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Background Double-blind, placebo-controlled oral food challenges are the gold standard in food allergy diagnosis. Nevertheless, proper masking of peanuts is particularly complex owing to their intense flavor and odor. Thus, it is important to use validated recipes to ensure their adequate masking during oral food challenges. Objective To design and validate recipes containing masked peanuts for double-blind, placebo-controlled oral food challenges. Methods Two types of products (cookies and a custard‑type dessert) containing the masked peanuts and other ingredients with low allergenic potential were designed and validated. For this purpose, of the 24 initial cookie recipes and 12 initial custard recipes developed, those that did not exhibit significant differences in their texture were selected for sensory validation. Results Similarity triangle tests were performed using a panel of 36 selected tasters, enabling the validation of 1 pair of cookie recipes and 1 pair of custard-type dessert recipe, both with low allergenic potential and suitable for those with celiac disease and for vegans. Conclusion The validated recipes are of clinical and research interest because they allow to confirm a peanut allergy and detect a wide range of tolerated threshold doses, which makes it possible to provide specific indications for each patient.

In ihrem 2019 aktualisierten Bericht schreibt die Global Initiative for Asthma, die möglichen Vorteile der Allergen-Immuntherapie (AIT) gegenüber medikamentösen und Karenzmaßnahmen müssten gegen das Nebenwirkungsrisiko sowie den Aufwand und die Kosten dieser langfristigen Form der Asthmatherapie abgewogen werden. Mit dem Ziel, diesbezüglich bei einigen Aspekten des möglichen Einsatzes der AIT als Teil des therapeutischen Arsenals bei allergischem Asthma mehr Klarheit zu schaffen, hat ein allergologisches Expertengremium aus der Mitgliedschaft der spanischen Fachgesellschaft für Allergologie und klinische Immunologie (SEAIC), genauer gesagt aus deren Arbeitsgruppen für Immuntherapie und Asthma, eine Aufstellung häufiger Fragen für die klinische Praxis zusammengetragen. Dieses Dokument soll den aktuellen Stand wichtiger Aspekte der Anwendung der AIT bei Asthma darstellen, Ärztinnen und Ärzten als klinische Entscheidungshilfe dienen und zu besseren Behandlungsergebnissen für die Patienten beitragen.

Alternaria alternata is the most important allergenic fungus, with up to 20% of allergic patients affected. The sensitization profile of patients sensitized to A. alternata and how it changes when treated with immunotherapy is not known. Our objective is to determine the allergen recognition pattern of allergic patients to A. alternata and to study its association to the parameters studied in a clinical trial recently published. Sera of 64 patients from the clinical trial of immunotherapy with native major allergen Alt a 1 were analyzed by immunoblotting, 98. 4% of the patients recognized Alt a 1. The percentage of recognition for Alt a 3, Alt a 4, and/or Alt a 6, Alt a 7, Alt a 8, Alt a 10 and/or Alt a 15 was 1.6%, 21.9%, 12.5%, 12.5%, and 12.5% respectively. Of the 64 patients, 45 (70.3%) only recognized Alt a 1 among the allergens present in the A. alternata extract. Immunotherapy with Alt a 1 desensitizes treated patients, reducing their symptoms and medication consumption through the elimination of Alt a 1 sensitization, which is no longer present in the immunoblotting of some patients. There may be gender differences in the pattern of sensitization to A. alternata allergens, among others.

Al·lèrgia; Diagnòstic molecular; Recomanacions Alergia; Diagnóstico molecular; Recomendaciones Allergy; Molecular diagnosis; Recommendations The introduction of molecular diagnosis into routine clinical practice has substantially improved the diagnosis and management of allergic patients by allowing clinicians to precisely identify the allergenic molecule responsible for immunoglobulin E (IgE)-mediated allergies. However, it can be challenging to accurately interpret the results of molecular assays, partly due to the limited evidence base. In this context, a panel of experts with extensive experience in interpreting in vitro measures of total and serum specific IgE reviewed the available scientific evidence. After this review, the panel selected a series of representative case studies to demonstrate how determination of specific and total IgE values and the relationship between them (ratio analysis) can add value to the diagnostic process by more precisely defining the patient’s sensitization profile. Finally, the experts developed a series of recommendations on the clinical application of ratio analysis to optimize and complement the classical approach to allergy diagnosis.

There has been exciting progress in diagnosis and in the treatment of allergic patients. The objective of this review is to summarize the most relevant contributions in the past 10 years with a special focus on the pediatric population allergic to aeroallergens and provide the most relevant references and practical issues for the decision-making. Current guidelines on allergy diagnosis recommend a thorough clinical history as the first step, followed by allergen extract testing using an in vivo prick test and/or an in vitro specific IgE test. Molecular diagnosis is recommended when previous tests are inconclusive. In practice, the most important factors to decide the AIT treatment are the actual intensity and duration of the patient's symptoms and the availability of appropriate AIT products for the patient's sensitization profile at high allergen concentrations and with confirmed efficacy and safety from clinical trials. This document summarizes outstanding references for allergic immunotherapy decision-making and provides summary tables and figures analyzing the most important factors related to the decision for allergen immunotherapy and the safety risks related. The experts concluded that AIT is efficacious and safe for the treatment of allergic patients that is available for the most frequent aeroallergens.What is Known:• The prevalence of allergic asthma and rhinitis in children has increased in recent decades.• The efficacy and safety of allergen immunotherapy has been shown in multiple studies and systematic reviews.What is New:• This document summarizes outstanding references for allergic immunotherapy decision-making and provides summary tables and figures analyzing the most important factors related to the decision for allergen immunotherapy and the safety risks related. Recommendations of expert authors for the decision of the patients more suitable for allergen immunotherapy are included.

Background Oral immunotherapy is a frequent treatment for the management of food allergies, but adverse events (AE) are common. This study assessed the outcome of cow's milk oral immunotherapy (MOIT) in severe cow`s milk-allergic patients treated with omalizumab in a real-life setting. Methods OmaBASE was a national, multicenter, open, and observational registry that collected clinical, immunologic, and treatment from patients with food allergy receiving omalizumab. Results Data derived from 58 patients aged 10.3 years (IQR 6.3-13.2) and median milk-specific IgE 100 kU(A)/L at the start of omalizumab treatment. Most had experienced anaphylaxis by accidental exposures (70.7%) and had asthma (81.0%). Omalizumab in monotherapy induced tolerance to >= 6000 mg of cow's milk protein (CMP) to 34.8% of patients tested by oral food challenge. Omalizumab combined with MOIT conferred desensitization to >= 6000 mg of CMP to 83.0% of patients. Omalizumab withdrawal triggered more AE (P = .013) and anaphylaxis (P = .001) than no discontinuation. Anaphylaxis was observed in 36.4% of patients who discontinued omalizumab, and more in those with sudden (50.0%) rather than progressive (12.5%) discontinuation. At database closure, 40.5% of patients who had completed follow-up tolerated CMP without omalizumab (7.2% 1500-4500 mg; 33.3% >= 6000 mg). Conclusion Milk oral immunotherapy initiated under omalizumab allows the desensitization of subjects with severe cow's milk allergy even after omalizumab discontinuation. However, discontinuation of omalizumab can lead to severe AE and should be carefully monitored.

