-binding epitopes are spread all over ßcap, a non-cross-linking version of ßcap was generated with only five amino acid substitutions and could thus provide new insight for the design of hypoallergenic variants.

Drug-induced enterocolitis syndrome (DIES) in a 10-year-old girl.

We report the case of a child presenting with an adverse drug reaction highly suggestive of drug-induced enterocolitis syndrome (DIES) to amoxicillin (AMX). A 10-year-old girl developed repetitive vomiting and pallor without cutaneous or respiratory symptoms 2h after AMX intake. DIES is not a well-described entity, and very few data are available in the literature. In the absence of an existing definition, the diagnosis of DIES can only be suspected and is based on its homology with food protein-induced enterocolitis (FPIES). The major criterion is the recurrence of repetitive and often incoercible vomiting occurring within 1-4h of ingestion of the culprit food in the absence of IgE-mediated allergic classic skin and respiratory symptoms. Once the diagnosis of DIES to AMX is suspected, an open challenge with AMX should be undertaken with caution, under medical supervision in a day hospital unit because of the risk of severe recurrence. Once the diagnosis is confirmed, AMX should be contraindicated to avoid severe reactions.

Oral food challenge in children: an expert review.

Oral food challenges are indicated for the diagnosis of food allergy and the double-blind, placebo-controlled oral food challenge is considered the gold standard diagnostic method in children with suspected food allergy. This practice parameter for oral food challenges in children was prepared by a workgroup at the request of the French Society for Allergology and Clinical Immunology (SFAIC) and the French Paediatric Society for Allergology and Pulmonology (SP2A). We aimed to develop practical guidelines for oral food challenges in children for the diagnosis of suspected food allergy or the evaluation of food tolerance. We also considered the safety measures to be implemented during testing and management of the potentially serious allergic reactions that may arise during the test. The strength of the recommendations was established, using the GRADE evidence-based approach. We considered four issues: (1) the selection of children for oral food challenges (indications and contraindications); (2) the procedure used (material, where the test should be carried out, technique and management of reactions); (3) interpretation of the test and (4) consequences of the test.

[Diagnosing and food allergy in children]. / Bilan allergologique d'allergie alimentaire.

Values of allergic tests in childhood food allergies are discussed. Diagnosis procedures are then proposed depending of clinical pictures.

[Food hypersensibility: inhalation reactions are different from ingestion reactions]. / Allergie alimentaire : les réactions à l'inhalation sont différentes des réactions à l'ingestion.

Eight children, aged from 3 to 9 years, presented to inhaled peanut an immediate allergic reaction. All were sensitized to peanut but none had already ingested it overtly. A strict avoidance diet was prescribed concerning this food allergen. An oral provocation challenge was realized to determine the eliciting dose (ED) to ingestion. The ED was high enough to allow all the children a less restrictive diet. Inhaled allergic reaction to peanut does not always justify a strict avoidance diet.

[A diagnostic questionnaire for the hyperventilation syndrome in children]. / Elaboration d'un questionnaire diagnostique du syndrome d'hyperventilation chez l'enfant.

INTRODUCTION: Intensive efforts should be made to diagnose the hyperventilation syndrome (HVS) at an early stage as this will prevent stigmatisation and reinforcement of symptoms. It will also prevent children from undergoing unnecessary medical examinations and treatment. A diagnostic questionnaire should be useful for this purpose. METHODS: We administered a questionnaire with 16 respiratory symptoms and 23 non respiratory symptoms to 25 children with HVS alone, 20 with asthma and HVS, and two control groups: 20 children with asthma without HVS and 20 presenting with trauma. For each symptom a visual analogue scale (VAS) was completed. The symptoms for which the mean VAS values were significantly different between the children with HVS and the controls were subject to principal component analysis after varimax rotation with Kaiser normalisation. RESULTS: There was no significant difference in symptoms between HVS children with or without asthma. The five major respiratory symptoms were: throat-clearing, sniffing, difficulty in breathing in, sighing and yawning. The combined sensitivity of those symptoms was 99%, the combined specificity 24%. The five major non-respiratory symptoms were: anxiety, difficulty in going to sleep, general fatigue, abdominal pain, and joint pains. The combined sensitivity of those symptoms was 99%, the combined specificity 36%. CONCLUSIONS: We performed a simplified diagnostic questionnaire for HVS in healthy and asthmatic children and found 5 respiratory and 5 non-respiratory symptoms of significance.

