Eliciting doses of positive challenge test in cow's milk allergy are related to cow's milk specific IgE levels.

BACKGROUND: Ingestion of small amounts of cow's milk (CM) can elicit adverse reactions in patients with IgE-mediated CM allergy. Knowing the dose eliciting allergic reactions and the factors affecting it can be of great help in avoiding these reactions. OBJECTIVE: To analyse the eliciting doses of positive challenge test in patients with CM allergy and to determine its association with the level of CM specific IgE. METHODS: Ninety-eight positive challenge tests in 56 children, median age of 11 months (3-80) with IgE-mediated CM allergy were retrospectively analysed. Open oral challenge tests were carried out by gradually increasing doses of milk (2-100 ml). The relationship between challenge test doses and CM specific IgE levels were studied. RESULTS: 18 % of the challenge tests were positive with 2 ml, 24 % with doses between 5 and 10 ml, and the other 58 % with doses between 25 and 100 ml. An inverse association between the doses of the positive challenge test and the level of CM specific- IgE was found, 13.9 kU/L (0.54-> 100 kU/L) when the challenge test was positive with the smaller dose (2 ml); and 1.73 kU/L (< 0.35-76.4 kU/L) with doses above 2 ml (p = 0.0001). The median age of the patients was 13 months (6-49) when the challenge test was positive with 2 ml vs 9 months (3-80) with doses above 2 ml (p = 0.048). CONCLUSION: The CM specific IgE level and patient's age should be considered in the assessment of the eliciting doses of positive challenge test in CM allergy.

Cow's milk-specific immunoglobulin E levels as predictors of clinical reactivity in the follow-up of the cow's milk allergy infants.

BACKGROUND: IgE-mediated cow's milk proteins (CMPs) allergy shows a tendency to disappear with age. The sooner tolerance is detected, the earlier the substitute diets can be suspended and the quicker family emotional hardship is alleviated. OBJECTIVE: To analyse the specific IgE levels to cow's milk and its proteins, which help to separate tolerant from no tolerant children in the follow-up of infants with allergy to cow's milk. PATIENTS AND METHODS: Sixty-six infants diagnosed with IgE-mediated allergy to CMPs were included in this prospective follow-up study. Periodic reassessments were carried out every 6 months until they were 2-years old and then, annually, until tolerance arose or until the last reassessment in which tolerance had not been achieved. Non-tolerant infants were followed, at least, for a period of 3 years. In each visit, the same skin tests and determination of specific IgE (CAP System FEIA) for milk and its proteins were carried out. The open challenge test was repeated unless a clear transgression to milk, which came to be positive, had taken place within the previous 3 months in each of the follow-up visits. Specific IgE levels to milk and its proteins, in different moments of the follow-up were analysed by means of the receiver-operating characteristic curve to predict clinical reactivity. RESULTS: Throughout the follow-up 45 (68%) infants became tolerant. The follow-up mean for tolerant infants was 21.2 months whereas for non-tolerant infants it was 58 months. The specific IgE levels which were predictors of the clinical reactivity (positive predictive value (PPV)> or =90%), grew as the age of the infants increased: 1.5, 6 and 14 kU(A)/L for milk in the age range 13-18 and 19-24 months and in the third year, respectively. Specific IgE levels to casein: 0.6, 3 and 5 kU(A)/L, respectively, predicted clinical reactivity (PPV> or =90%) in the different analysed moments of the follow-up. The cut-off points: 2.7, 9 and 24 kU(A)/L for milk and 2, 4.2 and 9 kU(A)/L for casein, respectively, predicted clinical reactivity with an accuracy > or =95% corresponding to a specificity of 90%. CONCLUSIONS: Monitorization of specific IgE concentration for milk and casein by means of the CAP system in allergic children to CMPs allows us to predict, to a high degree of probability, clinical reactivity. Age factor must be taken into account to evaluate the specific IgE levels which are predictors of tolerance or clinical reactivity.

[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.

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

Objetivos: Cálculo de la incidencia de alergia a proteínas de leche de vaca (APLV) en el lactante y coste del tratamiento con hidrolizados de leche de vaca en la comunidad de Madrid. Pacientes y métodos Lactantes con sospecha de APLV nacidos entre el 1 de marzo de 2000 y el 28 de febrero de 2001 en el Hospital La Paz pertenecientes a las áreas que atiende el Hospital Infantil. Se les aplicó el algoritmo diagnóstico de APLV del servicio. Se realizó el cálculo teórico del consumo de hidrolizados utilizados en el tratamiento de los APLV y se extrapoló a la comunidad de Madrid. Resultados Nacidos vivos en el Hospital La Paz pertenecientes a las áreas citadas: 5.356 niños. Consultaron por sospecha fundada de APLV: 185 niños. Se diagnosticaron como alérgicos a PLV a 101 (54 per cent). La incidencia calculada de APLV fue de: 101/5.356: 1,9 per cent. Nacidos en la comunidad de Madrid en el mismo período: 57.078 niños. El número de posibles APLV en un año sería de 1.084. El cálculo aproximado de consumo de hidrolizados en el primer año de vida por niño, supone un coste de 1.585,72 3. El gasto de hidrolizados en los 1.084 alérgicos en la comunidad de Madrid sería de 1.718.922,9 3. El gasto de los 923 niños en los que se descartó alergia supondría 1.463.621,8 3.Conclusiones La incidencia de APLV en el primer año de vida en nuestro medio es de, al menos, 1,9 per cent. El diagnóstico correcto permite descartar APLV en casi la mitad de los casos, evitando someter al lactante a dietas innecesarias y que suponen un elevado coste (AU)

Validity of specific IgE antibodies in children with egg allergy.