The Global Initiative for Asthma Report updated in 2019 stated that potential benefits of allergen immunotherapy (AIT), compared to pharmacological and avoidance options, must be weighed against the risk of adverse effects and the inconvenience and cost of the prolonged course of therapy in asthma. Thus, with the aim of clarifying some aspects with regard to the possible use of AIT in allergic asthma treatment armamentarium, a group of expert allergists from the Spanish Allergy and Clinical Immunology Scientific Society (SEAIC), particularly from the Immunotherapy and Asthma Interest Groups developed a frequently asked questions in clinical practice. This document updates relevant topics on the use of AIT in asthma and could facilitate physician clinical decisions and improve health outcomes for individual patients.

Omalizumab is a monoclonal antibody that binds and inhibits free serum immunoglobulin E, a mediator involved in the clinical manifestations of allergic asthma. Evidence for its efficacy and safety in the treatment of moderate-to-severe allergic asthma is based primarily on studies in adolescents and adults. However, there is increasing evidence of its utility in children with allergic asthma aged 6-12 years. Areas covered: This article reviews efficacy, safety, and effectiveness of omalizumab in the treatment of moderate-to-severe allergic asthma in children aged 6-12 years in clinical trials and in studies in clinical practice. Pharmacoeconomic aspects of its use among this population and the positioning of omalizumab in pediatric asthma management guidelines are also discussed. Additionally, an algorithm for the management of poorly controlled severe pediatric asthma in children older than 6 years is proposed. Electronic databases, such as PubMed, were searched for terms Asthma and Omalizumab and for asthma management guidelines. Expert commentary: Add-on omalizumab is an effective maintenance therapy in children aged 6-12 years with poorly controlled moderate-to-severe allergic asthma treated with medium-high inhaled corticosteroids doses and inhaled long-acting β2-agonists. Omalizumab appears safe in children in both clinical trials and real-life setting and may be cost-effective.

Allergic respiratory diseases are major health problems in paediatric population due their high level of prevalence and chronicity, and to their relevance in the costs and quality of life. One of the most important risk factors for the development of airway diseases in children and adolescents is atopy. The mainstays for the treatment of these diseases are avoiding allergens, controlling symptoms, and preventing them through sustained desensitization by allergen immunotherapy (AIT). AIT is a treatment option that consists in the administration of increasing amounts of allergens to modify the biological response to them, inducing long-term tolerance even after treatment has ended. This treatment approach has shown to decrease symptoms and improve quality of life, becoming cost effective for a large number of patients. In addition, it is considered the only treatment that can influence the natural course of the disease by targeting the cause of the allergic inflammatory response. The aim of this publication is to reflect the advances of AIT in the diagnosis and treatment of allergic respiratory diseases in children and adolescents reviewing articles published since 2000, establishing evidence categories to support the strength of the recommendations based on evidence. The first part of the article covers the prerequisite issues to understand how AIT is effective, such as the correct etiologic and clinical diagnosis of allergic respiratory diseases. Following this, the article outlines the advancements in understanding the mechanisms by which AIT achieve immune tolerance to allergens. Administration routes, treatment regimens, dose and duration, efficacy, safety, and factors associated with adherence are also reviewed. Finally, the article reviews future advances in the research of AIT.

Background: There have been few studies conducted on the efficacy and safety of specific immunotherapy with allergen extracts of fungi compared with other allergen extracts, and there are no data on the major allergen Alt a 1 of the fungus Alternaria alternata. Objectives: We sought to evaluate the efficacy and safety of subcutaneous immunotherapy with 2 different doses of Alt a 1 in patients with rhinoconjunctivitis caused by sensitization to A alternata. Method: We performed a multicenter, randomized, double-blind, placebo-controlled trial with Alt a 1 administered subcutaneously in patients with allergic rhinoconjunctivitis with or without controlled asthma aged 12 to 65 years. Three groups were included: the placebo group and active groups receiving 0.2 or 0.37 mu g of Alt a 1 per dose. The main end point was the combined symptom and medication score. Secondary end points were cutaneous reactivity and serum IgE and IgG(4) levels to Alt a 1. Recorded adverse reactions were graded according to World Allergy Organization criteria. Results: There were significant reductions in the combined symptom and medication score for the 0.37-mu g dose of Alt a 1 compared with placebo at 12 months of treatment. Reduced cutaneous reactivity and IgE levels, together with increased IgG(4) levels, were demonstrated for the 2 active groups versus the placebo group. A similar safety profile was found for both active groups compared with the placebo group. No serious adverse drug reactions were reported. Conclusion: Immunotherapy with Alt a 1 was efficacious and safe, reducing the symptoms and medication consumption associated with rhinoconjunctivitis after only 1 year of treatment. The clinical benefits were associated with reduced skin reactivity and specific IgE levels and increased IgG(4) levels.

Background: Allergen immunotherapy clinics (AITCs) in Spain differ widely in terms of structure, organization, resources, and portfolio of services. Therefore, it is essential to unify treatment criteria and define quality standards for the most complex AITCs. Objective: To establish a series of recommendations that make it possible to guarantee quality and safety in the administration of immunotherapy and define quality standards for the most complex AITCs. Methods: This project began with an online survey of 65 allergy departments/units throughout Spain in 2013. Next, a 2-phase consensus process was carried out. In the first phase, 10 experts defined and agreed on the standards using the RAND/UCLA Appropriateness method; in the second, the agreements were validated by means of a 2-round Delphi consultation with 84 experts. Results: Consensus was reached on minimum safety and quality criteria in the administration of allergen immunotherapy, and 2 levels of highly complex AITCs were defined: accredited AITCs and accredited AITCs with excellence. Consensus was also reached on quality standards and accreditation criteria for both levels. Conclusions: This project is pioneering in terms of its purpose (the definition of quality standards for AITCs) and of the use of structured participation techniques (combination of the RAND/UCLA and Delphi methods). It enabled the design of minimum standards for quality and safety in administering AIT, as well as quality criteria for accreditation of AITCs supported by a broad panel of experts from the Spanish Society of Allergology and Clinical Immunology.

Asthma is frequently associated with atopy, characterized by the production of specific immunoglobulin E in response to environmental allergens. Currently, two types of allergen immunotherapy (AIT) are used in clinical practice: subcutaneous and sublingual immunotherapy, both accepted as key components of the therapeutic repertoire for allergic rhinitis and conjunctivitis. However, their role in asthma remains controversial. The present document is aimed at providing the clinicians with a review of the evidence on the use of AIT in asthma, focusing on the most relevant aspects of its mechanism of action, its efficacy, and existing data on safety, tolerability, and cost-effectivity, both in pediatric and adult populations. A systematic search of MEDLINE, Cochrane, and Clinical Trials databases from 2000 to April of 2016 was carried out by a panel of experts from the Spanish Allergy and Clinical Immunology Scientific Society. Relevant studies prior to the year 2000 included in ulterior systematic reviews were also considered. More than 4000 articles were identified during the search and 241 were selected to retrieve available evidence on AIT, which was graded according to the Oxford classification. All the group members reviewed the resulting text until the final version reached the consensual agreement. A summary of recommendations on the more relevant topics are proposed. The role of AIT as a valuable therapeutic strategy for prevention of exacerbation and progressive decline in lung function is highlighted. Future research should include specific tools for asthma evaluation when assessing AIT effectiveness in asthmatic patients.

