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Kowalski M.L.,Medical University of Lódz | Asero R.,Ambulatorio di Allergologia | Bavbek S.,Ankara University | Blanca M.,Carlos Haya Hospital | And 15 more authors.
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2013

Hypersensitivity reactions to aspirin (acetylsalicylic acid) and other nonsteroidal anti-inflammatory drugs (NSAIDs) constitute only a subset of all adverse reactions to these drugs, but due to their severity pose a significant burden to patients and are a challenge to the allergist. In susceptible individuals, NSAIDs induce a wide spectrum of hypersensitivity reactions with various timing, organ manifestations, and severity, involving either immunological (allergic) or nonimmunological mechanisms. Proper classification of reactions based on clinical manifestations and suspected mechanism is a prerequisite for the implementation of rational diagnostic procedures and adequate patient management. This document, prepared by a panel of experts from the European Academy of Allergy and Clinical Immunology Task Force on NSAIDs Hypersensitivity, aims at reviewing the current knowledge in the field and proposes uniform definitions and clinically useful classification of hypersensitivity reactions to NSAIDs. The document proposes also practical algorithms for the diagnosis of specific types of NSAIDs hypersensitivity (which include drug provocations, skin testing and in vitro testing) and provides, when data are available, evidence-based recommendations for the management of hypersensitive patients, including drug avoidance and drug desensitization. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


Vejvar E.,Christian Doppler Laboratory | Himly M.,Christian Doppler Laboratory | Briza P.,Christian Doppler Laboratory | Eichhorn S.,Christian Doppler Laboratory | And 4 more authors.
Molecular Nutrition and Food Research | Year: 2013

Scope: Apium graveolens represents a relevant food allergen source linked with severe systemic reactions. We sought to identify an IgE-binding nonspecific lipid transfer protein (nsLTP) in celery tuber. Methods and results: A low molecular weight protein exclusively present in celery tuber was purified and designated Api g 6. The entire protein sequence was obtained by MS and classified as member of the nsLTP2 family. Api g 6 is monomeric in solution with a molecular mass of 6936 Da. The alpha-helical disulfide bond-stabilized structure confers tremendous thermal stability (Tm > 90°C) and high resistance to gastrointestinal digestion. Endolysosomal degradation demonstrated low susceptibility and the presence of a dominant peptide cluster at the C-terminus. Thirty-eight percent of A. graveolens allergic patients demonstrated IgE reactivity to purified natural Api g 6 in ELISA and heat treatment did only partially reduce its allergenic activity. No correlation in IgE binding and limited cross-reactivity was observed with Api g 2 and Art v 3, nsLTP1 from celery stalks and mugwort pollen. Conclusion: Api g 6, a novel nsLTP2 from celery tuber represents the first well-characterized allergen in this protein family. Despite similar structural and physicochemical features as nsLTP1, immunological properties of Api g 6 are distinct which warrants its inclusion in molecule-based diagnosis of A. graveolens allergy. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Holzweber F.,Das Labor | Svehla E.,University of Natural Resources and Life Sciences, Vienna | Fellner W.,Kwizda Epignost | Dalik T.,University of Natural Resources and Life Sciences, Vienna | And 3 more authors.
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2013

Background Allergy diagnosis by determination of allergen-specific IgE is complicated by clinically irrelevant IgE, of which the most prominent example is IgE against cross-reactive carbohydrate determinants (CCDs) that occur on allergens from plants and insects. Therefore, CCDs cause numerous false-positive results. Inhibition of CCDs has been proposed as a remedy, but has not yet found its way into the routine diagnostic laboratory. We sought to provide a simple and affordable procedure to overcome the CCD problem. Methods Serum samples from allergic patients were analysed for allergen-specific IgEs by different commercial tests (from Mediwiss, Phadia and Siemens) with and without a semisynthetic CCD blocker with minimized potential for nonspecific interactions that was prepared from purified bromelain glycopeptides and human serum albumin. Results Twenty two per cent of about 6000 serum samples reacted with CCD reporter proteins. The incidence of anti-CCD IgE reached 35% in the teenage group. In patients with anti-CCD IgE, application of the CCD blocker led to a clear reduction in read-out values, often below the threshold level. A much better correlation between laboratory results and anamnesis and skin tests was achieved in many cases. The CCD blocker did not affect test results where CCDs were not involved. Conclusion Eliminating the effect of IgEs directed against CCDs by inhibition leads to a significant reduction in false-positive in vitro test results without lowering sensitivity towards relevant sensitizations. Application of the CCD blocker may be worthwhile wherever natural allergen extracts or components are used. © 2013 The Authors. Allergy published by John Wiley & Sons Ltd.


