Oral Immunotherapy for Food Allergy: A Spanish Guideline. Immunotherapy Egg and Milk Spanish Guide (ITEMS Guide). Part I: Cow Milk and Egg Oral Immunotherapy: Introduction, Methodology, Rationale, Current State, Indications, Contraindications, and Oral Immunotherapy Build-up Phase.

BACKGROUND AND OBJECTIVE: Cow milk and egg are the most frequent causes of food allergy in the first years of life. Oral immunotherapy (OIT) has been investigated as an alternative to avoidance diets. No clinical practice guidelines on the management of OIT with milk and egg are currently available. Objectives: To develop clinical guidelines for OIT based on available scientific evidence and the opinions of experts. METHODS: A review was made of studies published between 1984 and June 2016, doctoral theses published in Spain, summaries of communications at scientific meetings (SEAIC, SEICAP, EAACI, and AAAAI), and the consensus of opinion established by a group of experts from the scientific societies SEICAP and SEAIC. RESULTS: Recommendations were established regarding the indications, requirements and practical aspects of the different phases of OIT, as well as special protocols for patients at high risk of adverse reactions. CONCLUSIONS: Clinical practice guidelines based on the consensus reached between Spanish experts are presented for the management of OIT with milk and egg.

Oral Immunotherapy for Food Allergy: A Spanish Guideline. Egg and Milk Immunotherapy Spanish Guide (ITEMS GUIDE). Part II: Maintenance Phase of Cow Milk (CM) and Egg Oral Immunotherapy (OIT), Special Treatment Dosing Schedules. Models of Dosing Schedules of OIT With CM and Egg.

BACKGROUND AND OBJECTIVE: Cow milk and egg are the most frequent causes of food allergy in the first years of life. Oral immunotherapy (OIT) has been investigated as an alternative to avoidance diets. No clinical practice guidelines on the management of OIT with milk and egg are currently available. Objectives: To develop clinical guidelines for OIT based on available scientific evidence and the opinions of experts. METHODS: A review was made of studies published between 1984 and June 2016, doctoral theses published in Spain, summaries of communications at scientific meetings (SEAIC, SEICAP, EAACI, and AAAAI), and the consensus of opinion established by a group of experts from the scientific societies SEICAP and SEAIC. RESULTS: Recommendations were established regarding the indications, requirements and practical aspects of the different phases of OIT, as well as special protocols for patients at high risk of adverse reactions. CONCLUSIONS: Clinical practice guidelines based on the consensus reached between Spanish experts are presented for the management of OIT with milk and egg.

Oral immunotherapy for food allergy: A Spanish guideline. Egg and milk immunotherapy Spanish guide (ITEMS GUIDE). Part 2: Maintenance phase of cow milk (CM) and egg oral immunotherapy (OIT), special treatment dosing schedules. Models of dosing schedules of OIT with CM and EGG.

INTRODUCTION: Cow's milk and egg are the most frequent causes of food allergy in the first years of life. Treatments such as oral immunotherapy (OIT) have been investigated as an alternative to avoidance diets. No clinical practice guides on the management of OIT with milk and egg are currently available. OBJECTIVES: To develop a clinical guide on OIT based on the available scientific evidence and the opinions of experts. METHODS: A review was made of studies published in the period between 1984 and June 2016, Doctoral Theses published in Spain, and summaries of communications at congresses (SEAIC, SEICAP, EAACI, AAAAI), with evaluation of the opinion consensus established by a group of experts pertaining to the scientific societies SEICAP and SEAIC. RESULTS: Recommendations have been established regarding the indications, requirements and practical aspects of the different phases of OIT, as well as special protocols for patients at high risk of suffering adverse reactions. CONCLUSIONS: A clinical practice guide is presented for the management of OIT with milk and egg, based on the opinion consensus of Spanish experts.

Oral immunotherapy for food allergy: A Spanish guideline. Immunotherapy egg and milk Spanish guide (items guide). Part I: Cow milk and egg oral immunotherapy: Introduction, methodology, rationale, current state, indications contraindications and oral immunotherapy build-up phase.