International audience; BACKGROUND:Safety data on 'real-life' allergen immunotherapy (AIT) in children and adolescents is usually extrapolated from studies in adults.METHODS:Patients aged 18 or under initiating aeroallergen AIT were evaluated in a prospective European survey. Patient profiles and systemic reactions (SRs) were recorded. Descriptive, univariate and multivariate analyses were used to identify risk factors for SRs.RESULTS:A total of 1563 patients (mean ± SD age: 11.7 ± 3.9 years; rhinitis: 93.7%; asthma: 61.5%; polysensitization: 62.5%) and 1578 courses of AIT were assessed. Single-allergen AIT was administered in 89.5% of cases (n = 1412; mites: 49%; grass pollen: 25.8%; tree pollen: 8.7%; Alternaria: 4.6%; dander: 0.8%; weed pollen: 0.6%). Subcutaneous AIT (SCIT) was used in 71.4% (n = 1127) of the treatments, including 574 (50.9%) with natural extracts. Sublingual AIT (SLIT) was used for the remaining 451 treatments (drops: 73.8%; tablets: 26.2%). The mean ± SD follow-up period was 12.9 ± 3.3 months. The estimated total number of doses was 19,669 for SCIT and 131,550 for SLIT. Twenty-four patients (1.53%) experienced 29 SRs. Respiratory (55.7%) and skin symptoms (37.9%) were most frequent. Anaphylaxis was diagnosed in 3 SRs (10.3%), and adrenaline was administered in 2 of these cases. In a univariate analysis, the risk of SRs was lower in mite-sensitized patients and higher in cases of pollen polysensitization (>3), grass pollen extracts and the use of natural extracts (vs. allergoids).CONCLUSIONS:In a real-life paediatric setting, AIT is safe. SRs are infrequent and generally not severe. Pollen polysensitization, grass pollen extracts and natural extracts (vs. allergoids) were risk factors for AIT-associated SRs.

Allergy Immunotherapy is the only treatment able to modify the natural history of the respiratory allergic disease. It is indicated in IgE-mediated rhinoconjunctivitis and/or allergic asthma in both children and adults whenever more than occasional use of anti-inflammatory or controller medications is needed. Only well-standardized products should be used after precise diagnosis has been achieved. Efficacy of allergen immunotherapy (AIT) with mite and pollen extracts persist once treatment is discontinued, and for that AIT may be considered the only treatment able to change the natural history of the allergic disease.

Allergic diseases often occur early in life and persist throughout life. This life-course perspective should be considered in allergen immunotherapy. In particular it is essential to understand whether this al treatment may be used in old age adults. The current paper was developed by a working group of AIRWAYS integrated care pathways for airways diseases, the model of chronic respiratory diseases of the European Innovation Partnership on active and healthy ageing (DG CONNECT and DG Santé). It considered (1) the political background, (2) the rationale for allergen immunotherapy across the life cycle, (3) the unmet needs for the treatment, in particular in preschool children and old age adults, (4) the strategic framework and the practical approach to synergize current initiatives in allergen immunotherapy, its mechanisms and the concept of active and healthy ageing. ispartof: Clinical and Translational Allergy vol:6 issue:1 pages:41-47 ispartof: location:England status: published

Background Component-resolved diagnostics (CRD) has recently been introduced into clinical allergology. Objective The aim of this study was to assess the contribution that this new diagnostic technique makes to conventional diagnosis in patients with pollen allergy, comparing CRD with conventional technologies, and to compare 2 CRD methods, Advia-Centaur and Microarray-ISAC. Methods Serum samples from 120 pollen-allergic patients were obtained. Immunoglobulin (Ig) E to total extracts (CAP System) and individual allergens using both CRD methods were determined. Results The 3 diagnostic methods were in agreement in 62.5% of cases. In 30%, the CRD modified the conventional diagnosis either by detecting new relevant sensitizations (mainly to Olea ) or by ruling out clinically irrelevant sensitizations caused by panallergens. The main differences between the 2 CRD methods were the deficiency in the ISAC version we used (ISAC-CRD-89) to detect sensitizations to Salsola and Plantago and that Advia-Centaur did not detect sensitizations to cypress. For all allergens except for Par j 1, a significant association in the frequency of sensitization was seen with the 2 CRD techniques and good agreement when comparing the results of the 2 methods in all cases. Significant correlation was found in the concentration of specific IgE in the 2 techniques for the most prevalent allergens in our setting. The results of the different profilins analyzed using Microarray-ISAC were superimposable although somewhat lower in the case of Phl p 12. Conclusions Component-resolved diagnostics modified the conventional diagnosis in 30% of cases. The results from the 2 CRD methods showed good agreement and correlation for most allergens.

Background: Once the optimal dose is reached, subcutaneous immunotherapy [SCIT] with mite extract is capable of reducing symptoms and the need for rescue medication. Objective: To assess the capacity of a subcutaneous extract of mites [D. pteronyssinus] to bring about a reduction in concomitant medication as well as in vivo and in vitro changes in just 2-3 months of treatment in patients with allergic asthma. Methods: A total of 45 patients with persistent mildmoderate allergic asthma due to sensitisation to D. pteronyssinus were included in a multi-centre, double-blind, placebocontrolled trial. Length of treatment was 4 months. After a period for adjusting medication in order to classify asthma severity appropriately, patients were commenced on treatment of 400 or 800 μg/day of budesonide as concomitant medication. Results: After 4 months of treatment there were no significant changes in the budesonide dose between the active group and the placebo group. In the active group there was a significant difference between active and placebo group in sIgG4 [p=.0003], as well as a significant increase in the cutaneous tolerance index [2.81, CI 95%: 1.29 – 7.48, which was significant with a Confidence Interval of 95%]. These changes were not observed in the placebo group. Conclusion: After just 4 months of treatment, SCIT was capable of inducing in vivo and in vitro changes, but these changes were not reflected in improved clinical outcome within the first 4 months of therapy.

Background: Peach allergy is highly prevalent in the Mediterranean area; it is persistent and potentially severe, and therefore a prime target for immunotherapy. We aimed to study the efficacy and safety of sublingual immunotherapy (SLIT) with a peach extract quantified in mass units for Pru p 3, the peach lipid transfer protein. Methods: Randomized, double-blind, placebo-controlled (DBPC) clinical trial. The main efficacy outcome was the change in the response to a DBPC food challenge (DBPCFC) with peach. Secondary efficacy outcomes were the changes in skin prick test (SPT), and in specific immunoglobulin E (IgE) and IgG4 to Pru p 3. Tolerance was assessed with a careful recording of adverse events. Results: After 6 months of SLIT, the active group tolerated a significantly higher amount of peach (three- to ninefold), presented a significant decrease (5.3 times) in SPT, and a significant increase in IgE and IgG4 to Pru p 3. No significant changes were observed within the placebo group. Statistically significant inter-group differences were only observed in the SPT and IgG4 responses. No serious adverse events were reported. Systemic reactions were mild, and observed with a similar frequency in both groups. Local reactions were significantly more frequent in the active group (three times) and 95% of them restricted to the oral cavity. Conclusion: In this first exploratory clinical trial, SLIT for peach allergy seems to be a promising therapeutic option that could modify the clinical reactivity of the patients to peach intake and the underlying immunological response with a good tolerance.

