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BACKGROUND: A genetic defect in the epidermal barrier protein filaggrin plays a major role in the etiology of eczema and associated allergic airways diseases. However, it is still controversial to what extend loss-of-function (LOF) mutations in the filaggrin gene (FLG) contribute to the development and persistence of food allergies.OBJECTIVE: We tested association of FLG LOF mutations with allergic reactions to diverse foods and investigated their potential effect on the persistence of early food allergies. METHODS: We recruited 890 children with challenge-proven food allergy for the German Genetics of Food Allergy Study (GOFA). Longitudinal data were available for 684 children. All children were clinically characterized, including their allergic responses to specific foods, and genotyped for the four most common LOF mutations in FLG; R501X, 2282del4, R2447X, and S3247X. Associations between FLG mutations and food allergies were analyzed by logistic regression using the German Multicenter Allergy Study cohort as control population. RESULTS: FLG mutations were associated with allergies to diverse foods including hen's egg (HE), cow's milk (CM), peanut, hazelnut, fish, soy, cashew, walnut, and sesame with similar risk estimates. Effects remained significant after adjusting for the eczema status. Interestingly, FLG mutations increased the risk of a persistent course of HE and CM allergy. CONCLUSION: Using the gold standard for food allergy diagnosis, we demonstrate that FLG LOF mutations confer a risk of any food allergy independent of eczema. They predispose to the persistence of HE and CM allergy and should be considered in the assessment of tolerance development.

Aim of our prospective, multicenter, nonrandomized study was to identify characteristic features and similarities of patients with functional respiratory disorders regarding socio-familial and behavioral aspects, in comparison with controls in a cross-sectional analysis using standardized psychological questionnaires. Furthermore, we investigated the longitudinal outcome of symptoms, effects of primary interventions and the stability of psychological traits 6 months after diagnosis and primary intervention.Initially, 106 patients (68 females, 27 males) and 58 controls (33 females, 25 males) were recruited for the study. Mean age was 12.6 years in patients and 11.9 years in controls.The child behavior checklist (CBCL) showed significantly increased scores for anxious/depressed (p = 0.002) and schizoid/obsessive (p = 0.001) behavior in patients. A trend was evident for internalizing behavior (p = 0.009) and for a higher total score (p = 0.008). In the self-assessment youth self-report (YSR), there was a trend towards higher values for anxious/depressed behavior in patients (p = 0.06) and towards more externalizing behavior (p = 0.029) in the control group. After 6 months, 31% of the patients were free of symptoms, 42% had improved. For themselves, parents reported a decreased burden from 56% to 23% (p 0.001) and decreased impairment from 57% to 30% (p 0.008). For their children, parents reported a decrease from 45% to 16% (p 0.0001) and from 74% to 37% (p 0.0001), respectively. A longitudinal comparison from T1 to T2 showed no statistically significant changes in all three psychological questionnaires (CBCL, YSR, and SOMS-KJ).In summary, we show that patients with functional respiratory disorders differ from healthy subjects, with internalizing behavior being a characteristic trait. The outcome in terms of symptoms, perceived psycho-familial burden and impairment after 6 months is encouraging. However, we are aware that our preliminary data offer thought-provoking impulses rather than firm findings.

It has been reported that sometimes children fall asleep and can barely be woken up during allergic reactions on food ingestion. Nevertheless, to date, there is scarce data on narcolepsy-like sleepiness as a symptom of allergic reactions.To investigate the frequency of narcolepsy-like sleepiness during oral food challenges and characterize this symptom regarding comorbidities, eliciting allergens, and severity of reactions.Children with immediate-type allergic reactions during oral food challenges (89% were double-blind, placebo-controlled) have been analyzed in this study. Narcolepsy-like sleepiness was defined as a somnolent condition during which patients could barely be woken up again, occurring within 2 hours of food intake and which was not due to drug side effects. Logistic generalized estimating equations were used to explore the effect of age, severity of reactions, and eliciting allergens on the occurrence of narcolepsy-like sleepiness.In 106 (12.5%) of all 848 food-allergic children, narcolepsy-like sleepiness was observed during oral food challenges. Children with eczema had a higher risk of developing narcolepsy-like sleepiness (P = .006). Narcolepsy-like sleepiness occurred most often due to an allergic reaction to hazelnut (P = .009) or other tree nuts (P = .003). Moderate to severe reactions occurred more often than mild reactions (P = .026; odds ratio, 1.521; 95% CI, 1.051-2.202) in children with narcolepsy-like sleepiness.We were able to show for the first time that narcolepsy-like sleepiness is a frequently occurring clinical manifestation of immediate-type allergic reactions on food ingestion in childhood. Further research is needed to unravel the underlying mechanisms to gain a deeper insight into this underestimated symptom.