INTRODUCTION: Cow's milk and egg are the most frequent causes of food allergy in the first years of life. Treatments such as oral immunotherapy (OIT) have been investigated as an alternative to avoidance diets. No clinical practice guides on the management of OIT with milk and egg are currently available. OBJECTIVES: To develop a clinical guide on OIT based on the available scientific evidence and the opinions of experts. METHODS: A review was made of studies published in the period between 1984 and June 2016, Doctoral Theses published in Spain, and summaries of communications at congresses (SEAIC, SEICAP, EAACI, AAAAI), with evaluation of the opinion consensus established by a group of experts pertaining to the scientific societies SEICAP and SEAIC. RESULTS: Recommendations have been established regarding the indications, requirements and practical aspects of the different phases of OIT, as well as special protocols for patients at high risk of suffering adverse reactions. CONCLUSIONS: A clinical practice guide is presented for the management of OIT with milk and egg, based on the opinion consensus of Spanish experts.

Cold urticaria and celiac disease.

Cold urticaria can be associated with blood and thyroid disorders, drugs, or infections. Celiac disease is an autoimmune enteropathy caused by permanent gluten intolerance. It is often associated with other autoimmune diseases, such as chronic idiopathic urticaria. Nevertheless, association with cold urticaria has not yet been described. A boy aged 3 years 8 months presented local urticaria-angioedema when exposed to cold temperatures. An ice cube test was positive and iron deficiency anemia was demonstrated. He later developed legume intolerance, rhinoconjunctivitis related to pollen sensitization, and asthma. Due to persistence of cold urticaria symptoms and refractory anemia, a test for immunoglobulin A autoantibodies to tissue transglutaminase and an intestinal biopsy were performed. Results of both tests were compatible with celiac disease.A study of human leukocyte antigen indicated a high risk phenotype (HLA, DR6/DR7; DQA 0501, 0201; DQB 0301, 0201). After 7 months of a gluten-free diet, the boy's anemia resolved and he is free of symptoms when exposed to cold. This is a first description of the possibility of an association between celiac disease and cold urticaria. A poor course of cold urticaria in the absence of evidence of another underlying condition should lead to suspicion of celiac disease.

Atopy and bronchial hyperresponsiveness in pure extrinsic childhood asthma.

Nonspecific bronchial hyperresponsiveness and atopy are considered risk factors in the development of asthma. Bronchial responsiveness to allergens could be the most important factor in extrinsic asthma. The trial was designed to investigate the role of specific and nonspecific bronchial responsiveness and atopy in a pure model of extrinsic asthma in children. One hundred and thirty-seven patients with pollen allergy were evaluated. Twenty children with allergy to grass pollen (Lolium perenne) alone, with symptoms only in the grass pollen season, were selected. Their score of symptoms, airway responsiveness to methacholine in and out of season, airway responsiveness to Lolium perenne out of season, and total and specific IgE were assessed. Twelve were male and eight female. Mild asthma was observed in 14, and moderate asthma in six. Age of onset of symptoms ranged from three to 13 years of age. Significant seasonal increase in airway responsiveness to methacholine was found (p = 0.002). Specific bronchial challenge test was positive in all patients. Lolium pernne PD20 ranged from 2.3 to 155.5 inhalation units. An inverse association between age of onset of symptoms and severity of asthma was shown (p = 0.001). Increase in nonspecific bronchial responsiveness was related to the appearance of symptoms during the spring, but it showed no relationship to the severity of symptoms. Severity of asthma during the spring correlated with the intensity of allergen airway responsiveness (p = 0.02). Levels of total and specific IgE were not related to the degree of specific or nonspecific airway responsiveness. Severity of extrinsic childhood asthma is determined by bronchial response to allergens. Bronchial hyperresponsiveness to methacholine during the spring can be the consequence of environmental exposure to allergens. The intensity of airway responsiveness to methacholine has no predictive value in the severity of pure extrinsic childhood asthma.

Evaluation of drug-related hypersensitivity reactions in children.