Background: The optimal dose of five-grass pollen sublingual tablet immunotherapy (SLIT) was established recently by the primary criteria Rhinoconjunctivitis Total Symptom Score (RTSS) from the first treatment season. Secondary and exploratory criteria, such as RTSS at peak pollen season, exploratory combined symptom and rescue medication use score, quality of life and immunological markers are calculated and described in this analysis. Methods: Six hundred and twenty-eight patients with grass pollen rhinoconjunctivitis (≥2 years duration) were randomized in a double-blind, placebo-controlled trial conducted in Europe. Patients received once-daily SLIT (Stallergenes, Antony, France) of 100IR, 300IR, 500IR or placebo, starting 4 months before grass pollen season and throughout the 2005 season. Patients were instructed to take rescue medication only if symptoms were severe and record symptom severity on using the RTSS. Results: Both 300IR and 500IR doses significantly reduced mean RTSS at pollen peak (P = 0.0005 and P = 0.0014, respectively) and the exploratory combined score (P = 0.0001 and P = 0.0026, respectively) compared with placebo. Compared with patients in the placebo group, those who were taking the 300IR and 500IR doses reported significantly improved quality of life using the mean Rhinoconjunctivitis Quality of Life Questionnaire scores during the peak of the pollen season (P

Methods Retrospective review of patients attending the Emergency Department (2009-2013) for a NSAID induced anaphylaxis and with a tryptase determination. Patients were split into 3 groups according to the allergy workup Results Selective reactions (S) were defined by positive skin results and/or negative challenges with other NSAID; non-selective (NS) reactions were defined by the existence of symptoms with several NSAID or after positive challenge results. Those cases who did not comply with the previous conditions were non-conclusive (NC). We analysed: demographics, severity of the episode (Chi Square test), and rate of tryptase higher than 11.4 mcg/l (Chi Square test), median tryptase values and timing of sample obtention (Kruskall-Wallis).

There are no documented studies that describe natural rubber latex (NRL) sensitization in children with a history of surgical intervention but without any congenital malformation (urogenital anomalies, spina bifida, etc.), although some authors have studied NRL allergy in children without a history of surgical intervention. The aim of this work was to evaluate the sensitization profile to single NRL allergens in children without spina bifida and without repeated surgical interventions, by using different recombinant and natural latex allergens in two analytical techniques: specific serum immunoglobulin E (IgE) quantification and flow cytometry determination of activated basophils expressing CD63, after stimulating cells from patients with NRL allergens. A total of 23 patients and 10 healthy children were selected. Conjunctival and in-use NRL provocation tests were carried out, as well as specific IgE determination in all patients' and controls' sera with the recombinant NRL allergens: rHev b 1, rHev b 2, rHev b 3, rHev b 5, rHev b 6.01, rHev b 6.02, rHev b 8, rHev b 9 and rHev b 11 and with NRL (k82) using appropriate ImmunoCAPs. The Basophil Activation Test (BAT) was performed with whole latex extract and with the recombinant allergens rHev b 5 and rHev b 6.01, as well as with the natural allergen Hev b 6.02. The sensitivity and the specificity of NRL-specific IgE (k82) were 100%. Positive IgE responses to rHev b 5 were found in sera of 10 children, to rHev b 6.01 in 16 and for rHev b 6.02 in 15 children's sera. Specific IgE to rHev b 8 was found in four sera of the children. We only found significant differences in sensitization to rHev b 5 in children with two or more surgical interventions compared with the non-intervened group or those with only one intervention. Specific IgE in sera of children with latex-fruit syndrome recognized rHev b 6.02, but not to rHev b 11. The patients sensitized to Hev b 8, Hev b 9 and/or Hev b 11 were atopic. The four patients presenting a positive response to the NRL profilin Hev b 8 were allergic to pollen. The BAT against whole NRL extract was positive in 22 of 23 children; against rHev b 5 in 14 of the patients studied; against rHev b 6.01 in seven cases and against nHev b 6.02 in 19 children. In all the control subjects, the results using this technique were negative. If combined rHev b 5, rHev b 6.01 and nHev b 6.02 together, BAT could detect 20 of the 23 children with latex allergy. The combined use of ImmunoCAP with all the recombinant NRL allergens and BAT with rHev b 5, rHev b 6.01 and nHev b 6.02, enabled the identification of NRL allergy in 22 of 23 patients. There is a positive and significant correlation between sensitization to Hev b 5 and the number of interventions. BAT and allergen-specific IgE determination could be used as first-line in vitro diagnostic tests in patients with NRL allergy.

Background The conventional schedule for subcutaneous immunotherapy with allergen extracts, although efficacious and safe, is slow during the dose-increase phase. Objective We sought to compare the efficacy and safety of subcutaneous immunotherapy with Dermatophagoides pteronyssinus standardized extract given in a 6-week cluster period and a conventional 12-week schedule during the incremental-dose phase. Methods Of 239 patients with rhinitis, allergic bronchial asthma, or both caused by D pteronyssinus , 120 were randomly assigned to the cluster schedule, and 119 were randomly assigned to the conventional schedule. A biologically standardized D pteronyssinus depot extract (ALK-Abello S.A., Madrid, Spain) was administered in a placebo-controlled, double-blind fashion during the initial phase of cluster or conventional treatment. We recorded adverse reactions, clinical efficacy, cutaneous reactivity, and serum specific immunoglobulins to D pteronyssinus before immunotherapy, when the maximum dose was reached in the cluster and conventional schedules, and after 1 year of treatment. Results The cluster schedule reduced the time to maintenance dose by 46% and caused systemic adverse reactions (all mild) after only 0.15% of injections, with no differences in comparison with the conventional schedule. Cluster immunotherapy led to decreases in asthma and rhinitis symptoms, reduced the cutaneous reactivity, and produced the increase in specific IgE and IgG 4 levels on reaching the maintenance dose in the sixth week, 6 weeks earlier than with the conventional schedule. Conclusion The cluster schedule for the initial phase of immunotherapy with incremental doses of D pteronyssinus is a safe alternative to conventional immunotherapy and offers the further advantage of achieving clinical and immunologic improvements sooner.

Summary Background Several lipid-transfer proteins (LTPs) have been identified as important food allergens, especially in fruits of the Rosaceae family. The major peach (Prunus persica) allergen has been identified, sequenced and designated Pru p 3. Objective To present Pru p 3 as an aeroallergen able to induce occupational asthma. Methods A thorough investigation was performed in a fruit grower with occupational asthma. Skin prick–prick tests with peach leaves and prick tests with perennial respiratory allergens and pollens, fruits and peach leaf extracts were done. Serum-specific IgE was tested for peach leaf, peach fruit, peach skin and respiratory allergens that were positive in skin prick tests. Specific bronchial provocation tests (BPTs) with extracts of peach leaf were also done. Before and 24 h after the BPT, BPTs with methacholine and sputum induction were done. The IgE reactivity pattern to peach leaf and fruit extracts and to Pru p 3 was identified by using SDS-PAGE and immunoblotting. Blotting inhibition of peach leaf extract by Pru p 3 was also performed. The putative allergen was quantified in leaf and fruit skin extracts with ELISA based on an anti-Pru p 3 antibody. Results Skin tests were positive for peach leaf and fruit. The BPT was positive, with immediate and delayed response. This test induced a decrease in PD20 (dose of agonist that induces a 20% fall in FEV1) methacholine and an increase in eosinophils and eosinophil cationic protein in sputum. Peach leaf extract contained concentrations of Pru p 3 similar to those found in peach skin. Specific IgE immunodetection showed that patient's sera reacted with Pru p 3, and with a single major band from the peach leaf extract fully inhibited by Pru p 3. Conclusion Pru p 3 from peach leaves can act as a respiratory allergen and cause occupational rhinoconjunctivitis and asthma.