Peanut and tree nut allergies are common in childhood and often severe in nature. The clinical picture shows a wide variety of symptoms.To analyze the distribution of clinical symptoms and severity during oral food challenges (OFC) in children.Analysis of 1.013 prospectively recorded, positive OFCs with peanut (n = 607), hazelnut (n = 266), walnut (n = 97), and cashew (n = 43). Symptoms were categorized as immediate-type skin, gastrointestinal, upper and lower respiratory, cardiovascular symptoms, and eczema exacerbation. Symptom severity and treatment were recorded.Skin symptoms presented in 78%, followed by gastrointestinal (47%), upper (42%), and lower respiratory symptoms (32%). Cardiovascular symptoms presented in 6%. In three-quarter of the reactions, more than one organ was involved. Importantly, severe reactions occurred at every dose level. Peanut- and cashew-allergic patients had a higher relative risk of gastrointestinal symptoms compared with hazelnut- and walnut-allergic patients. Patients without vomiting had a 1.7 times higher risk developing immediate-type skin and/or lower respiratory symptoms. Three-quarter of the patients ever had eczema but worsening presented in only 10.5% of the OFCs. In patients with multiple food allergies, organs involved, eliciting dose and severity differed between allergens.Although comparisons between allergen groups with different clinical history, severity, comorbidities and laboratory data are difficult and might contain bias, our data confirm the high allergenic potential of peanut and tree nuts. The rare occurrence of eczema worsening emphasizes that avoidance diets of peanuts and tree nuts to cure eczema seem to be unnecessary and may hamper tolerance maintenance.

Background It has previously been shown in an uncontrolled study that the IgE response to vaccine antigens is downregulated by co-vaccination with cellular Bordetella pertussis vaccine. Methods In the present study, we compared in a controlled trial the humoral immune response to diphtheria toxoid (D) and tetanus toxoid (T) in relation to co-vaccinated cellular or acellular B pertussis vaccine. IgE, IgG4, and IgG to D and T were analyzed at 2, 7, and 12 months of age in sera of children vaccinated with D and T (DT, N = 68), cellular (DTPw, N = 68), 2- or 5-component acellular B pertussis vaccine (DTPa2, N = 64; DTPa5, N = 65). Results One month after vaccination, D-IgE was detected in 10% sera of DTPw-vaccinated children, whereas vaccination in the absence of whole-cell pertussis resulted in 50%-60% IgE positivity. Six months after vaccination, the IgE antibody levels were found to be more persistent than the IgG antibodies. These diphtheria findings were mirrored by those for tetanus. Only minor differences between vaccine groups were found with regard to D-IgG and T-IgG. No immediate-type allergic reactions were observed. Conclusion Cellular (but not acellular) B pertussis vaccine downregulates IgE to co-vaccinated antigens in infants. We assume that the absence of immediate-type allergic reactions is due to the high levels of IgG antibodies competing with IgE antibodies.