Patients with drug reactions are often referred to allergists for "allergy". Skin testing and clinical history seem to have a good negative predictive value, however, although drug challenge could be dangerous, it is the only way to confirm the diagnosis. We aimed to demonstrate that most children with a history of non-life-threatening drug reactions do not have a true drug allergy and examined the use of drug challenge in childhood. Patients with reactions were referred to our clinic by pediatricians. In 1 year, 354 reactions were studied in 239 children. Patients were classified according to their positive or negative history of drug allergy. Skin prick testing was done in all cases. Exclusion criteria for challenge included drug anaphylaxis, Stevens-Johnson syndrome, systemic reactions with severe concomitant illness, beta-inhibitor drug therapy or positive skin test to the implicated drug with a positive history. It was found that the beta-lactam antibiotics were involved in 50% of suspected reactions, aspirin in 10% and sulfonamides in 9%. Histories were considered positive only in 25%. Drug challenges confirmed only 4% of all reactions. It was concluded that drug challenge may be the gold standard for most childhood reactions that are considered to be allergic, non-life-threatening and drug-related. Only 4% of these suspected reactions were exclusively caused by drug allergy.

Asthma in children and ASA intolerance.

Intolerance to acetylsalicylic acid (ASA) in asthmatics has been widely studied in the adult population, and to a lesser extent in children. In the present study, we present 16 asthmatics between the ages of 2 and 14 suffering from asthma induced by ASA ingestion, and the clinical characteristics are compared with a population of asthmatic children with a negative challenge test. The following results were obtained: 1) in contrast to in adults, females are not predisposed to ASA intolerance in childhood, the male:female ratio being the usual 2:1 in infantile asthma; 2) ASA intolerance can appear at a very early age (in our series the youngest was 1 year old); 3) extrinsic asthmatics are the most commonly affected, and also children with exercise-induced asthma; 4) in extrinsic asthmatics with asthma attacks precipitated by ASA, sinusitis is more frequent than in extrinsic asthmatics with ASA tolerance; 5) polyposis is exceptional; 6) the presence of associated urticaria is frequent, and much greater than in adult ASA-intolerant asthmatics; and 7) the results of the challenge with NSAIDs are similar to those obtained in adult patients, which would indicate a common pathophysiological mechanism related to the capacity of these drugs to inhibit cyclooxygenase activity.

[Incidence of allergy to cow's milk protein in the first year of life and its effect on consumption of hydrolyzed formulae]. / Incidencia de alergia a proteínas de leche de vaca en el primer año de vida y su repercusión en el consumo de hidrolizados.

OBJECTIVES: The aims of this study were to determine the incidence of allergy to cow's milk protein in infants and the cost of treatment with hydrolyzed formulae in the Autonomous Community of Madrid. PATIENTS AND METHODS: Infants with suspected adverse reaction to cow's milk protein born between March 1, 2000 and February 28, 2001 within the catchment area covered by the pediatric services of Hospital La Paz were studied. The diagnostic algorithm of allergy to cow's milk protein of our department was used. The theoretical consumption of hydrolyzed formulae in the treatment of allergic infants was calculated and extrapolated to the Community of Madrid. RESULTS: There were 5367 live births in the above-mentioned catchment area. Adverse reaction to cow's milk protein was suspected in 185 infants. Allergy to cow's milk protein was confirmed in 101 (54 %). The incidence of allergy to cow's milk protein was 101/5356 (1.9 %). In the same period there were 57 078 live births in the Autonomous Community of Madrid. The number of infants that might be allergic in one year would be 1084. The cost of hydrolyzed formulae per infant and year would be 1,585.72 Euros. Thus, the cost of hydrolyzed formulae in the 1084 allergic infants would be 1,718,922.9 Euros; in the 923 in whom allergy was ruled out, the cost would be 1,463,621.8 Euros. CONCLUSIONS: The incidence of allergy to cow's milk protein in the first year of life is at least 1.9 %. The correct diagnosis allows us to rule out allergy to cow's milk protein in almost half of the cases, thus avoiding the use of unnecessary substitutive diets involving a high cost.

Tomato allergy in children and young adults: cross-reactivity with latex and potato.

