Effectiveness of allergy testing in milk induced eosinophilic esophagitis. Description and follow-up of patients.

INTRODUCTION: Eosinophilic esophagitis (EoE) is a chronic, local immune-mediated esophageal disease that has been on the increase lately. There is currently enough evidence to conclude that EoE is an allergic disorder triggered by food allergens, with cow's milk (CM) being the most frequent. Dietary intervention is the first-line approach. This study aimed to assess the clinical characteristics, the diagnostic method, and the prognosis of patients whose culprit food was CM, as opposed to other triggers. METHODS: Children with EoE evaluated in our pediatric Allergy Department were retrospectively studied from 2004 to 2017. We collected clinical variables, diagnostic protocol, treatment, and follow-up data. We compared patients whose culprit food was CM and patients with EoE due to other causative agents. RESULTS: We analyzed 31 children with EoE and found the causative food to be cow's milk in 14 (45%). Clinical characteristics were similar in patients with EoE due to milk or any other cause. Eight of 14 patients with milk-induced EoE (57.14%) presented positive skin prick test results against cow's milk. All patients had positive IgE against cow's milk. None of the patients had any other food as the trigger. The median follow-up was 2.68 years (6 months to 9 years) with initial remission of 100%. CONCLUSION: Testing-based elimination diets effectively treated all of the patients with milk-induced EoE. The advantage of this diagnostic protocol is that it required a mean of only two foods to be tested, significantly smaller number than in empiric diets.

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.

Is Microarray Analysis Really Useful and Sufficient to Diagnose Nut Allergy in the Mediterranean Area?

BACKGROUND: Component-based diagnosis on multiplex platforms is widely used in food allergy but its clinical performance has not been evaluated in nut allergy. OBJECTIVE: To assess the diagnostic performance of a commercial protein microarray in the determination of specific IgE (sIgE) in peanut, hazelnut, and walnut allergy. METHODS: sIgE was measured in 36 peanut-allergic, 36 hazelnut-allergic, and 44 walnut-allergic patients by ISAC 112, and subsequently, sIgE against available components was determined by ImmunoCAP in patients with negative ISAC results. ImmunoCAP was also used to measure sIgE to Ara h 9, Cora 8, and Jug r 3 in a subgroup of lipid transfer protein (LTP)-sensitized nut-allergic patients (positive skin prick test to LTP-enriched extract). sIgE levels by ImmunoCAP were compared with ISAC ranges. RESULTS: Most peanut-, hazelnut-, and walnut-allergic patients were sensitized to the corresponding nut LTP (Ara h 9, 66.7%; Cor a 8, 80.5%; Jug r 3, 84% respectively). However, ISAC did not detect sIgE in 33.3% of peanut-allergic patients, 13.9% of hazelnut-allergic patients, or 13.6% of walnut-allergic patients. sIgE determination by ImmunoCAP detected sensitization to Ara h 9, Cor a 8, and Jug r 3 in, respectively, 61.5% of peanut-allergic patients, 60% of hazelnut-allergic patients, and 88.3% of walnut-allergic patients with negative ISAC results. In the subgroup of peach LTP-sensitized patients, Ara h 9 sIgE was detected in more cases by ImmunoCAP than by ISAC (94.4% vs 72.2%, P < .05). Similar rates of Cora 8 and Jug r 3 sensitization were detected by both techniques. CONCLUSIONS: The diagnostic performance of ISAC was adequate for hazelnut and walnut allergy but not for peanut allergy. sIgE sensitivity against Ara h 9 in ISAC needs to be improved.

Is the ISAC 112 Microarray Useful in the Diagnosis of Pollinosis in Spain?