Background: Numerous products are available for subcutaneous (SCIT) and sublingual allergen-specific immunotherapy, but there are no information about the direct comparability regarding efficacy, safety, and tolerability of the different extracts. Aims: The aim of this open-labelled, prospective, controlled observational trial was to test the feasibility of a comparison of different products for SCIT in children. Methods: Pediatrician practices recruited patients with a confirmed diagnosis of a seasonal allergic rhinoconjunctivitis (AR) with or without asthma and an allergic sensitization against grass pollen allergen. Every patient was offered SCIT with one out of six allergen extracts: ALK SQ Depot, ALK Avanz, Allergovit, Depigoid, Purethal, Pollinex Quattro. Scores for symptoms and medications were calculated and the difference between treatment years and baseline were recorded. Results: In total, 284 were recruited and 255 children (89.8%; mean age 10.4, SD 3.54 years; 65% males) participated in this trial. Overall, 49,649 patient days were recorded in the electronic database (mean 183.2 days/patient). There was no significant difference in the AR and asthma symptom score or the medication score between the six different SCIT preparations. Similarly, no differences were observed in terms of safety and tolerability. Conclusion: The comparison of different SCIT products using an online tool is feasible. Based on our preliminary data, all extracts indicated efficacy; however, larger groups would be necessary to demonstrate superiority or non-inferiority of one specific SCIT product.

Background: Blinded food challenges are considered the current gold standard for the diagnosis of food allergies. We used data from a pan-European multicenter project to assess differences between study centers, aiming to identify the impact of subjective aspects for the interpretation of oral food challenges. Methods: Nine study centers of the EuroPrevall birth cohort study about food allergy recruited 12 049 newborns and followed them for up to 30 months in regular intervals. Intensive training was conducted and every center visited to ensure similar handling of the protocols. Suspected food allergy was clinically evaluated by double-blind, placebo-controlled food challenges using a nine dose escalation protocol. The primary challenge outcomes based on physician's appraisal were compared to documented signs and symptoms. Results: Of 839 challenges conducted, study centers confirmed food allergy in 15.6% to 53.6% of locally conducted challenges. Centers reported 0 to 16 positive placebo challenges. Worsening of eczema was the most common sign when challenged with placebo. Agreement between documented objective signs and the challenge outcome assigned by the physician was heterogeneous, with Cohen's kappa spanning from 0.42 to 0.84. Conclusions: These differences suggest that the comparison of food challenge outcomes between centers is difficult despite common protocols and training. We recommend detailed symptom assessment and documentation as well as objective sign-based challenge outcome algorithms to assure accuracy and comparability of blinded food challenges. Training and supervision of staff conducting food challenges is a mandatory component of reliable outcome data.

Environmental exposure to food allergens may be a risk factor for cutaneous sensitization. Previous studies could detect peanut allergen in house dust. In this pilot study, we wanted to investigate whether hen's egg allergen is detectable in house dust collected from different household areas and whether levels are increased after intentional hen's egg consumption. Hen's egg protein levels of dust samples were measured using ELISA. In 8 of 8 households, hen's egg was detectable in dust samples of eating area and bed. Forty-eight hours after intentional hen's egg consumption, hen's egg protein levels were significantly increased in both. Still, further research is necessary to investigate whether hen's egg allergen in house and bed dust plays a role in sensitization via skin.

Background Microarray-based component-resolved diagnostics (CRD) has become an accepted tool to detect allergen specific IgE-sensitization towards hundreds of allergens in parallel from one drop of serum. Nevertheless specificity and sensitivity as well as a simultaneous detection of allergen specific IgG4, as a potential parameter for tolerance development, remain to be optimized. Objective We applied the recently introduced silicon chip coated with a functional polymer named copoly(DMA-NAS-MAPS) to the simultaneous detection of food allergen specific IgE and IgG4, and compared it with ImmunoCAP and ImmunoCAP ISAC. Inter- and intra- slide variation, linearity of signal and working range, sensitivity and application of internal calibrations for IgE and IgG4 were assessed. Methods Native and recombinant allergenic proteins from hen's egg and cow's milk were spotted on silicon chips coated with copoly(DMA-NAS-MAPS) along with known concentrations for human IgE and IgG4. A serum pool and 105 patient samples were assessed quantitatively and semi-quantitatively with the ImmunoCAP and ImmunoCAP ISAC and correlated with IgE- and IgG4-specific fluorescence on silicon microarrays. Results Allergen specific IgE and IgG4 were detected in parallel using two fluorescent dyes with no crosstalk. Results from the ImmunoCAP correlated better with microarray fluorescence than with ImmunoCAP ISAC except for the allergen ovomucoid. The working range of the silicon microarray for total hen's egg specific IgE was comparable to the range of 0.1 to >100 kUA/l of the ImmunoCAP system, whereas for total cow's milk the silicon microarray was less sensitive. Detectable allergen specific IgG4 could be determined only for low concentrations, but still correlated positively with ImmunoCAP results. Conclusions We confirmed the ability of the polymer coated silicon microarray to be comparably sensitive to the ImmunoCAP ISAC for various food allergens. This suggests that the copoly(DMA-NAS-MAPS) microarray is a low cost, self-producible alternative to the commercial ImmunoCAP ISAC in allergy research. This article is protected by copyright. All rights reserved.