Hemmer W.,Floridsdorf Allergy Center | Focke M.,Medical University of Vienna | Marzban G.,University of Natural Resources and Life Sciences, Vienna | Swoboda I.,Medical University of Vienna | And 2 more authors.
Clinical and Experimental Allergy | Year: 2010

Background: Allergy to fig fruit (Ficus carica) has been described in patients allergic to Ficus benjamina or rubber latex but may occur also in pollen-allergic patients. Objective: To study the potential cross-reactivity between fig and taxonomically related fruits with the major birch pollen allergen Bet v 1. Methods: One hundred and eighty-eight patients with or without birch pollen allergy were prick-to-prick tested with fig (F. carica), mulberry (Morus alba), jackfruit (Artocarpus heterophyllus; all family Moraceae) and other pollen-associated foods. Moraceae fruit extracts were separated by SDS-PAGE and tested with patient sera and polyclonal antisera against Mal d 1. Western blot inhibition was performed with Moraceae fruit extracts, birch pollen and recombinant Bet v 1. Putative Bet v 1 homologs in Moraceae fruits were analysed by liquid chromatography-ion trap mass spectrometry. Results: Among 85 patients with isolated birch pollen allergy, 78% had a positive skin test to fresh fig, 10% to dried fig, 91% to mulberry, 91% to jackfruit, 77% to Rosaceae fruits and 83% to hazelnut. Sixty-six per cent of birch pollen-allergic patients positive for fig, reported symptoms after consumption of fresh figs, whereas dried figs were mostly well tolerated. In 60 patients with isolated Ficus benjamina sensitization, the reactivity rates to the same foods were 83-40-0-0-0-0%. None of 32 mugwort pollen-allergic patients reacted to Moraceae fruits. Rabbit anti-Mal d 1 and patient sera reacted to a 17 kDa band in all Moraceae extracts. IgE binding to these proteins was completely inhibited by birch pollen and rBet v 1. Mass spectrometry identified several peptides from the 17 kDa fig, mulberry and jackfruit allergen with respectively 60%, 56% and 76% homology to Bet v 1. Conclusion: Fig and other Moraceae fruits contain allergens homologous to Bet v 1 and represent clinically relevant birch pollen-associated foods. © 2010 Blackwell Publishing Ltd.


Konakovsky V.,Floridsdorf Allergy Center | Focke M.,Medical University of Vienna | Hoffmann-Sommergruber K.,Medical University of Vienna | Schmid R.,Medical University of Vienna | And 4 more authors.
Food Additives and Contaminants - Part A Chemistry, Analysis, Control, Exposure and Risk Assessment | Year: 2011

Biogenic amines in wine may impair sensory wine quality and cause adverse health effects in susceptible individuals. In this study, histamine and other biogenic amines were determined by HPLC after amine derivatisation to dansyl chloride conjugates in 100 selected high-quality red wines made from seven different cultivars. Amine levels varied considerably between different wines. The most abundant amines were putrescine (median=19.4mg l-1, range=2.9-122), histamine (7.2 mg l-1, 0.5-26.9), and tyramine (3.5 mgl-1, 1.1-10.7), whereas lower levels were found for isoamylamine (median=0.25 mgl-1), phenylethylamine (0.16 mg l-1), cadaverine (0.58 mg l-1), spermidine (1.8 mg l-1) and tryptamine (0.06 mg l-1). Positive correlations were observed between isoamylamine and phenylethylamine, and between histamine, putrescine and tyramine levels. Amine concentrations were similar in all wine cultivars except Pinot noir and St. Laurent wines, which showed significantly higher tryptamine and cadaverine levels. The results indicate that levels of histamine and other biogenic amines may vary considerably between red wines independent of grape variety and that high amounts can also be found in high-rated wines. Adopting a legal histamine threshold level of 10 mgl-1 in the European Union, as formerly introduced in other countries, would have excluded 34% of the investigated wines from the market. © 2011 Taylor & Francis.