[Food allergy in children]. / Allergie alimentaire de l'enfant.

Food allergy is an adverse reaction to food protein by an immunological mechanism (IgE or non IgE-mediated). Signs can involve all organs, but atopic dermatitis remains the main manifestation. In children, only few allergens are involved. In France, it is cow milk, hen eggs, kiwi, peanut, fish, nuts, shrimp. Diagnosis is based on clinical history, skin tests, specific IgE and, sometimes, food challenge. Treatment is based on specific eviction. Regime can be total or sometimes limited to large among of the specific food, or only raw food. Food allergy disappears sometimes. Tolerance or food desensitization is in progress.

[Mosquito bites allergy, which prevention?]. / Réactions allergiques aux piqûres de moustiques, quelle prévention?

Mosquito bites may induce allergic reactions in children. Usually underestimated, these reactions are often cutaneous and difficult to distinguish from non-specific histaminic phenomena. Recently, the identification of major allergens in mosquito saliva has allowed the achievement of recombinant allergens, which should facilitate the diagnosis and treatment of allergic reactions. Preventive cares must be performed in all children with large reactions, allergic or even non-allergic. Prevention consists in cutaneous protection, the use of repellents (with special attention to their toxicity), and antihistamines. A practical sheet for patient is provided.

[What type of avoidance for peanut allergic children?]. / Le régime d'éviction chez les allergique à l'arachide.

We analyzed, from the literature, the balance benefit/risk of a strict avoidance of peanut in children with peanut allergy. The benefits of a strict avoidance diet seem limited: reactions to the low doses and to the peanut oil refined are rare and most often slight. It is not proven that a strict avoidance facilitates the cure of allergy. On the other hand, strict avoidance could induce a worsening of allergy, with deterioration of quality of life, creation of food neophobia. In case of cure of allergy, it is difficult to normalize the diet after a strict avoidance. Outside of the rare sensitive patients to a very low dose of peanut, for which a strict avoidance is counseled, the report benefits risk is in favor of the prescription of adapted avoidance to the eliciting dose. For the majority of the peanut allergic children, it seems to us that the avoidance can and must be limited to the non hidden peanut.

[Hyperventilation syndrome in children]. / Le syndrome d'hyperventilation pulmonaire chez l'enfant, revue de la litterature.

Hyperventilation syndrome is frequent in adults. There are only very few and very ancient publications in children. Diagnosis is sometimes difficult, because the symptoms often mimic those of organic diseases. Hyperventilation syndrome and organic diseases, especially asthma, often coincide. Intensive efforts should be made to diagnose hyperventilation syndrome at an early stage because this will prevent stigmatization and fixation of symptoms and disease, and also prevent children from undergoing unnecessary medical examinations and therapies. The authors review the literature about hyperventilation syndrome in children.

[Written asthma action plans: a useful tool for self-management]. / Le plan d'action écrit : un outil pour l'autogestion de l'asthme.

Written action plans for asthma have been recommended for many years. However, despite the fact that their effectiveness has been demonstrated, they are not used enough. The plans that we propose are serviceable and the method that we suggest makes them easy to use in the treatment of asthmatic children. These plans are made for patients who do not use a peak-flow meter (plans based on symptoms) and those who control this tool (plans based on peak expiratory flow).

[Compliance with and acceptability of a new electronic peak flow meter, the PiKo-1]. / Observance et acceptabilité d'un nouveau débitmètre de pointe electronique, le PiKo-1.