Nahrungsmittelunvertraglichkeiten sind objektiv nachweisbar deutlich seltener als subjektiv empfunden. Insbesondere zum wissenschaftlichen Kenntnisstand nicht allergischer Uberempfindlichkeitsreaktionen bestehen grose Defizite. Ein Beispiel ist die Histaminunvertraglichkeit, die aufgrund der starken Thematisierung in den Medien und im Internet von Betroffenen oftmals als Ausloser ihrer Gesundheitsbeschwerden vermutet wird. Die wissenschaftliche Evidenz fur die postulierten Zusammenhange ist begrenzt, eine verlassliche Laborbestimmung zur definitiven Diagnose nicht vorhanden. Die vorliegende Stellungnahme der Arbeitsgruppe Nahrungsmittelallergie der Deutschen Gesellschaft fur Allergologie und klinische Immunologie (DGAKI) in Zusammenarbeit mit dem Arzteverband Deutscher Allergologen (AeDA), der Padiatrischen Allergologie und Umweltmedizin (GPA) sowie der Schweizerischen Gesellschaft fur Allergologie und Immunologie (SGAI) beleuchtet die Datenlage fur das Krankheitsbild der Unvertraglichkeit gegenuber oral aufgenommenem Histamin, fasst wichtige Aspekte und deren Konsequenzen zusammen und schlagt ein praktikables diagnostisches und therapeutisches Vorgehen vor.

Background Food allergy to pea (Pisum sativum) has been rarely studied in children at the clinical and molecular levels. Objective To elucidate the allergenic relevance and diagnostic value of pea 7S globulin Pis s 1, nsLTP, and 2S albumins PA1 and PA2 in children. Methods Children with pea-specific IgE ≥ 0.35 kUA /L and clinical evidence of pea allergy or tolerance were included in the study. IgE binding against pea total protein extract, recombinant (r) rPis s 1, rPA1, rPA2, and natural nsLTP was analysed using IgE immunoblot/inhibition. Mediator release potency was investigated in passively sensitized rat basophil leukaemia (RBL) 2H3-cells. IgE binding to synthetic overlapping peptides of Pis s 1 was detected on multipeptide microarrays. Results 19 pea-sensitized children were included, 14 with doctors' diagnosed allergy and 5 with tolerance to pea (median age 3.5 and 4.5 years, respectively). 11/14 (78%) pea-allergic and 1/5 (20%) tolerant children were sensitized to Pis s 1. Under the reducing conditions of immunoblot analysis, IgE binding to rPA1 was negligible, sensitization to rPA2 and nsLTP undetectable. Compared to pea total protein extract, rPis s 1 displayed on average 58% IgE binding capacity and a 20-fold higher mediator release potency. Selected Pis s 1-related peptides displayed IgE binding in pea-allergic but not in pea-tolerant children. Conclusions and clinical relevance In this study group, Pis s 1 is a major immunodominant allergen in pea-allergic children. Evidence for sensitization to nsLTP and 2S albumins was low but requires further verification with regard to conformational epitopes. Recombinant Pis s 1 and related peptides which were exclusively recognized by pea-allergic children may improve in vitro diagnosis of pea allergy once verified in prospective studies with larger study groups.