Sturm G.J.,Medical University of Graz | Kranzelbinder B.,Medical University of Graz | Schuster C.,Medical University of Graz | Sturm E.M.,Medical University of Graz | And 5 more authors.
Journal of Allergy and Clinical Immunology | Year: 2014

Background Sensitization to Hymenoptera venom without systemic sting reactions (SSRs) is commonly observed in the general population. Clinical relevance for a future sting has not yet been investigated. Objective We aimed to evaluate the effect of these debatable sensitizations with deliberate sting challenges and to monitor serologic changes for up to 2 years. Methods One hundred thirty-one challenges with bees and wasps were performed in 94 subjects with a hitherto irrelevant sensitization. The clinical outcome was recorded, and results of specific IgE (sIgE) determinations, skin tests, and basophil activation tests were correlated to the sting reaction. sIgE levels were monitored in reactors and nonreactors after 3 hours, 1 week, 4 weeks, and 1 year. Results Only 5 (5.3%) patients had SSRs, but 41 (43.6%) had large local reactions (LLRs) after the sting. Compared with the general population, there was a 9.5-fold higher risk for LLRs but not for SSRs. Three hours after the sting, sIgE levels slightly decreased, but none of the 94 subjects' results turned negative. After 1 week, sIgE levels already increased, increasing up to 3.5-fold (range, 0.2- to 34.0-fold) baseline levels after 4 weeks. To assess the clinical relevance of this increase, we randomly selected 18 patients for a re-sting. Again, 50% had an LLR, but none had an SSR. Conclusion Although sensitization to Hymenoptera venoms was common, the risk of SSRs in sensitized subjects was low in our study. The sIgE level increase after the sting was not an indicator for conversion into symptomatic sensitization. Currently available tests were not able to distinguish between asymptomatic sensitization, LLRs, and SSRs. © 2014 American Academy of Allergy, Asthma & Immunology.


Jin C.,University of Natural Resources and Life Sciences, Vienna | Focke M.,Medical University of Vienna | Leonard R.,University of Natural Resources and Life Sciences, Vienna | Jarisch R.,Floridsdorf Allergy Center | And 2 more authors.
Journal of Allergy and Clinical Immunology | Year: 2010

Background: Yellow jacket hyaluronidase (YJ-HYA) is considered a major allergen in yellow jacket allergy. It shows 50% homology with the hyaluronidase from honeybee venom, Api m 2. Recently, IgE binding to YJ-HYA and cross-reactivity with Api m 2 has been shown to be due to cross-reactive carbohydrate determinants (CCDs). Objective: We sought to quantify the importance of YJ-HYA in yellow jacket allergy and the cross-reactivity with Api m 2 by discriminating between carbohydrate and peptide epitopes. Methods: IgE binding to Vespula species venom was studied by means of Western blotting in 136 patients with yellow jacket allergy (31 in vitro single positive to yellow jacket venom and 105 in vitro double-positive to yellow jacket-honeybee). Inhibition studies were carried out with MUXF-BSA (isolated bromelain glycopeptides linked to bovine serum albumin) and purified Api m 2. Results: Among yellow jacket single-positive sera, only 1 of 31 bound with YJ-HYA, whereas this was the case in 87% of 105 double-positive sera. Of 83 patients in whom inhibitions were performed, 65% reacted with hyaluronidase through CCDs alone, 27% reacted with both CCDs and peptide epitopes, and 8% reacted only with the hyaluronidase peptide. The protein-specific reactivity with YJ-HYA was cross-inhibited by Api m 2 in 48% (14/29). Antigen 5 and phospholipase A1 were each recognized by around 90% of sera from both groups, together identifying 97% of patients. Conclusion: Hyaluronidase is a minor yellow jacket venom allergen, and only 10% to 15% of patients with yellow jacket allergy are estimated to have IgE against the hyaluronidase protein. Peptide-specific cross-reactivity with Api m 2 occurs in half of these sera. Component-resolved diagnosis with antigen 5 and phospholipase would detect virtually all patients with yellow jacket venom allergy. © 2010 American Academy of Allergy, Asthma & Immunology.