Summary Background Allergen vaccination is effective in mite-allergic asthma. Liposomes are immunological adjuvants that can act as allergen carriers. Objective To evaluate the immunological and functional effects of a liposome-entrapped D. pteronyssinus vaccine on mite monosensitive, mild asthma patients. Methods A double-blind, placebo-controlled trial was conducted on 26 asthma patients who randomly received vaccination or placebo for 1 year. The levels of exposure to Der p 1 allergen were constant during the study. Allergen bronchial challenge was made at the beginning (T0) and after 1 year of treatment (T12). The day before and 24 h after the allergen provocation, patients were challenged with methacholine (Mth) (until FEV1 fell by 40%) and blood and sputum samples were obtained. Dose–response curves to Mth were evaluated in terms of Mth-PD20 (dose of Mth that induced 20% drop in FEV1), slope (Mth-DRS) and level of plateau. Blood and sputum eosinophils and serum levels of eosinophil cationic protein (ECP) and intercellular adhesion molecule-1 (ICAM-1) were measured. Results Groups were comparable at the start of the trial. At T12, previous to the allergen challenge, the active group showed higher values of both FEV1 and Mth-PD20 and lower values of Mth-DRS. The number of patients presenting a level of plateau increased in the active group (from two to four) and decreased in the placebo group (from two to one). At T12, before the allergen challenge, serum ECP levels increased in the placebo group and blood eosinophils showed a trend towards lower numbers in the active one. The immediate response and the changes in Mth-DRS values, sputum eosinophils and serum ECP levels following the allergen challenge were attenuated in the active group. Conclusion Liposome-entrapped D. Pteronyssinus vaccination: (i) protects mild asthma patients from the worsening of asthma due to sustained mite exposure; and (ii) reduces the functional and inflammatory changes induced by allergen bronchial provocation.

Latex allergy currently constitutes a serious problem because of the severity of its symptoms and the at-risk groups it affects. Since complete avoidance of this substance is practically impossible, in the last few years intense efforts have been made to standardize a latex extract with the aim not only of improving clinical diagnosis but also of being able to offer other therapeutic alternatives, such as specific immunotherapy.Since 1998, reports of immunotherapy with oral (three patients) subcutaneous (one patient) and sublingual latex desensitization (one patient) have been published. In all cases, clinical improvement was evident. In 2000, Laynadier published the first pilot study, a phase IIB multicenter, randomized, double-blind, placebo-controlled trial that evaluated the efficacy and safety of specific immunotherapy with latex in patients with occupational allergy. Twenty health care workers without obvious latex exposure and with latex allergy-induced symptoms of rhinitis and/or asthma were included. Treatment started with a 2-day course of rush immunotherapy in hospital and maintenance therapy was continued for 1 year. Efficacy was assessed by symptom and medication scores and by variation in the conjunctival reactivity threshold. The safety of the extract was also evaluated. In the overall analysis of symptom score, the treated group showed a marked improvement and the medication score was significantly lower in patients in the active treatment group than in the placebo group. Concerning safety, almost half the patients receiving active treatment showed local reactions starting with the first injection and four of the nine patients in this group suffered moderate-to-severe systemic reactions. In view of this first clinical trial, it can be concluded that this treatment is effective but that its tolerance is low.A second clinical trial with the same characteristics and extract is currently underway. Its aim is to validate the previous protocol, confirm the efficacy of specific immunotherapy with latex, improve its safety and, if possible, determine the optimal dose.J. Sastre et al. have recently (Formigal 2002) presented the results of the first double-blind study with latex immunotherapy using an extract standardized by the ALK-Abello-Espana group. The authors included 24 patients with latex sensitization and symptoms of occupational allergy. To diagnose respiratory allergy, an inhalation challenge was performed in a closed 7-m2 chamber and, in case of contact urticaria, glove-wearing and rubbing tests were performed, using a vinyl glove as negative control. Treatment consisted of a first phase of incremental doses for 14 weeks, with 18 injections, followed by maintenance doses for 6 months. Sixteen patients received active treatment and 8 received placebo. Of the 578 doses administered, adverse effects were observed in 41 (7.1 %). There were 21 immediate systemic reactions (5.7 % of the doses) and 10 delayed systemic reactions (2.6 % of the doses). Adverse effects were more frequent in patients with underlying respiratory disease (p < 0.05). After 6 months' treatment, a clear improvement in the cutaneous response index was found in the active treatment group and in the rubbing and glove-wearing tests. The authors conclude that the immunotherapy tested was a high-risk treatment and that the greatest clinical improvement was found in cutaneous symptoms.In conclusion, although effective, latex immunotherapy is currently a high-risk treatment.

Background Subcutaneous immunotherapy (SCIT) discontinuation data in children remain scarce. Objective We sought for differences in the clinical efficacy of 3 vs. 5 yr of SCIT in children with dust mite respiratory allergy. Methods We performed a 5-yr, phase IV prospective study. After the first year, the patients were randomized to 3 (IT3) or 5 yr of treatment (IT5). Efficacy was assessed at 3rd and 5th year by symptom and medication scores and visual analog scales (VAS). Skin tests with common allergens and in vitro assessments were also performed. Results Eighty-one children (mean age: 9 yr) were randomly assigned to 3 (IT3: 41) or 5 yr (IT5: 40) of immunotherapy. After 3 years, rhinitis global scores decreased in IT3 (44%; p = 0.002) and in IT5 (50%; p = 0.001). Asthma global, symptom and medication scores decreased by 100% in IT3 (p = 0.001) and IT5 (p = 0.001). VAS scores also diminished significantly (IT3: 70%, p = 0.001; IT5: 62.5%; p = 0.001). At 5th year, global rhinitis scores were reduced an additional 30% in IT5 children. Comparisons between both groups did not show differences in rhinitis (p = 0.055), asthma global scores (p = 0.948) or VAS scores at 5th year. Twenty percent of IT5 (p = 0.002) and 7% of IT3 children (p = 0.705) developed new sensitizations. At 5th year, sIgG4 determinations decreased in IT3 without significant variations in IT5. Conclusions Three years of SCIT induced significant improvement in children with dust mite respiratory allergy, but a 5-yr course added clinical improvement in rhinitis.

Study objective: To examine the baseline factorsinfluencing the occurrence and magnitude of immediate- and late-phaseresponses in asthmatic patients after an allergen-induced bronchialprovocation test (A-BPT). Design: Cross-sectionalanalysis in a homogenous group of 31 mild, Dermatophagoidespteronyssinus -allergic patients with asthma. Setting: Allergy Department, Hospital Virgen del Camino, Pamplona, Spain. Interventions and measurements: Patients completed an asthma symptom questionnaire and underwent skintests, sputum induction, and methacholine bronchial provocation test. The A-BPT was performed on a separate day. Sputum cell profile andeosinophil cationic protein (ECP), tryptase, albumin, and interleukin-5levels were quantified in the entire sputum supernatant. Assayswere done for eosinophils in blood, and/or ECP, and total and specific, IgE levels in serum. Exposure to D pteronyssinus majorallergens (Der p1 and Der 2) was measured by an assay based onmonoclonal antibodies. Results: A-BPT findings werepositive in all patients, and late-phase responses were detected in29%. Late responders were exposed to higher levels of Der p1(p = 0.028), had greater levels of ECP (p = 0.007) and albumin(p = 0.019) in sputum, and showed a trend toward higher lymphocytenumbers (p = 0.053) in sputum than isolated early responders. Theallergen-induced provocative dose that induced a fall in, FEV 1 values ≥ 20% from the postdiluent values correlatedwith bronchial hyperresponsiveness ( r = 0.36). Thelate-phase response magnitude correlated with Der p1 exposure( r = 0.49) and showed a trend toward correlation withsputum ECP levels ( r = 0.38). Conclusion: Factors involved in the development ofallergen-induced immediate- and late-phase responses are different. Allergen natural exposure might prime the infiltration of the airway byactivated inflammatory cells enhancing the appearance and the severityof late-phase responses.