Immunglobulin-E(IgE)-vermittelte Nahrungsmittelallergien im Kindesalter sind haufig. Im Sauglings- und Kleinkindalter sind die primaren Nahrungsmittelallergien vorrangig. Huhnerei ist der haufigste Ausloser, gefolgt von Kuhmilch, Erdnuss, Baumnussen, Weizen, Soja und Fisch. Bei Schulkindern und Jugendlichen spielen pollenassoziierte Nahrungsmittelallergien ebenfalls eine wichtige Rolle. Am haufigsten finden sich Soforttypreaktionen. Die primare Nahrungsmittelallergie kann sich u. a. in Urtikaria, Quincke-Odem, Erbrechen, asthmatischen Symptomen, Stridor und Blutdruckabfall ausern. Bei der pollenassoziierten Nahrungsmittelallergie stehen v. a. die oralen Allergiesymptome im Vordergrund. Ein wichtiger Risikofaktor fur die Entwicklung einer primaren Nahrungsmittelallergie ist die atopische Dermatitis mit ihrer Funktionsstorung der Hautbarriere und einer dadurch begunstigten Sensibilisierung. Praventionsmasnahmen, die zur fruhen oralen Toleranz fuhren, werden zurzeit intensiv untersucht. Neben der Anamnese sind der Nachweis einer Sensibilisierung und ggf. eine orale Nahrungsmittelprovokation diagnostische Bausteine. Therapeutisch steht die Eliminationsdiat an erster Stelle. Patienten mit erhohtem Risiko fur anaphylaktische Reaktionen benotigen einen Adrenalinautoinjektor fur akzidentelle Reaktionen. Instruktion in der Handhabung, schriftliche Anleitung in Form des Anaphylaxiepasses und ausfuhrliche Schulung sollten selbstverstandlich sein. Spezifische Immuntherapien sind zurzeit in der Entwicklung. Die Prognose der Nahrungsmittelallergie ist stark vom Allergen abhangig. Erdnuss- und Baumnussallergien bleiben haufig lebenslang bestehen; dagegen ist die Prognose der Huhnerei- und Kuhmilchallergie gut. Eine regelmasige Reevaluation der Patienten ist notwendig.

Die wichtigste Sofortmasnahme im Rahmen anaphylaktischer Reaktionen ist die Verabreichung von Adrenalin – vorzugsweise i.m. Derzeit gibt es 3 Adrenalinautoinjektormodelle auf dem deutschen Markt, die eine ausreichende Breite an Charakteristika aufweisen, um den meisten Patienten gerecht zu werden. Im vorliegenden Beitrag werden Indikationskriterien fur die Verschreibung vorgestellt, die Zahl der zu verschreibenden Autoinjektoren diskutiert, die richtige Injektionstechnik erlautert, Indikation zum Einsatz genannt und praktische Details erortert.

Die IgE-vermittelte Soforttypreaktion ist die haufigste Form der Nahrungsmittelallergie im Kindesalter. Es werden hierbei primare (vorwiegend fruhkindliche) und sekundare (vorwiegend pollenassoziierte) Allergien, die in ihrer Schwere unterschiedlich verlaufen, unterschieden. Huhnerei, Kuhmilch und Erdnuss sind hierbei haufige Ausloser der primaren Nahrungsmittelallergie. Wahrend die Huhnerei- und Kuhmilchallergie eine gute Prognose haben, bleibt die Erdnussallergie haufig lebenslang bestehen. Fur die Diagnostik sind die Anamnese, der Nachweis einer Sensibilisierung und ggf. eine orale Nahrungsmittelprovokation notwendig. Insbesondere bei der Erdnuss- und Haselnussallergie hat sich die komponentenbasierte Diagnostik, bei der spezifisches IgE gegen einzelne Allergene (z. B. Ara h 2) gemessen wird, als hilfreich erwiesen. In Bezug auf die Therapie ist die Eliminationsdiat nach wie vor das einzige anerkannte Verfahren. Die Beratung durch eine Ernahrungsfachkraft ist hierbei hilfreich. Patienten mit erhohtem Anaphylaxierisiko benotigen ein entsprechendes Notfallset, inklusive eines Adrenalinautoinjektors. Eine Instruktion im Umgang mit dem Autoinjektor sollte bei Verordnung erfolgen und ein Anaphylaxie-Pass ausgestellt werden. Des Weiteren ist die Teilnahme der Patienten bzw. ihrer Betreuer an einem Anaphylaxie-Schulungskurs zu empfehlen. Kausale Therapien wie die orale, sublinguale oder epikutane Immuntherapie sind zurzeit in der Entwicklung. In Bezug auf die Pravention der Nahrungsmittelallergie konnte gezeigt werden, dass es fur einen praventiven Effekt einer diatetischen Restriktion durch Meidung potenter Nahrungsmittelallergene im ersten Lebensjahr keine Belege gibt. Inwieweit jedoch die fruhzeitige Gabe praventiv und sicher ist, wird gerade in grosen kontrollierten Interventionsstudien untersucht. Es konnte kurzlich gezeigt werden, dass die Entwicklung einer Erdnussallergie in Sauglingen mit schwerer atopischer Dermatitis und/oder Huhnereiallergie in einem Land mit hoher Pravalenz durch die fruhzeitige Gabe im 4.–11. Lebensmonat verringert werden konnte, wenn die Kinder nicht bereits allergisch waren.