BACKGROUND: Multiple sensitization is frequent among pollen-allergic patients. The goal of this study was to determine the diagnostic accuracy of the ImmunoCAP ISAC 112 (ISAC112) microarray in allergy to pollen from several taxa and its clinical utility in a Spanish population. METHODS: Specific IgE was determined in 390 pollen-allergic patients using the ISAC112 microarray. Diagnostic accuracy (sensitivity, specificity, predictive values, and area under the ROC curve) was calculated for the diagnosis of allergy to pollen from grass (n=49), cypress (n=75), olive tree (n=33), plane tree (n=63), and pellitory of the wall (n=17) and compared with that of the singleplex ImmunoCAP immunoassay. RESULTS: The sensitivity of the ISAC112 microarray ranged from 68.2% for allergy to plane tree pollen to 93.9% for allergy to grass pollen. The specificity was >90%. The AUC for the diagnosis of allergy to plane tree pollen was 0.798, whereas the AUC for the remaining cases was ≥0.876. The accuracy of ISAC112 was higher than that of ImmunoCAP for plane tree pollen and similar for the remaining pollens. The frequency of sensitization to most species-specific allergenic components and profilins varied between the different geographical regions studied. A total of 73% of pollen-allergic patients were sensitized to species-specific components of more than 1 pollen type. CONCLUSIONS: The ISAC112 microarray is an accurate tool for the diagnosis of allergy to pollen from grass, cypress, olive tree, plane tree, and pellitory of the wall. The features of the ISAC112 microarray are similar or superior (in the case of plane tree pollen) to those of ImmunoCAP. This microarray is particularly useful for the etiologic diagnosis of pollinosis in patients sensitized to multiple pollen species whose pollination periods overlap.

Immunochemical Analysis of the Specificites of IgE Antibodies Directed to Benzylpenicilloyl.

The contribution that the different parts of the benzylpenicillin (BP) molecule made to the antigen-binding site was studied using human IgE sera specific to the benzylpenicilloyl (BPO) determinant. Radioallergosorbent test inhibition studies were made using in the solid phase BPO and in the fluid phase BP butylamine, 6-amino-penicillanic acid-butylamine, thiazolidine, and phenyl-acetic acid. The results indicate that the whole BPO structure was required for optimal inhibition in all sera studied and that important differences were obtained comparing these results with those obtained with the different parts of BP. These structures contributed to a different degree to the constitution of the antigenic determinant.

Determination of IgE in the serum of patients with allergic reactions to four species of fish-parasite anisakids.

This study investigates cross-reactions between somatic and metabolic antigens of various anisakids in the serum of patients with allergic processes. Twenty patients with allergic reactions after eating fish were studied using the skin-prick test for sensitivity to four species of anisakids. IgE was also determined, by blotting, in the serum of these patients when confronted with somatic and metabolic antigens of Anisakis simplex s.l. and Hysterothylacium aduncum, and somatic antigens of A. physeteris and H. fabri. The results obtained with both techniques basically agree, the following facts being of particular note: four patients presented specific IgE for A. simplex s.l. and 1 for Hysterothylacium sp. only, eight patients presented cosensitivity for A. simplex s.l. and A. physeteris, two for A. simplex s.l. and Hysterothylacium sp., one for A. physeteris and Hysterothylacium sp., and two for A. simplex s.l., A. physeteris and Hysterothylacium sp. Given the results obtained, it should be considered that other species of fish-parasite anisakids, apart from A. simplex s.l., may be involved in the allergic reactions presented by a large number of patients.

The presence of latex can induce false-positive skin tests in subjects tested with penicillin determinants.

Latex allergens are ubiquitous, and exposure may occur from different sources in the medical environment and in daily life. The observation that subjects with latex allergy were skin test positive to major and minor determinants of penicillins led our group to carry out an investigation to try to explain these findings. A group of 20 subjects with a history of allergy to latex and with positive skin tests for, but good tolerance of, penicillins was studied. The presence of latex contaminants was studied by RAST and RAST inhibition. Sixteen of the subjects were positive to at least one of the penicillin determinants used, and 14 (87%) of these were positive to at least two determinants. Repetition of skin tests using the container without a stopper changed the skin test results to negative in almost all cases, indicating that some trace contaminants had still been present. RAST-inhibition studies showed that in all penicillin determinants there were trace amounts of latex allergens varying between 3 and 0.03 micrograms/ml. These results indicate that skin tests with penicillin in subjects allergic to latex may give false-positive results and lead to such patients being falsely diagnosed as allergic to betalactams when penicillins are stored in containers with rubber stoppers.

Angioedema and IgE antibodies to aspirin: a case report.

We present a case of a patient who developed two episodes of angioedema after taking acetylsalicylic acid orally. Specific IgE antibodies to acetylsalicylic human serum albumin (ASA-HSA) were found. A control group of 37 patients with aspirin intolerance was studied and evidence of specific IgE antibodies was not found. The follow-up of this case shows that in a short period of time the level of specific IgE antibody decreases to undetectable levels similar to the negative control population.

Immediate allergic reactions to amoxicillin.