Bronchial eosinophilic inflammation and bronchial hyperresponsiveness (BHR) are the main features of allergic asthma (AA), but they have also been demonstrated in allergic rhinitis (AR), suggesting a continuity between both diseases. In spite of not fully reproducing natural allergenic exposure, the allergen bronchial provocation test (A-BPT) has provided important knowledge of the pathophysiology of AA. Our aim was to verify the existence of a behavior of AA and AR airways different from the allergen bronchial challenge-induced airway eosinophilic inflammation and BHR changes. We studied a group of 31 mild and short-evolution AA and 15 AR patients, sensitized to Dermatophagoides pteronyssinus. The A-BPT was performed with a partially biologically standardized D. pteronyssinus extract, and known quantities of Der p 1 were inhaled. Peripheral blood (eosinophils and ECP) and induced sputum (percentage cell counts, ECP, albumin, tryptase, and interleukin [IL]-5) were analyzed, before and 24 h after A-BPT. Methacholine BHR, assessed before and 32 h after the A-BPT, was defined by M-PD20 values and, when possible, by maximal response plateau (MRP). The A-BPT was well tolerated by all the patients. AA presented a lower Der p 1 PD20 and a higher occurrence of late-phase responses (LPR). M-PD20 values decreased in AA, but not in AR, patients. MRP values increased in both groups. Eosinophils numbers and ECP levels increased in blood and sputum from both AA and AR, but only the absolute increment of sputum ECP levels was higher in AA than AR patients (P=0.025). The A-BPT induced no change in sputum albumin, tryptase, or IL-5 values. We conclude as follows: In spite of presenting a lower degree of bronchial sensitivity to allergen, AR patients responded to allergen inhalation with an eosinophilic inflammation enhancement very similar to that observed among AA. MRP levels increased in both AA and AR patients after allergen challenge; however, M-PD20 values significantly changed only in the AA group, suggesting that the components of the airway response to methacholine were controlled by different mechanisms. It is possible that the differences between AR and AA lie only in the quantitative bronchial response to allergen inhalation.

Background: Anisakis simplex is a parasite of fish, and in the case of human infestation, it should be considered as a possible cause of gastrointestinal disease, especially in countries where raw or undercooked fish is a frequent food. Clinical features of anisakiasis may simulate acute abdominal pain, such as that found in patients with gastric ulcers, appendicitis, and Crohn's disease. Furthermore, many cases of anisakiasis are diagnosed as eosinophilic gastroenteritis, which is a broad term for a specific disease. Objective: The purpose of this study was to investigate the immunopathogenesis of human gastrointestinal infestation by A simplex . Methods: Thirteen intestinal biopsy specimens from patients with anisakiasis were analyzed for the presence of messenger (m)RNA for different cytokines and inflammatory mediators by RT-PCR. Specific IgE, eosinophil cationic protein, eosinophil protein X, and tryptase levels were measured in each patient s serum. Also, cell cultures were set up with lymphocytes from some patients and stimulated in vitro with Anisakis and Ascaris antigens. Results: We performed immunologic phenotyping in 13 patients. All patients underwent biopsy after emergency surgery caused by episodes of acute abdominal pain. In all cases inflammatory infiltrate composed of eosinophils and lymphocytes was found in the intestinal wall. We demonstrated that after infestation, a T H2 -type immune response occurred. Also, major basic protein, nitric oxide, and eotaxin were found in the tissue, and eosinophil cationic protein and eosinophil protein X levels were elevated in sera. Conclusion: These data and in vitro lymphocyte cultures indicate that a T H2 mechanism plays an important role in the inflammatory infiltrate produced by the anchorage of parasites in the gastrointestinal wall. (J Allergy Clin Immunol 1999;104:637-43.)

Summary Background Occupatiotial asthma among cereal workers is frequently due to cereals but other allergens can also be responsible. Objective We evaluated the allergens causing occupational asthma in the patients who had been diagnosed in our Department during the last 5 years. Specific bronchial reactivity to the implicated allergens was assessed and compared by standardized bronchial challenge. Methods Twenty-one patients (12 bakers, three millers and six farmers) were studied. We carried out in vivo tests (skin and challenge tests) and in vitro tests (specific IgE measurement) with cereals, enzymes, soyabean, storage mites and egg. A definitive diagnosis was established by means of specific bronchial provocation tests (BPT), except in three patients in whom it could not be carried out due to the severity of their asthma. In these cases the causative agent had to be determined by means of conjunctival challenge. Results Cereals were the main sensitizers among bakers (75%) and farmers (66%). Bakers were also sensitive to a-amylase (41%) and soyabean (25%), and farmers, to soyabean (33%) and storage mites (33%). Occupational asthma was due to cereals, soyabean and storage mites among millers. Conclusions Besides cereals, other allergens such as enzymes, leguminous, egg and storage mites can be the causative agents of occupational asthma among cereal workers. Sensitization to different allergens in the different jobs is very likely due to differences in exposure.

Immunotherapy selectively modulates the allergen-specific immune response. It involves the gradual administration of increasing amounts of allergen for the purpose of inducing protective immunological changes and it is the only curative approach for specific type I allergy.Description of the allergic inflammation.- Comprehension of the early cellular changes after specific immunotherapy has been initiated. Exposure of the mechanisms involved in tolerance induction by regulatory T cells (Treg) with the inhibition of the Th2 responses. Comprehension of IL-10 and transforming growth factor (TGF- ) roles. Explanation of specific IgE, IgG and IgA changes. Description of the suppression of inflammatory responses during immunotherapy.

Summary Background There are few studies comparing the sensitization with mite allergens from different mite species which could potentially be the cause of allergy. Objective To improve the diagnosis of mite allergic patients from a diverse territory in which D. pteronyssinus/D. farinae mites together with storage mites could be present in the environment. Methods Four hundred and seventy-seven patients (both children and adults) from different regions, covering the main mite prevalent areas of Spain, were recruited. sIgE to eight allergens was measured together with SPT to whole mite extracts, level of mite allergen exposure, and specific IgG4. BAT and CAST was performed in a subgroup of patients. Results D. pteronyssinus and L. destructor were more prevalent in Atlantic areas, whereas D. farinae predominate in Mediterranean areas. About 90% of patients were sensitized to group 1 and/or group 2 allergens. Group 2 was the most prevalent, and the IgE response/ intensity of sensitization in BAT was higher. sIgE to Der p 2/Der f 2 was almost fully cross-reactive, but no cross-reactivity was detected with Lep d 2. Group 1 allergens were also cross-reactive, but in some patients a species-specific response was observed. sIgE to Lep d 2 was associated with SPT results to storage mites. Sensitization to Der p 1 was more frequent in children, whereas Lep d 2 sensitization was more frequent in adults. A higher ratio IgE/IgG4 to Der p 2 was associated with the presence of allergic asthma. Conclusion An improved diagnosis algorithm has been established. Group 2 allergens seem to have a leading role in mite allergy, but as group 1 sensitization could be speciesspecific in some patients and its prevalence is higher in children, an adequate balance on major mite species and major allergens must be consider in the design of mite allergy