A recent genome-wide association study suggested novel candidate loci for food allergy. Apart from the established locus at 11q13, these revealed no association with food allergy in the Genetics Of Food Allergy Study.

Background Wheat is one of the most common food allergens in early childhood. In contrast to other food allergies, wheat-specific IgE correlates badly with clinical symptoms and relevant components have been identified mostly for wheat-depended exercise-induced anaphylaxis. Moreover, a high percentage of patients present with immediate type symptoms but wheat-specific IgE cannot be detected with commercial available systems. Objective We addressed the question whether the IgE recognition pattern between wheat allergic (WA) and clinically tolerant (WT) children differs in order to identify individual proteins useful for component-resolved diagnostics. Methods Sera of 106 children with suspected wheat allergy, of whom 44 children had clinical relevant wheat allergy and 62 were tolerant upon oral food challenge, were analyzed for wheat-specific IgE using the ImmunoCap system as well as immunoblots against water and salt soluble, and water-insoluble protein fractions. 40 randomly selected sera were analyzed for specific IgE to ω5-gliadin. Results Sixty-three percent of the WT and 86% of the WA children were sensitized to wheat with >0.35 kUA/l in ImmunoCAP analysis. We could confirm the role of α-, s-, γ-, and ω-gliadins, and LMW glutenin subunits as major allergens and found also IgE binding to a broad spectrum of water- and salt-soluble protein bands. It is of great importance that wheat allergic and tolerant patients showed IgE binding to the same protein bands. WT and WA did not significantly differ in levels of ω5-gliadin-specific IgE. Conclusions & Clinical Relevance Children with challenge proven clinical relevant food allergy and tolerant ones had a similar spectrum of IgE binding to the same protein bands. These findings imply that component-resolved diagnostics might not be helpful in the diagnostic work-up of wheat allergy.

S2k-Leitlinie der Deutschen Gesellschaft fur Allergologie und klinische Immunologie (DGAKI) in Zusammenarbeit mit dem Arzteverband Deutscher Allergologen (AeDA), dem Berufsverband der Kinder- und Jugendarzte (BVKJ), dem Deutschen Allergie- und Asthmabund (DAAB), der Deutschen Dermatologischen Gesellschaft (DDG), der Deutschen Gesellschaft fur Ernahrung (DGE), der Deutschen Gesellschaft fur Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS), der Deutschen Gesellschaft fur Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie, der Deutschen Gesellschaft fur Kinder- und Jugendmedizin (DGKJ), der Gesellschaft fur Padiatrische Allergologie und Umweltmedizin (GPA), der Deutschen Gesellschaft fur Pneumologie und Beatmungsmedizin (DGP), der Deutschen Gesellschaft fur Gastroenterologie und Ernahrung (GPGE), der Deutschen KontaktallergieGruppe (DKG), der Osterreichischen Gesellschaft fur Allergologie und Immunologie (OGAI), dem BerufsVerband Oecotrophologie e.V. (VDOE) und der Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF)