A large group of patients with suspected allergic reactions to beta-lactam antibiotics was evaluated. A detailed clinical history, together with skin tests, RAST (radioallergosorbent test), and controlled challenge tests, was used to establish whether patients allergic to beta-lactam antibiotics had selective immediate allergic responses to amoxicillin (AX) or were cross-reacting with other penicillin derivatives. Skin tests were performed with benzylpenicilloyl-poly-L-lysine (BPO-PLL), benzylpenicilloate, benzylpenicillin (PG), ampicillin (AMP), and AX. RAST for BPO-PLL and AX-PLL was done. When both skin test and RAST for BPO were negative, single-blind, placebo-controlled challenge tests were done to ensure tolerance of PG or sensitivity to AX. A total of 177 patients were diagnosed as allergic to beta-lactam antibiotics. We selected the 54 (30.5%) cases of immediate AX allergy with good tolerance of PG. Anaphylaxis was seen in 37 patients (69%), the other 17 (31%) having urticaria and/or angioedema. All the patients were skin test negative to BPO; 49 of 51 (96%) were also negative to MDM, and 44 of 46 (96%) to PG. Skin tests with AX were positive in 34 (63%) patients. RAST was positive for AX in 22 patients (41%) and to BPO in just 5 (9%). None of the sera with negative RAST for AX were positive to BPO. Challenge tests with AX were performed in 23 subjects (43%) to establish the diagnosis of immediate allergic reaction to AX, and in 15 cases (28%) both skin test and RAST for AX were negative. PG was well tolerated by all 54 patients. We describe the largest group of AX-allergic patients who have tolerated PG reported so far. Diagnosis of these patients can be achieved only if specific AX-related reagents are employed. Further studies are necessary to determine the exact extent of this problem and to improve the efficacy of diagnostic methods.

Determination of IgE antibodies to Polistes dominulus, Vespula germanica and Vespa crabro in sera of patients allergic to vespids.

The study was undertaken to investigate the presence of IgE antibodies to Polistes dominulus (PD), Vespula germanica (VG) and Vespa crabro (VC) in a large group of sera belonging to patients sensitized to Vespids in Spain. RAST values showed that although the majority of patients had IgE antibodies to PD, VG and VC, there was a marked predominance of PD. These results were related to the distribution of the insect in the areas where the sera were obtained. Due to geographical and insect distribution differences, the whole area was divided into three zones: Central, East and South. Comparison of the positive RAST values obtained indicated that, although the positivity to PD predominated over VG and this over VC, there were significant differences in percentage positivities to each vespid in the different regions studied. The results of the RAST absorption studies indicated that in most instances patients were originally sensitized to one vespid and were RAST positive to the other venoms due to cross-reactivity. Only in a minority of cases were coexisting antibodies to two insects present. These results show that PD and VG are the important vespids followed to a lesser extent by VC. This study provides relevant information concerning insect distribution sensitivity in a European country.

Tolerance to aztreonam in patients allergic to beta-lactam antibiotics.

To evaluate the safe use of aztreonam (AZT) in patients allergic to penicillins and other beta-lactam antibiotics we studied 29 patients from a group of subjects allergic to beta-lactams, diagnosed by presenting systemic reactions after skin tests or challenge tests. Skin tests with benzylpenicilloyl (BPO), benzylpenicilloate, benzylpenicillin, ampicillin, amoxicillin, cephamandole and AZT, radioallergosorbent test (RAST) to BPO and AZT, RAST inhibition and challenge tests were performed. One patient was skin test-positive to AZT, another patient was RAST AZT-positive. IgE antibodies were specific to AZT as demonstrated by RAST inhibition studies with AZT coupled to epsilon-amino caproic acid. Nevertheless, AZT was unable to inhibit either a pool of sera or individual sera positive to BPO. Although all our 29 patients tolerated the administration of AZT (including those with skin test or RAST positive) and AZT appears to be safe in these subjects, this does not indicate that all beta-lactam-allergic patients tolerate AZT administration.

Anaphylaxis to amoxycillin but good tolerance for benzyl penicillin. In vivo and in vitro studies of specific IgE antibodies.

Three patients are reported on who suffered anaphylactic reactions after amoxycillin (AX) treatment and challenge but tolerated benzylpenicillin (BP) parenterally and orally. Two of the three patients had positive skin tests and RAST to AX reagents but negative responses to benzyl penicilloyl (BPO) specific skin tests and RAST and the minor determinant mixture (MDM) skin test reagent. The third case was negative to all skin tests and RAST. RAST and RAST inhibition on the two positive sera suggest that the response is related to the acyl side chain of AX.

Allergic reactions to vespids: comparison of sensitivities to two species in a Mediterranean area.