Carmine is a natural red dye widely used as a food coloring agent and for cosmetic manufacture. It is extracted from the dried females of the insect Dactylopius coccus var. Costa (cochineal). Although it has been reported that inhalation of carmine may give rise to occupational asthma and extrinsic allergic alveolitis, there is little evidence of its immunogenic capacity. We studied nine current employees at a factory making natural dyes and one former employee who had left this plant after occupational asthma developed. A current employee had work-related symptoms of rhinitis and asthma that were confirmed by bronchial provocation tests, and another worker had rhinitis. Immunologic sensitization to carmine and cochineal was evaluated by means of skin testing and determination of serum-specific IgE and IgG subclass antibodies by RAST and ELISA, respectively. The specificity of the RAST assay was investigated by RAST inhibition with different fractions of carmine. The three workers with respiratory symptoms had positive skin prick test reactions to both carmine and cochineal. An immediate response to the bronchial provocation test with carmine and cochineal was observed in the current employee with asthma. Specific IgE antibodies against carmine and cochineal were found only in this worker. RAST inhibition studies indicated that the main allergen had a molecular weight between 10 and 30 kd. Specific IgG antibodies against carmine and cochineal, mainly the subclasses IgG1, IgG3, and IgG4, were found in the 10 subjects surveyed. These findings suggest that carmine may induce immunologic responses, most likely IgE mediated in workers with symptoms of occupational asthma.

Introduction: The conventional schedule used in specific subcutaneous immunotherapy (SCIT) is a slow treatment that often leads to poor compliance or discontinuation of treatment. These disadvantages have led to design administration schedules that shorten the build-up phase without increasing the adverse reactions rate. Areas covered: This report reviews the available scientific documentation of the safety profile of build-up schedules for SCIT with Alustal Rapid® (a suspension of standardized allergen extracts adsorbed on aluminum hydroxide gel for specific immunotherapy) in the treatment of IgE-mediated rhinitis, conjunctivitis and bronchial asthma to inhaled allergens. Expert opinion: Cluster and shortened conventional schedules may offer a safe method of SCIT for the treatment of respiratory allergy and reduce the inconvenience associated with conventional schedules by reaching the maintenance dose in less time and with fewer visits; thereby this method could reduce discontinuation rates and increase...

We evaluated the safety of immunotherapy in 419 patients who attended our allergy department for treatment. They were suffering from rhinitis and asthma caused by sensitization to grass pollen or Dermatophagoides pteronyssinus. Immunotherapy was given by biologically standardized aluminum hydroxide adsorbed extracts according to a conventional schedule. Local reactions were recorded in 10.5% of the patients and systemic reactions in 4.8%. Only 0.37% of the doses administered were associated with systemic side-effects. We found that 84% of the patients who showed systemic reactions were asthmatic subjects (P < 0.01), and most of them were sensitized to D. pteronyssinus (71%). Side-effects occurred more frequently during the dose-increase period (P < 0.05). After 9482 doses had been administered, no anaphylactic shock or life-threatening reactions were registered. We believe the risk associated with immunotherapy to be drastically reduced when treatment is carefully monitored by skilled personnel. In such conditions, as shown by our study, immunotherapy is safe.

Summary Background Allergy diagnosis needs to be improved in patients suffering from pollen polysensitization due to the existence of possible confounding factors in this type of patients. Objective To evaluate new diagnostic strategies by comparing skin responses to pan-allergens and conventional allergenic extracts with specific IgE (sIgE) to purified allergen molecules. Methods One thousand three hundred and twenty-nine pollen-allergic patients were diagnosed by a combination of an in vitro method with a panel of 13 purified allergens, including major allergens and pan-allergens, using a high-capacity screening technology (ADVIA-Centaur®) and skin prick test (SPT) to pan-allergens and conventional extracts. Results There was a high concordance (κ index) between in vitro (sIgE to major allergens) and in vivo (SPT to conventional extracts) methods in patients who were not sensitized to pan-allergens, but SPT with conventional extracts failed to diagnose patients with sensitization to pan-allergens. In patients who were simultaneously sensitized to polcalcins and profilins, there was a duplication both in the number of sensitizations to major allergens and in the years of disease evolution. There was a statistical association between sensitization to profilins and/or lipid transfer proteins and food allergy (P

BACKGROUND: The efficacy and safety of the 300-index of reactivity (IR) dose of 5-grass-pollen sublingual immunotherapy (SLIT) tablets (Stallergènes, Antony, France) have been demonstrated for the treatment of hay fever in adults.OBJECTIVE: We sought to assess the efficacy and safety of this tablet in children and adolescents with grass pollen-related allergic rhinitis.METHODS: In this multinational, randomized, double-blind, placebo-controlled study, 278 children (5-17 years of age) with grass pollen-related rhinoconjunctivitis (confirmed by means of a positive grass pollen skin prick test response and serum-specific IgE measurement) received once-daily SLIT tablets or placebo. Treatment was initiated 4 months before the estimated pollen season and continued throughout the season. The primary outcome was the rhinoconjunctivitis total symptom score (RTSS), a sum of 6 individual symptom scores: sneezing, runny nose, itchy nose, nasal congestion, watery eyes, and itchy eyes. Secondary end points included rescue medication intake, individual scores, and safety.RESULTS: The intent-to-treat population included 266 children (mean age, 10.9 +/- 3.22 years). The RTSS for the 300-IR group was highly significantly different from that of the placebo group (P = .001). The 300-IR group showed a mean improvement for the RTSS of 28.0% over that seen with placebo and a median improvement of 39.3%. Significant differences between the 300-IR and placebo groups were also observed regarding rescue medication score and proportion of days using rescue medication during the pollen season (P = .0064 and P = .0146, respectively). Adverse events were generally mild or moderate in intensity and expected. No serious side effects were reported.CONCLUSION: Five-grass-pollen SLIT tablets (300 IR) reduce both symptom scores and rescue medication use in children and adolescents with grass pollen-related rhinoconjunctivitis.

Fundamento: Los tatuajes de henna natural marrón/rojo, obtenida del arbusto indígena Lawsonnia, se llevan realizando tradicionalmente con escasos efectos secundarios. Actualmente se utilizan tatuajes de henna negra (denominados tatuajes temporales o pseudotatuajes), incluso en niños. Debido a los agentes químicos añadidos para mejorar sus propiedades estos tatuajes tienen alto poder sensibilizante y causan dermatitis de contacto. Nuestro objetivo es determinar los agentes causantes de dermatitis de contacto tras pseudotatuaje en dos niños. Material y métodos: Caso 1: Niña de 12 años, sin atopia, presentó vesículas locales a las 10 horas de tatuaje de henna negra. Tatuaje previo con igual sintomatología. Caso 2: Niño de 7 años, atópico, presentó a las 2 semanas de tatuaje con henna negra vesiculación en zonas de contacto. Antecedente de tinción de pelo sin incidencias. Ambos curaron a las 3-4 semanas de tratamiento quedando hipopigmentación residual. Se realizó prick con henna natural y comercial, y pruebas epicutáneas con la batería estándar de contactantes y las baterías de compuestos del grupo para derivados del ácido para-aminobenzoico (PABA) y colorantes textiles así como henna natural y comercial. Resultados: Las pruebas epicutáneas mostraron resultados positivos con p-Metilaminofenol, p-Aminobenceno, p-Fenilendiamina y p-Toluenodiamina en ambos pacientes. Además, la paciente 1 tuvo positividades con benzocaína, hidroquinona, isobutil p-aminobenzoato, Amarillo 1 y Naranja 1 dispersos, y el paciente 2 con Rojo 1 y Naranja 1 dispersos. En ambos casos el prick y las pruebas epicutáneas con henna fueron negativas. Conclusión: Los dos niños presentados sufrieron dermatitis de contacto tras tatuaje de henna negra debido a los aditivos añadidos a la henna natural, como la parafenilendiamina.