Dysfunktionelle respiratorische Symptome sind durch rekurrierend oder chronisch auftretende respiratorische Krankheitszeichen charakterisiert. Diese lassen sich nicht durch strukturelle Besonderheiten der Atemwege erklaren und konnen Symptome somatischer Erkrankungen imitieren (somatoforme Atemstorungen). Die fruhzeitige Diagnosestellung ist erforderlich, um die Entwicklung von Fehlanpassungen zu vermeiden. Mindestkriterien stehen zur Abgrenzung von somatischen Erkrankungen und fur die korrekte Diagnosestellung zur Verfugung. Therapeutische Strategien schliesen je nach Krankheitsbild Aufklarung uber die Gutartigkeit der Erkrankung, Training von physiologischer Atemtechnik, Selbstkontrolltechniken zur Vermeidung unphysiologischer respiratorischer Symptome und psychologische bzw. psychotherapeutische Unterstutzung ein. Untersuchungen zur Effizienz therapeutischer Strategien sind erforderlich.

Background Currently, there is no mandatory labelling of allergens for non-pre-packed foods in the EU. Therefore, consumers with food allergy rely on voluntary information provided by the staff. The aim of this study was to characterize allergic reactions to non-pre-packed foods and to investigate whether staff in bakery shops were able to give advice regarding a safe product choice. Methods Questionnaires were sent to 200 parents of children with a food allergy. Staff of 50 bakery shops were interviewed regarding selling non-pre-packed foods to food-allergic customers. Bakery products being recommended as ‘cow's milk-free’ were bought, and cow's milk protein levels were measured using ELISA. Results A total of 104 of 200 questionnaires were returned. 25% of the children experienced an allergic reaction due to a non-pre-packed food from bakery shops and 20% from ice cream parlours. Sixty percent of the bakery staff reported serving food-allergic customers at least once a month, 24% once a week. Eighty four percent of the staff felt able to advise food-allergic consumers regarding a safe product choice. Seventy three ‘cow's milk-free’ products were sold in 44 bakery shops. Cow's milk could be detected in 43% of the bakery products, 21% contained >3 mg cow's milk protein per serving. Conclusion Staff in bakery shops felt confident about advising customers with food allergy. However, cow's milk was detectable in almost half of bakery products being sold as ‘cow's milk-free’. Every fifth product contained quantities of cow's milk exceeding an amount where approximately 10% of cow's milk-allergic children will show clinical relevant symptoms.

The gold standard in the diagnostics of food allergy is oral food challenges (OFCs) - best performed in a double-blind, placebo-controlled manner (DBPCFC) [1]. Great efforts have been made to standardize oral food challenges [2]. As recommended, in our clinic oral food challenges are performed with semi-log dose increments every 30 minutes [3]. This article is protected by copyright. All rights reserved.

ZusammenfassungDysfunktionelle respiratorische Symptome sind durch rekurrierend oder chronisch auftretende respiratorische Krankheitszeichen charakterisiert, die sich nicht durch strukturelle Besonderheiten der Atemwege erklären lassen und Symptome somatischer Erkrankungen imitieren können (somatoforme Atemstörungen). Die Systematisierung von dysfunktionellen respiratorischen Symptomen sowie die Entwicklung diagnostischer und therapeutischer Algorithmen sind relativ junge Arbeitsfelder der Pädiatrischen Pneumologie. Inzwischen sind diagnostische Mindestkriterien vorgeschlagen worden, die zur besseren Erkennung und Abgrenzung von somatischen Erkrankungen beitragen sollen. Eine frühzeitige Diagnosestellung ist erforderlich, um der Entwicklung von Fehlanpassungen entgegenzuwirken.

Adverse food reactions are far more often perceived than objectively verified. In our scientific knowledge on non-allergic adverse reactions including the so called histamine intolerance, there are large deficits. Due to the fact that this disorder is increasingly discussed in the media and the internet, more and more people suspect it to be the trigger of their symptoms. The scientific evidence to support the postulated link between ingestion of histamine and adverse reactions is limited, and a reliable laboratory test for objective diagnosis is lacking. This position paper by the "Food Allergy" Working Group of the German Society for Allergology and Clinical Immunology (DGAKI) in collaboration with the German Association of Allergologists (AeDA), the Society for Pediatric Allergology and Environmental Medicine (GPA), and the Swiss Society for Allergology and Immunology (SGAI) reviews the data on the clinical picture of adverse reactions to ingested histamine, summarizes important aspects and their consequences, and proposes a practical diagnostic and therapeutic approach.