BACKGROUND: The demonstration of specific IgE antibodies to egg supports the existence of allergy to this food, but a correct diagnosis can only be obtained after a challenge test. Several studies have assessed different cut-off points in the level of these antibodies as predictors of clinical reactivity. OBJECTIVE: Validation of the specific IgE antibodies measured by the CAP System Fluorescence enzyme immunoassay (FEIA) technique in the diagnosis of egg allergy in children under 2 years of age. METHODS: A prospective study of 81 children with suspected egg allergy was performed. Specific IgE antibodies was quantified for egg white, egg yolk, ovoalbumin and ovomucoid. The diagnostic challenge test was carried out following the previously established criteria. The validity of the specific IgE antibodies was analysed using children with a negative diagnostic challenge test as control group. RESULTS: The prevalence of egg allergy in the group studied was 79% and egg white was the allergen that showed the greatest diagnostic efficacy. The sensitivity and positive predictive value of the prick test and of the CAP to egg white were excellent and the specificity and the negative predictive value had lower values. A level of > or = 0.35 KU(A)/L for specific IgE antibodies to egg white predicted the existence of reaction in 94% of the cases. CONCLUSIONS: Quantification of the specific IgE antibodies to egg white is useful in the diagnosis of egg allergy. In children under 2 years of age with a background of immediate hypersensitivity after egg ingestion and presence of specific IgE antibodies to egg white of > or = 0.35 KU(A)/L, diagnostic challenge test is not necessary to establish the diagnosis of allergy to this food.

Syndrome auriculotemporal.

Two cases of auriculotemporal syndrome are presented in two male children that began in the first years of life to present reactions of linear erythema itinerary on the cheeks after eating several foods. The allergologic study with these foods was negative, reproducing the clinical picture after their ingestion.

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%).

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.

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.

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.

Peculiarities of egg allergy in children with bird protein sensitization.

BACKGROUND: Hen's egg is frequently implicated in food allergy in children. Sometimes this allergy is associated with bird protein sensitization. OBJECTIVE: A study was conducted to establish the possible role of bird protein sensitization in the clinical picture and evolution of egg allergy in patients with both egg and bird sensitization. METHODS: Epidemiologic and clinical characteristics and the results of allergic study of 27 patients with both egg and bird allergy were compared with those of a control group of 19 egg-allergic patients without bird protein sensitization. All patients were evaluated clinically each year during the 4 years subsequent to the beginning of the study or until clinical tolerance to egg was achieved. RESULTS: Patients with bird sensitization had more frequent digestive and respiratory symptoms related to egg ingestion compared with the control group. At the end of follow-up. 15% of the bird sensitized patients and 58% of the controls tolerated egg. Egg yolk sensitization was the major sensitization in bird-sensitized patients. CONCLUSION: It is necessary to exclude sensitization to bird proteins in egg-allergic patients, mainly when they show respiratory or digestive symptoms after egg ingestion, the egg allergy persists over a long period of time or egg yolk sensitization is strong.

Egg white-specific IgE level as a tolerance marker in the follow up of egg allergy.

Forty patients with symptomatic immediate hypersensitvity to egg who did not have atopic dermatitis were evaluated to determine if they continued to remain clinically symptomatic. Each had specific IgE in vitro and positive prick-test to egg. All patients were on an egg elimination diet. During the follow-up an open egg rechallenge was performed along with a determination of egg white-specific IgE by CAP System. The egg white-specific IgE values were higher in the positive challenge group than in the negative one (p < 0.01, Mann-Whitney Test). There was a direct proportional relationship between the levels of egg white-specific IgE and the likelihood of positive challenge. Specific IgE values above 1.20 KUA/L could be adequate grounds for delaying the follow-up of egg challenge.

Analysis of cross-reactivity between sunflower pollen and other pollens of the Compositae family.

The sera of 20 patients with Compositae pollen allergy were investigated for the presence of IgE antibodies reacting against sunflower pollen by means of RAST and immunoblotting studies. Thirteen IgE-binding bands were detected with molecular weights ranging from 14.4 to 94 kd. Two of these bands, with molecular weights of 24 and 25 kd, contained major allergens that reacted strongly with 100% (24 kd) and 95% (25 kd) of the sera, respectively. Cross-reactivity between sunflower and other Compositae pollens (mugwort, marguerite, dandelion, golden rod, and short ragweed) was revealed by RAST and immunoblotting inhibition experiments. Mugwort pollen exhibited the greatest degree of allergenic homology (cross-reactivity) with sunflower pollen, whereas at the other end of the spectrum, short ragweed showed less cross-reactive epitopes.

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.

Urticaria induced by caffeine.

Caffeine has rarely been reported as the cause of allergic reactions. We describe a 10-year-old child who developed urticaria after the intake of coffee and cola beverages. The prick test and the oral challenge test with caffeine were both positive. Nevertheless, the oral challenge test with theophylline, another methylxanthine, was negative.