Bokanovic D.,Medical University of Graz | Aberer W.,Medical University of Graz | Hemmer W.,Floridsdorf Allergy Center | Heinemann A.,Medical University of Graz | And 3 more authors.
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2013

Background New diagnostic tools such as the basophil activation test (BAT) and component-resolved diagnosis (CRD) are promising for hymenoptera venom or food allergy. A clear benefit for inhalant allergens has not yet been shown. Our aim was to compare new and established tests for grass pollen allergy. Methods Forty-nine patients with grass pollen allergy and 47 controls were prospectively enrolled in the study. A symptom score was calculated for each patient. Conjunctival provocation tests (CPT), skin prick tests (SPT), BAT, and sIgE determination including CRD were performed. Sensitivity and specificity were compared and results were correlated with the symptom score. Results Single determination of sIgE to rPhl p 1 showed the best balance between sensitivity (98%) and specificity (92%). Use of additional components, such as rPhl p 2 and 5, did not increase sensitivity. Generally, sensitivity of tests was high: SPT 100%, ISAC-112 100%, sIgE to timothy grass 98%, BAT 98%, ISAC-103 84%, and CPT 83%. Specificity ranged from 79% (SPT) to 96% (CPT). All test results and calculated values (e.g. ratio sIgE/tIgE) did not correlate with symptom severity. Asymptomatic sensitization to timothy grass in controls was rare in the CAP (11%) and predominantly due to Phl p 1 sensitization. Conclusion rPhl p 1 was sufficient to diagnose grass pollen allergy, and sIgE patterns were the same in symptomatically and asymptomatically sensitized subjects. The testing of multiple components was of minor importance, and no test correlated with symptom severity. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


Guhsl E.E.,Medical University of Vienna | Hofstetter G.,Medical University of Vienna | Lengger N.,Medical University of Vienna | Hemmer W.,Floridsdorf Allergy Center | And 6 more authors.
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2015

Background Birch pollen-associated plant food allergy is caused by Bet v 1-specific IgE, but presence of cross-reactive IgE to related allergens does not predict food allergy. The role of other immunoglobulin isotypes in the birch pollen-plant food syndrome has not been investigated in detail. Methods Bet v 1-sensitized birch pollen-allergic patients (n = 35) were diagnosed for food allergy by standardized interviews, skin prick tests, prick-to-prick tests and ImmunoCAP. Concentrations of allergen-specific IgE, IgG1, IgG4 and IgA to seven Bet v 1-related food allergens were determined by ELISA. Results Bet v 1, Cor a 1, Mal d 1 and Pru p 1 bound IgE from all and IgG4 and IgA from the majority of sera. Immunoglobulins to Gly m 4, Vig r 1 and Api g 1.01 were detected in <65% of the sera. No significant correlation was observed between plant food allergy and increased or reduced levels of IgE, IgG1, IgG4 or IgA specific to most Bet v 1-related allergens. Api g 1-specific IgE was significantly (P = 0.01) elevated in celeriac-allergic compared with celeriac-tolerant patients. Likewise, frequencies of IgE (71% vs 15%; P = 0.01) and IgA (86% vs 38%; P = 0.04) binding to Api g 1.01 were increased. Conclusion Measurements of allergen-specific immunoglobulins are not suitable for diagnosing Bet v 1-mediated plant food allergy to hazelnut and Rosaceae fruits. In contrast, IgE and IgA to the distantly related allergen Api g 1 correlate with allergy to celeriac. © 2014 The Authors. Allergy Published by John Wiley & Sons Ltd.


Jarisch R.,Floridsdorf Allergy Center
Histamine Intolerance: Histamine and Seasickness | Year: 2015

Histamine is an important mediator of allergic diseases, but knowledge of histamine as a cause of numerous non-allergic symptoms and signs is limited. This book offers wide-ranging coverage of histamine intolerance. There is extensive background discussion of the origin of histamine, its content in food and alcoholic beverages and intolerance to red wine. Diagnosis of histamine intolerance is explained and the various symptoms of histamine intolerance are clearly described. Subsequent chapters cover the relation of histamine to a wide variety of conditions, including drug intolerance, atopic dermatitis, seasickness and osteoporosis. This book will prove of value in clinical practice by facilitating differential diagnosis, which is by no means straightforward given the multiplicity of symptoms of histamine intolerance and by assisting in the selection of therapeutic measures. © Springer-Verlag Berlin Heidelberg 2015.

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