Clinical Pattern and Acute and Long-term Management of Hereditary Angioedema Due to C1-Esterase Inhibitor Deficiency.

BACKGROUND: Hereditary angioedema due to C1-esterase inhibitor deficiency (HAE-C1-INH) is a life-threatening disease. OBJECTIVES: To describe the clinical characteristics and management of patients with HAE-C1-INH during routine clinical practice. METHODS: An observational, retrospective study was performed in patients with HAE-C1-INH. Demographic, clinical, and analytical data were collected from 2 periods: period A (October 2009-September 2010) and period B (October 2007-September 2009). RESULTS: We studied 112 patients with HAE-C1-INH (57.1% females). Age at onset of symptoms was 14.4 years (lower in patients who had experienced attacks in the previous year). In period B (n=87), 62.1% of patients presented at least 1 edema attack (median, 3.5 attacks/patient/2 years), and 19.1% of attacks were treated. In period A (n=77), 58.4% of patients were on maintenance therapy. Stanozolol was the most widely used drug (48.9%), with a mean weekly dose of 6.7 mg. At least 1 attack was recorded in 72.7% of patients (median, 3.0 attacks/patient/year), and 31.5% of the attacks were treated. Treatment of acute attacks increased by 12.4%. CONCLUSION: Age at onset of symptoms is associated with clinical expression of disease. The higher age at onset of symptoms, the fewer number of attacks per patient and year, and the lower dose of attenuated androgens necessary to control the disease than in other series lead us to hypothesize that HAE-C1-INH could have a less severe expression in Spain. Acute attacks seem to be treated increasingly often.

The predictive value of specific immunoglobulin E levels in serum for the outcome of the development of tolerance in cow's milk allergy.

BACKGROUND: Immunoglobulin E-mediated allergy to cow's milk protein (CMP) tends to subside over years of follow-up. The gold standard for detecting such allergy has been the oral challenge test. The development of some other test for determining the correct timing of the oral challenge test would avoid unnecessary patient discomfort. The aim of this study was to determine whether monitoring cow's milk (CM) specific IgE levels over time can be used as a predictor for determining when patients develop clinical tolerance. METHODS: A prospective 4-year follow-up study was made of 170 patients with IgE-mediated allergy to CMP, involving periodic evaluations (12, 18, 24, 36 and 48 months) with the determination of casein and CM specific IgE on each visit, along with CM challenge testing. ROC curves were used to analyse the sensitivity, specificity and predictive values of the casein and CM specific IgE levels versus the challenge test outcomes at the different moments of follow-up. RESULTS: In the course of follow-up, 140 infants (82 %) became tolerant. Specific IgE levels to CM: 2.58, 2.5, 2.7, 2.26, 5 kU(A)/l and to casein: 0.97, 1.22, 3, 2.39, 2.73 kU(A)/l, respectively, predicted clinical reactivity (greatest diagnostic efficiency values) at the different analysed moments of follow-up (12, 18, 24, 36 and 48 months). CONCLUSIONS: Quantification of CMP specific IgE is a useful test for diagnosing symptomatic allergy to CM in the paediatric population, and could eliminate the need to perform oral challenges tests in a significant number of children.

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.

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.

[Prevention of food allergy]. / Prevención de la alergia alimentaria.

The occurrence of allergic diseases depends on genetic and environmental factors. Genetic factors determine individual risk and these persons should undergo early detection. However, the methods currently available (mainly clinical history and IgE in umbilical cord blood) have poor predictive value so their use in the general population is not practical. In contrast, the feeding habits of newborns and infants can influence the development of food allergies in children at risk. Therefore, several modes of action have been proposed, based mainly on prolonging breast-feeding (with the mother avoiding allergenic foods) and delaying the introduction of complementary foods considered to be a risk. Use of cow milk protein hydrolysates may have a preventive effect similar to that of breast-feeding, but their administration is not problem-free. The preventive effect of partial hydrolysates or soybean formulas is even more questionable.

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.

IgE crossreactivity between mugwort pollen (Artemisia vulgaris) and hazelnut (Abellana nux) in sera from patients with sensitivity to both extracts.