We have studied a group of twenty-seven patients who suffer allergic reactions to vespids stings. Specific IgE antibodies to venom extracts from Polistes gallicus and Vespula germanica were measured by RAST, and the crossreactivity between the two venoms was compared using the RAST inhibition technique. We concluded that, in southern Spain, sensitization to P. gallicus was more prevalent than that to V. germanica, with 44% of the subjects in this study reacting to P. gallicus compared with 33% to V. germanica. However, there was a considerable degree of crossreactivity between the two species. It is evident that Polistes is an important species in this area; however, both in Spain and other Mediterranean countries, V. germanica venom is used almost exclusively for diagnosis and immunotherapy.

Studies of the specificities of IgE antibodies found in sera from subjects with allergic reactions to penicillins.

Penicillins are immunogenic when administered to humans and in some instances they can also be allergenic, inducing specific IgE antibodies. Whilst the major haptenic group, the penicilloyl, is well characterised, less is known about the relative importance of the different parts of the structure for antibody binding and how this can influence the specificity of patients response. In order to investigate this further, sera from subjects who had suffered an IgE-mediated reaction to penicillins were studied using the radioallergosorbent test (RAST) and RAST inhibition. The assays employed reagents related to the penicillins causing the reaction. Using 173 sera, positive RAST results were only found with reagents based on benzyl penicillin (BP) and amoxicillin (AX). Fifty-three positive sera were selected for further studies and categorized into three groups: (A) sera only RAST positive to AX, (B) sera only positive to BP and (C) sera positive to both penicillins. RAST inhibition studies were then carried out using monomeric penicilloyl conjugates and compounds representing parts of the penicilloyl structures of BP and AX. For all three groups, monomeric penicilloyl conjugates were the most efficient inhibitors but there were differences for the other compounds. Group A sera were also inhibited by the side chain amoxicillin, whereas group B sera were poorly inhibited by all other inhibitors. Group C sera showed two patterns of inhibition, both consistent with their more cross-reactive profile.

Specific IgE antibodies to vespids in the course of immunotherapy with Vespula germanica administered to patients sensitized to Polistes dominulus.

Sera from a group of 12 patients with anaphylactic reactions to vespids were studied. Field observations and RAST values suggested that the offending insect was Polistes dominulus (PD). Specific IgE antibodies to PD appeared in all cases and to Vespula germanica (VG) in nine. Absorption studies in these basal sera showed that IgE antibodies to VG were due to cross-reactivity with PD. The RAST value to both venoms was higher after immunotherapy (IT) in six cases. IgE antibodies increased to determinants common to both vespids, and in 41% of the cases to specific epitopes of VG venom allergens not initially detected in the basal sera. In one case antibodies increased only to VG without a corresponding rise to PD. These results indicate that if the correct venom to which the individuals are sensitized is not administered IgE antibodies may appear which were not initially detected in the patients' sera. The levels of these antibodies declined during the course of IT.

Nonimmediate reactions to betalactams: prevalence and role of the different penicillins.

In patients treated with penicillins, adverse cutaneous reactions can occur within minutes or may take several days to develop. IgE antibody-mediated reactions are well documented, but other mechanisms may also be involved. In particular, nonimmediate reactions have not been studied extensively, and the purpose of the present work was to establish the incidence of such reactions among a large group of patients and to study the penicillins involved. A total of 380 subjects with a history of a cutaneous reaction following administration of a penicillin antibiotic was included in the study. Skin tests and specific IgE measurements (RAST) were carried out using various penicillins and penicillin-related reagents, and patients were also challenged with various penicillins. In some patients with delayed skin test responses, skin biopsies were carried out. The tests confirmed that 74 subjects (19.4% of total investigated) had suffered a cutaneous reaction to a penicillin derivative, and 29 of these subjects (7.6% of total or 39% of confirmed) showed evidence of having suffered a nonimmediate reaction. The latter group were identified by giving a positive delayed direct challenge, and in 65% of the cases a delayed skin test response was detected. In most cases, these responses were to amino penicillins. Skin biopsies showed a lymphomonocytic cell infiltrate. Nonimmediate reactions to penicillins are a reproducible phenomenon, suggesting that a specific mechanism is responsible. By direct challenge, 93% of responders were positive to amino penicillins (10.3% ampicillin, 82.7% amoxicillin), indicating a major role for these penicillins in nonimmediate reactions.(ABSTRACT TRUNCATED AT 250 WORDS)