BACKGROUND: Monitoring airflow obstruction is an essential component of asthma management. We examined home recording of PEFR using a new electronic peak flow meter in terms of compliance and acceptability in a group of children with asthma. METHODS: Twenty three children (3 with intermittent asthma and 20 with persistent asthma) (average age 10.9 +/- 3.8 [5-18] yrs) were asked to assess their PEFR every day during a period of 5.8 +/- 1.2 [4-8] weeks and record it in a diary card. Patients were not aware that their data was also being stored on the PiKo-1. At the end of the study, the written data were compared to the stored data. A multiple choice questionnaire was given to each subjectto check the acceptability of the PiKo-1. RESULTS: 2 patients were lost to follow up. The compliance (expressed as a percent of the number of recordings that should have been made) was more that 80% for 14/21(67%) patients and less than 45% for 3/21 (14%). Compliance decreased during the study (96% in the first week, 68% during the fifth). 12% of the values were falsified. The PiKo-1 was considered to be small, attractive and useful. Some children found the mouthpiece too small. CONCLUSION: The good results for compliance that we observed might have been due to the short duration of the study. PiKo-1 was well accepted by the subjects. It will be possible to monitor PEFR and forced expiratory volume in the first second of expiration at home using this new device.

[Persistent coughs in children and adolescents]. / Toux traînantes chez l'enfant et l'adolescent.

A persistent cough lasting more than 4-8weeks should lead to a diagnostic workup. A detailed history and a full clinical examination, with a chest X-ray, are essential for initial assessment. Most reported causes of chronic cough in children are post-nasal drip syndrome, cough variant asthma (a spirometry with test of bronchodilator responsiveness should be attempted in children old enough to perform the manoeuvres). GERD is often suspected but a causal relationship is difficult to establish. Protracted bacterial bronchitis, post-infectious cough (B. pertussis, Mycoplasma) and somatoform respiratory disorders (including hyperventilation syndrome) are also common. Signs which are pointers suggesting an underlying respiratory or systemic disease require further investigation: inhaled foreign bodies, cystic fibrosis and chronic lung diseases with bronchiectasis, airway abnormalities, interstitial lung diseases need to be considered. Recent reports of refractory coughs have identified features of a sensory neuropathy disorder, and might explain persistent cough triggers.

[A notice for use for patients who benifit from an adrenaline pen. "Having an emergency kit is a good thing but knowing how to use it is better"]. / Une notice à l'usage du patient bénéficiant d'un stylo d'adrénaline. "Avoir une trousse d'urgence c'est bien, savoir l'utiliser en cas de besoin, c'est mieux".

We realized that it is essential that the patient who has an auto injector also has the direction sheet in its emergency bag. Patients, families but also young medical doctors' remarks and reflexions led us to create an explanatory didactic, precise, illustrated and practical direction sheet. The goals are to gather succinct information about the patient (personal contact information, medical history); remind emergency numbers (15 or 112) and the emergency treatment (antihistamine, broncholitor if necessary, epinephrine shots). It also indicates step by step how to use the auto injector (Anapen) and emphasizes the need for a medical supervision if the shot has been used. We present this direction sheet and the way to use it.

Sesame seed allergy in children.

BACKGROUND: Sesame seed allergy is becoming more common in childhood. The aim of this study is to define the clinical signs and the results of allergological work-up of this food allergy as well as the demographical data in children. Sesame seed allergy outcome is unknown. MATERIALS AND METHODS: 14 children were recruited from 3 allergy centers in France. The diagnosis of food allergy was based on a convincing clinical history and positive skin prick tests and/or an elevated sesame specific IgE. Food challenge test was done when results of history and allergological work-up were conflicting. A reintroduction test was done when a child seemed to outgrow his (or her) food allergy. RESULTS: The median age at the beginning of sesame seed allergy was 5 years (range from 5 months to 16 years old). All patients reacted immediately after sesame seed consumption and presented as a first manifestation: edema (9 cases, 48%), urticaria (5, 27%), and one of each of the following symptoms (vomiting, rhinitis, conjunctivitis, asthma and anaphylactic shock). One patient had recurrent anaphylactic shocks and another an anaphylactic shock after subsequent sesame seed exposure; these 2 patients were asthmatic. The median of the wheal size was 5 mm (range 3 to 15 mm). The commercial sesame seed extract was less sensitive than the native seed. The median of sesame seed IgE was 5.58 kUA/L (range 0.35 to 100 kUA/L). The follow up lasted from a few months to 6 years. Three patients outgrew their food allergy. All of these patients showed a previous drop of sesame seed IgE and skin prick-tests became negative. CONCLUSION: Sesame seed allergy is not very different than other food allergy. We reported the spontaneous outgrowing of sesame seed allergy without being able to define the predictive criteria for a good outcome.