BACKGROUND: An association between sensitization to Compositae pollens and hypersensitivity to hazelnut has been previously described. There is no previous in vitro study about crossreactivity between mugwort pollen and hazelnut. OBJECTIVES: To study mugwort pollen and hazelnut allergens and to assess if there is IgE crossreactivity between mugwort pollen and hazelnut. METHODS: A serum pool formed by 28 individual sera with specific IgE to mugwort pollen and hazelnut was used to investigate IgE crossreactivity. RAST-inhibition, SDS-PAGE/IEF immunoblotting inhibition assays were performed by preincubation of the sera with mugwort pollen and hazelnut. RESULTS: RAST to hazelnut was inhibited up to 63% by mugwort pollen, but the mugwort pollen RAST was only inhibited up to 36% by hazelnut. In SDS-PAGE immunoblotting mugwort pollen showed nine allergens ranging from <16 to 65 kDa and hazelnut had four main allergens: 42 kDa, 17 kDa and <16 kDa (two bands). In the SDS-PAGE immunoblotting inhibition hazelnut partially inhibited all the mugwort pollen bands, except that with 19kDa, whereas mugwort pollen produced a nearly total inhibition of all the hazelnut allergens. In isoelectrofocusing immunoblotting mugwort pollen had two groups of allergens: pI 7.5-8.5 and pI 3.5-5.2 and hazelnut one group of allergens: pI 5.2-5.8. In the isoelectrofocusing immunoblotting inhibition hazelnut produced a partial inhibition of all the bands of mugwort pollen and mugwort pollen partially inhibited all the allergenic bands of hazelnut. CONCLUSIONS: The RAST and SDS-PAGE/IEF immunoblotting inhibition results provide evidence of IgE cross reactivity between mugwort pollen and hazelnut allergens. The inhibition of hazelnut by mugwort pollen is higher than the inhibition of mugwort pollen by hazelnut in both RAST inhibition and SDS-PAGE immunoblotting inhibition. These results suggest that mugwort pollen allergens would behave as primary immunogens in the association between sensitivity to mugwort pollen and hazelnut.

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.

Nonspecific bronchial hyperresponsiveness and development of asthma in children with hay fever.

It has been suggested that patients with allergic rhinitis who present nonspecific bronchial hyperresponsiveness (BHR) are those most likely to develop asthma. Therefore, a study was conducted in children with rhinoconjunctivitis to ascertain whether BHR to methacholine might predict the development of asthma in these patients. Fifteen patients with hay fever and no previous symptoms of asthma were selected. All underwent clinical symptom tests and methacholine tests, during the pollen season in the 4 consecutive years following the start of the study. At the end of this period, 5 patients had developed asthma. It may thus be affirmed that, in this group, neither the presence nor the degree of previous BHR was useful for predicting which patients would later develop asthma.

[Relationship between the degree of specific IgE sensitization to food allergens and the appearance of clinical manifestations]. / Relación entre el grado de sensibilización IgE específica a alérgenos alimentarios y la aparición de manifestaciones clínicas.

AIMS: To assess distribution and correlation between serum concentrations of specific IgE for food allergens and clinical symptoms after exposure. PATIENTS AND METHODS: Four hundred and thirty seven allergic children with 1097 sensitizations to food allergens, confirmed by prick-test and/or Phadezym RAST, were evaluated. From these sensitizations, 558 were associated to clinical symptoms after food intake (SFS), demonstrated by clinical history and/or open oral provocation, and 539 were asymptomatic food sensitizations (AFS). RESULTS: In these patients, the most frequent values of serum specific IgE (44%) were found in the 0.7 and 3.5 PRU/ml range, although in 18% of the cases no specific IgE was detected. Some differences in this distribution exist for different groups of food allergen, with predominance of negative results for food of the rosaceae group. On the contrary, specific IgE values higher than 17.5 PRU/ml are predominant for fish allergens. There is a statistically significant correlation (chi 2 p < 0.001) between anti-food allergen specific IgE concentrations and the clinical symptoms occurred after intake, so the serum specific IgE values between 0.35 and 3.5 PRU/ml are present with higher frequency in the AFS, while values higher than 17.5 PRU/ml are found with a statistically significant higher frequency in the SFS. When different food groups are evaluated separately, some mild differences exist. CONCLUSIONS: A statistically significant correlation between anti-food allergen specific IgE concentrations and the clinical symptoms ocurred after intake. Therefore, specific IgE quantitative assessment and its relationship to clinical symptoms may be of great interest in the management of food 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.

[Allergic drug reactions in children]. / Reacciones alérgicas a medicamentos en niños.

We present a retrospective study of allergic drug reactions seen in our pediatric allergy consulting room during the last 6 years. During this time, 840 patients were examined for suspected adverse drug reactions. Drug allergy was confirmed in 72 cases (8.5%). Of these cases, 29 (40.2%) were considered to be IgE mediated, or immediate hypersensitivity reactions. We have not found significant differences with regards to age, sex, atopic family history or atopia between patients with IgE mediated reactions compared to patients with allergic drug reactions of different mechanisms or to patients without drug allergies. Sulfonamides, streptomycin, beta-lactam and analgesics were the drugs most frequently involved in immediate type reactions. Among non-immediate reactions, fixed eruption by sulfonamides and contact dermatitis due to Mercurochrome were the most frequent.