Background: Allergy to natural rubber latex proteins continues to be an important medical problem among health care professionals, but also in multioperated children. Clinical manifestations range from urticaria to angioedema, rhinoconjunctivitis, bronchial asthma and anaphylactic shock. Methods: The aim of this study was to investigate the efficacy and safety of a 12-month latex-specific immunotherapy in sensitized patients, most often health care workers. Twenty-three patients with latex rhinoconjunctivitis (20 of whom also had asthma) were included in this randomized, double-blind, placebo-controlled trial (11 in the active group, 12 in the placebo group). Treatment efficacy was assessed by means of symptom and medication scores. Conjunctival provocation tests and quantitative skin prick tests were also performed. Results: The clinical index (derived by combining changes from baseline of six efficacy variables during the treatment period) did not differ significantly between treatment groups. Change from baseline of rhinitis, conjunctivitis, skin symptoms, asthma symptoms, medication score and cutaneous reactivity were not significantly different between the two groups. A nonsignificant difference in conjunctival reactivity was observed in favor of the active group (p = 0.09). Systemic reactions were much higher in the specific immunotherapy than in the placebo group. Conclusions: The present study failed to show a significant improvement of symptoms and medication scores, probably because of the low level of symptoms at baseline and the low maintenance dose of therapy, even if allergen-specific conjunctival reactivity decreased in the active group. Moreover, the incidence of systemic reactions was very high in the active group.

Background: Treatment regimens with specific immunotherapy include updosing. Due to excellent tolerance of sublingual immunotherapy (SLIT), it was hypothesized that administration of once-daily SLIT could be initiated safely without updosing. The objective was to evaluate tolerability of SLIT administered once daily without updosing. Methods: 135 patients suffering from allergic rhinitis with/without asthma were included in a double-blind, placebo-controlled, parallel-group study. Patients were randomized into two groups. Group 1 (n = 69) received active treatment throughout the study, including 10 days updosing (T1), 20 days maintenance treatment (T2), and 2 consecutive months on maintenance treatment (T3 and T4). Group 2 (n = 66) obtained placebo updosing (T1), placebo maintenance (T2), initiated active treatment (maintenance) at T3, and continued active treatment until the end of the study (T4). Adverse events (AEs) were assessed at T1–T4. 66 grass- and 69 mite-allergic patients were evenly distributed between groups. Results: 229 AEs were reported, 157 AEs were related to treatment. The most frequently reported AEs (>5% of patients in any group) related to treatment were oral itching, ocular itching, rhinitis, and sublingual edema. For group 1 at T2, the rate of all AEs related to treatment per dose administered was 1.79%, and for group 2 at T3 the rate was 1.33% (p = 0.37). For the most frequently reported AE, oral itching, the rate per dose administered was 1.01% for group 1 at T2, and 0.74% for group 2 at T3 (p = 0.53). Conclusions: Once daily SLIT was well tolerated and can be safely initiated without updosing.

Summary Background Asparagus (Asparagus officinalis) is an extensively grown and consumed vegetable. To a lesser extent than other Liliaceae vegetables, allergic contact dermatitis (ACD) due to asparagus has been reported. However, only a few case reports of asparagus IgE-mediated allergy have been published. In a previous study, we demonstrated that two lipid transfer proteins (LTPs) (Aspa o 1.01 and Aspa o 1.02) were relevant allergens of asparagus. Objective We retrospectively analysed the 27 patients diagnosed with asparagus allergy during the last 5 years. All of them reported adverse symptoms after either asparagus ingestion or handling. We describe their clinical features and evaluate whether they were associated to immunological findings (immunoblot pattern and skin reactivity to LTPs). Methods Patients underwent skin prick and patch tests with standard panels of vegetables and aeroallergens. Besides crude asparagus extract, two purified LTPs were prick and patch tested. Total and specific IgE measurements and asparagus extract IgE immunoblotting were performed. Patients reporting asthma symptoms underwent specific inhalation challenge to asparagus. Results Of the 27 subjects, eight had ACD, 17 had IgE-mediated allergy and two had both ACD- and IgE-mediated allergy. Positive patch tests with the crude asparagus extract but not with LTPs were observed in subjects with ACD (n=10). Of 19 patients with IgE-mediated disease, 10 had contact urticaria after asparagus handling. Of them, five subjects and five others without skin allergy showed respiratory symptoms; of them, eight were diagnosed with occupational asthma confirmed by positive asparagus inhalation challenge, whereas the remaining two had isolated rhinitis. Four patients suffered from immediate allergic reactions related to asparagus ingestion (food allergy); three of them reported anaphylaxis whereas the other had oral allergic syndrome. Positive IgE immunoblotting (bands of 15 and 45–70 kDa) was observed in 10 subjects. Of 10 subjects with positive prick test to LTPs, six showed bands at 15 kDa. Either IgE-binding bands or positive prick tests to LTPs were observed in asthma (62%) and anaphylaxis (67%). Conclusion Asparagus is a relevant source of occupational allergy inducing ACD and also IgE-mediated reactions. Severe disease (anaphylaxis or asthma) is common and LTPs seem to play a major role. The clinical relevance of LTP sensitization among patients with mild disease or symptom-free subjects should be addressed in prospective studies.

In recent years the study of samples of bronchial biopsies and bronchoalveolar lavage fluid has made it possible to show the existance of significant airway mucosal inflammation, even in cases of mild bronchial asthma. This has led to a renewed interest in the use of sputum to assess airway inflammation non-invasively. Sputum induction has recently been proposed as a non-invasive alternative to bronchoscopy for the collection of airway secretions from asthmatic subjects. Sputum induction yields satisfactory samples of sputum in the great majority of asthmatic subjects, and both differential cell counts and the measurement of molecular markers of inflammation in the sputum fluid phase are feasible. In this paper we review studies where these measurements have been taken from subjects who were asthmatic, affected by other respiratory pathologies or healthy, and we assess their validity. Finally, we consider possible future clinical applications of sputum measurement of airway inflammation in asthma.

El espárrago (Asparagus officinalis), ampliamente cultivado a escala mundial, forma parte, junto con el ajo, la cebolla y el puerro de la familia de Liliáceas. Se ha descrito hipersensibilidad al espárrago en forma de reacciones retardadas mediadas por células, y de reacciones inmediatas mediadas por IgE. Mientras que las primeras (dermatitis alérgica de contacto) son una causa relativamente frecuente de patología ocupacional, la literatura sólo muestra casos puntuales de alergia IgE mediada. Las reacciones mediadas por IgE ocurren principalmente en individuos atópicos y se pueden clasificar en alergia alimentaria y reacciones secundarias a la exposición cutánea o inhalada, generalmente ocupacional, a proteínas del espárrago. La manifestación clínica más frecuente de la alergia alimentaria es la anafilaxia mientras que en las segundas, la urticaria de contacto, la rinitis y el asma ocupacional pueden coexistir o aparecer aisladas. La diferente forma de presentación clínica de las reacciones mediadas por IgE es probablemente consecuencia de la sensibilización a diferentes alergenos. La importancia de la detección y el diagnóstico diferencial de estas manifestaciones radica en su diferente tratamiento y pronóstico. En este artículo revisamos nuestra experiencia en los últimos 5 años.