[Vaccination in children with egg allergy]. / Vaccination chez l'enfant allergique à l'oeuf.

Vaccination of children who are allergic or assumed allergic to eggs still creates concern and complication for both the doctor and the patient. These concerns are based on a 1985 circular which has always been liberally interpreted and not well understood. Further analysis of the circular and a review of recent literature show, that most of the time, no special precautions need to be taken before vaccination of children with egg allergy.

[Comparative study of nebulized sambutol against placebo in the acute phase of bronchiolitis in 33 infants aged 1 to 6 months]. / Etude comparative des nébulisations de salbutamol contre placebo à la phase aiguë d'une bronchiolite chez 33 nourrissons de 1 à 6 mois.

BACKGROUND: The therapeutic role of bronchodilators in bronchiolitis remains controversial. The aim of this study is to evaluate the safety and the clinical response to nebulized salbutamol in infants with mild acute bronchiolitis. PATIENTS AND METHODS: Thirty-three infants, aged 1 month to 5 months and 22 days (mean: 92.4 days) were included in the study. Patients received either nebulized salbutamol (0.15 mg/kg per dose: 16 infants) or a placebo (normal saline aerosol: 17 infants), delivered by an oxygen propellent, three times at intervals of 1 hour, as part of a double-blind randomized trial. Effect of treatment was evaluated by measuring respiratory and heart rate, clinical scores based on the degree of retraction and wheezing, and oxygen saturation. Clinical assessment was repeated 30 minutes after each nebulization. A nasopharyngeal swab was obtained for detection of respiratory syncytial virus (VRS) antigens by immunofluorescence assay in all patients. RESULTS: Patients in the salbutamol group exhibited significantly greater improvement in respiratory rate (P = 0.01), accessory muscle score (P < 0.001) and wheezing score (P < 0.001). There was no significant difference in oxygen saturation between both groups. Infants treated with salbutamol exhibited a non-significant increase in heart rate after the three sprays; no other adverse effects were noted. VRS was identified in 78% of the children tested. CONCLUSIONS: Salbutamol is safe and effective in relieving the respiratory distress of young infants with acute bronchiolitis. Our study confirms previous observations that infants younger than six months of age respond as well as older children when given three doses of nebulized salbutamol. Responders could not be differentiated from non responders by personal or family histories of atopy and VRS isolation. A longitudinal study could establish a correlation between response to bronchodilator therapy and later development of asthma.

[Treatment with sustained theophylline release. Monitoring by salivary assay in children]. / Traitement par théophylline à libération prolongée. Surveillance par dosage salivaire chez l'enfant.

We have tested the possibility of replacing plasma assays by salivary assays of theophylline for the monitoring of sustained-release theophylline therapy in asthmatic children. In a first group of 40 children aged 7.2 +/- 3.3 years (mean +/- SD) treated with sustained-release theophylline in mean daily doses of 18.8 +/- 5 mg/kg, 77 plasma and saliva samples were taken simultaneously 6 hours after the morning dose (6 H). Saliva was collected after mouth-wash and stimulation with 10 mg of citric acid. Assays were performed using the EMIT method. Theophylline plasma concentrations (P) and salivary concentrations (S), both expressed as mumol/l, were found to correlate: P = 1.58 S + 8.7 (P less than 0.0001). In a second group of 33 children, 39 simultaneous samples were taken at 6 H. From the equation previously obtained the plasma concentration corresponding to each salivary concentration was calculated, and the calculated value was compared with the measured value. The difference between the two values was 7.1 +/- 9 mumol/l. On this basis, and because the method is non-invasive and painless, were are now using salivary assays (under strict conditions of collection and measurement) to verify the patients' compliance and to maintain or adjust dosage in asthmatic children.

[Food allergy: one only finds what one seeks]. / Allergie alimentaire: on ne trouve que ce qu'on recherche.

We report three observations of food allergy to Penicillium. A systematic approach has allowed the retention of the surprising diagnosis in the first observation that we met. For those following we were content with a diagnosis of strong suspicion, without making a provocation test. The indications of provocation tests are discussed. As in these observations, it is possible that certain food allergens which are considered as rare are in fact more frequent than those reported in the literature; when an allergy does not bother the patient, when exclusion of the food is easy, food allergy is "forgotten" and not reported to the physician.