BACKGROUND: Several studies have shown that allergy to natural rubber latex is associated with cross-reactivity to certain foods such as tomato and potato. The objective was to investigate the clinical and immunologic differences between a group of patients with clinical allergy to tomato and latex and another which had only clinical allergy to tomato. We also aimed to assess, in vitro, the relationship of tomato and latex allergens, which could explain the cross-reactivity. METHODS: Forty patients with histories of adverse reactions to tomato and IgE-mediated hypersensitivity were enrolled in the study. Tomato, latex, and potato components were analyzed by SDS-PAGE immunoblotting. CAP and immunoblot inhibition were used to study allergen cross-reactivity. RESULTS: Patients from group A had a mean age of 13.2 years, and in group B the mean age was 21.7 years. In group B, 9/10 patients belonged to the latex-fruits syndrome. All patients of both groups tolerated potato. Immunoblotting patterns obtained with patients' sera from pool A showed IgE-binding bands to tomato ranging from 44 to 46 kDa and a triple band at 67 kDa. For latex, there was a strong binding at 44 kDa, and potato showed a strong band of 44 kDa and a 67-kDa triple band. In pool B, the binding to the band of 44 kDa in latex and tomato was more intense than in pool A. In pool A, immunoblot inhibition with potato allergen showed an intense inhibition of the three allergens (potato, latex, and tomato); with latex, inhibition was partial and with tomato, a complete inhibition of tomato and latex was observed, and a partial inhibition of potato. In pool B, the inhibition pattern followed a similar tendency to pool A. The CAP inhibition confirmed the high rate of cross-reactivity between tomato, potato, and latex. CONCLUSIONS: In our study, tomato, potato, and latex showed a common band of 44-46 kDa probably corresponding to patatin. This protein could be implicated in the high cross-reactivity between tomato, latex, and potato observed in the immunoblot and CAP inhibition.

Allergy to lentils in Mediterranean pediatric patients.

BACKGROUND: Peanuts and soybeans are the major legumes involved in human food allergy; however, scarce data exist on adverse reactions to other temperate legumes, such as lentils. OBJECTIVE: The purpose of this study was to identify patients who are allergic to lentils, to assess clinical features and other associated food allergies, and to characterize allergens in lentil extract. METHODS: Twenty-two children each with a history of adverse reactions to lentils were enrolled in the study. The diagnosis of lentil allergy was based on food challenges or a convincing history of anaphylaxis, with positive skin tests and/or specific serum IgE to lentils. Lentil components were characterized by SDS-PAGE immunoblotting. RESULTS: Twenty of 22 subjects had symptomatic allergy to lentils at the diagnostic time. The most frequent symptoms were oropharyngeal symptoms (40%) and acute urticaria (30%); 3 patients also reported symptoms when they were exposed to steam from cooked lentils. In 18 patients, symptoms after lentil ingestion started under 4 years of age (median, 2.7 years). Nine patients had allergic reactions to other legumes: chick peas (6 patients), peas (2 patients), and green beans (1 patient). Immunoblotting patterns obtained with patients' sera showed IgE-binding bands ranging from 14 to 84 kd. Five sera recognized 9 or more IgE-binding bands, and more than 50% of patients who were tested have specific IgE antibodies to 7 components in lentil extract. CONCLUSION: Allergic reactions to lentils started early in life, usually below 4 years of age; oropharyngeal symptoms and acute urticaria were the most common symptoms through ingestion, and symptomatic reactivity to chick peas is frequently associated.

Evaluation of an extensively hydrolyzed casein-whey protein formula in immediate cow's milk protein hypersensitivity.

BACKGROUND: Hydrolysate formulas are safe for most infants who are allergic to cow's milk. The purpose of this study was to assess the clinical tolerance and safety of an extensively hydrolyzed casein-whey protein formula in a homogeneous group of patients with immediate cow's milk hypersensitivity. METHODS: The study population consisted of 33 infants in whom immediate cow's milk protein allergy had been diagnosed by clinical data, evidence of specific immunoglobulin E antibodies, and positive results in a controlled challenge test with cow's milk proteins. RESULTS: The hydrolysate was well tolerated in 31 of the 33 patients, which represented a 94% effectiveness. Using 95% confidence intervals generated for a binomial outcome (reaction-no reaction), the casein-whey protein formula is tolerated by 84.4% to 99% of infants with immediate immunoglobulinE-mediated cow's milk protein allergy. These figures are in the range of values recommended for this type of product. CONCLUSIONS: This extensively hydrolyzed casein-whey protein formula is generally safe to feed children with immediate hypersensitivity to cow's milk. However. it is advisable that the first intakes be given under direct medical supervision, in that the occurrence of adverse reactions in highly sensitive infants cannot be unequivocally excluded.

Specific IgE levels in the diagnosis of immediate hypersensitivity to cows' milk protein in the infant.

BACKGROUND: A milk-free diet with substitute formula should be established when immediate symptomatic hypersensitivity to cows' milk protein (CMP) is diagnosed, and therefore an accurate diagnosis is very important. OBJECTIVE: This study aims to find the optimal cutoff values for specific IgE antibody levels that discriminate between allergic and tolerant infants by using cows' milk and its principal proteins as allergens. METHODS: A prospective study was carried out on 170 patients under 1 year old (mean, 4.8 months). These patients were seen consecutively over a 4-year period in our outpatient clinic and for the first time because of a reaction suggesting immediate hypersensitivity after ingestion of cows' milk formula. A clinical history, prick test with cows' milk and its proteins (alpha-lact-albumin, beta-lactoglobulin, and casein), determination of specific IgE antibodies with the CAP system FEIA for the same allergens as for the prick test, and a challenge test according to the diagnostic protocol were performed in all of the children. A study of validity of the prick test (cutoff point, 3 mm) and CAP system by using different cutoff points in the specific IgE values for cows' milk and its proteins were also analyzed. RESULTS: Prevalence of immediate symptomatic hypersensitivity to CMP in this study was 44%. When both the whole milk and its principal milk proteins were used in the prick test, the negative predictive value was very high, and a negative value excluded allergy in 97% of the patients. When the different cutoff points of the specific IgE for milk were analyzed, 2.5 KU(A)/L had a positive predictive value of 90% and 5 KU(A)/L had a positive predictive value of 95%. CONCLUSIONS: When diagnosing immediate hypersensitivity to CMP in infants, negative skin test responses exclude allergy in most of the patients. If the prick test response is positive, specific IgE levels for cows' milk may be helpful. If these values are 2.5 KU(A)/L or greater, the challenge test should not be performed because of its high positive predictive value (90%).

Exercise-induced anaphylactic reaction to hazelnut.

Reproducible, exercise-induced anaphylactic reactions occur in some patients only after certain foods have been eaten before exercise. We describe a patient in whom hazelnuts were a triggering factor for exercise-induced anaphylaxis. Skin tests and RAST were positive for nuts and grass and weed pollen. The exercise challenge test after hazelnut ingestion was positive. Food hypersensitivity should be investigated in all cases of exercise-induced anaphylaxis.

Hypersensitivity to mercuric fluorescein compounds.

The mercurial compounds are known to be a common cause of allergic contact dermatitis. Immediate hypersensitivity is rarely induced by mercurial organic derivatives. However, none of the published cases showed both immediate and delayed hypersensitivity as was the case of one of our two patients. A boy and a woman experienced urticaria and anaphylaxis, respectively after topical application of Merchromine (Merbromine). We were able to demonstrate immediate hypersensitivity in both patients to mercuric fluorescein compounds by skin test and histamine liberation. In addition, the child but not the woman, showed delayed hypersensitivity to mercurial compounds.

[Asthma and gastroesophageal reflux. Outcome of asthma after longterm medical treatment of the reflux]. / Asma y reflujo gastroesofágico. Resultados del asma con tratamiento médico prolongado del reflujo.

Over one half of the cases of chronic severe childhood asthma, refractory to conventional therapy and without other over aetiology, are associated to gastroesophageal reflux (GER). The aetiopathogenic role of GER in asthma is uncertain, and is only confirmed when therapy of the former induces evident improvement of the latter. We have instituted medical antireflux therapy over two years in 17 patients (17.6%) became asymptomatic after less than three months of therapy, and a further four (23.5%) by the sixth month. Seven patients showed clinical improvement by the third month (41%) and even a greater one by the sixth month, only very slight symptoms persisting thereafter. In three cases (17.6%) there was no improvement after two years of outcome of asthma and the persistence or not of pathological between the outcome of asthma and the persistence or not of pathological 24-hour pHmetry. On the contrary. macroscopic oesophagitis disappeared in the cases of asthma with good outcome, but persisted in all the cases who remained symptomatic. In conclusion, we consider that medical management of GER associated to asthma should be maintained for at least six months (if the clinical course so permits) before considering a surgical indication.