Elicitors of anaphylactic reactions are any sources of protein with allergenic capacity. However, not all allergic reactions end up in the most severe form of anaphylaxis. Augmenting factors may explain why certain conditions lead to anaphylaxis. Augmenting factors may exhibit three effects: lowering the threshold, increasing the severity, and reversing acquired clinical tolerance. Common augmenting factors are physical exercise, menstruation, NSAIDs, alcohol, body temperature, acute infections, and antacids. Therapeutic options may address causative, preventive, pragmatic, or symptomatic considerations: avoid the eliciting food, take an antihistamine before any situation with a possible risk of augmentation, separate food and sport (at least for 2 h), and carry an adrenaline autoinjector at all times. Individual patterns include summation effects and specific patterns. In conclusion, in the case of a suggestive history but a negative oral challenge, one should consider the possible involvement of augmenting factors; after anaphylactic reactions, always ask for possible augmentation and other risk factors during the recent past; if augmentation is suspected, oral food challenges should be performed in combination with augmenting factors; and in the future, standardized challenge protocols including augmenting factors should be established.

SummaryBackground The gold standard in the diagnosis of food allergy is the double-blind, placebo-controlled oral food challenge (DBPCFC). During this challenge, patients receive the allergenic food and placebo on separate randomized days, while being monitored for clinical reactions. Interestingly, some reactions are assessed as positive although the patients had received placebo. The aim of our study was to analyze incidence and characteristics of positive placebo reactions during DBPCFCs. Methods In food-allergic children, we retrospectively analyzed positive placebo reactions in DBPCFCs in 740 placebo challenges in our department. Individual characteristics were compared, such as age or IgE levels, as well as clinical symptoms. Results Of all placebo challenges, 2.8% (21 of 740) were assessed as positive. Young children (age ≤ 1.5 years) had more (P = 0.047) positive placebo challenges (4.0%) compared to older children (age > 1.5 years; 1.5%). Children with positive placebo challenges had higher levels of total IgE (median 201 kU/L) compared to negatively classified children (median 110 kU/L). In children with positive placebo reactions, skin symptoms were observed significantly more often, with a worsening of atopic eczema (AE) as the most reported symptom. Conclusion Placebo reactions in DBPCFC are not common. Worsening of AE is the most frequent clinical reaction associated with positive placebo challenges, and young children (age ≤ 1.5 years) seem to be affected more often. Therefore – contrary to current recommendations – DBPCFC tests should be considered in infants and young children, especially those with a history of AE.

A large proportion of immunoglobulin E (IgE)-mediated food allergies in older children, adolescents and adults are caused by cross-reactive allergenic structures. Primary sensitization is most commonly to inhalant allergens (e.g. Bet v 1, the major birch pollen allergen). IgE can be activated by various cross-reactive allergens and lead to a variety of clinical manifestations. In general, local and mild — in rare cases also severe and systemic — reactions occur directly after consumption of the food containing the cross-reactive allergen (e. g. plant-derived foods containing proteins of the Bet v 1 family). In clinical practice, sensitization to the primary responsible inhalant and/or food allergen can be detected by skin prick tests and/or in vitro detection of specific IgE. Component-based diagnostic methods can support clinical diagnosis. For individual allergens, these methods may be helpful to estimate the risk of systemic reactions. Confirmation of sensitization by oral provocation testing is important particulary in the case of unclear case history. New, as yet unrecognized allergens can also cause cross-reactions. The therapeutic potential of specific immunotherapy (SIT) with inhalant allergens and their effect on pollen-associated food allergies is currently unclear: results vary and placebo-controlled trials will be necessary in the future. Pollen allergies are very common. Altogether allergic sensitization to pollen and cross-reactive food allergens are very common in our latitudes. The actual relevance has to be assessed on an individual basis using the clinical information. Cite this as Worm M, Jappe U, Kleine-Tebbe J, Schafer C, Reese I, Saloga J, Treudler R, Zuberbier T, Wassmann A, Fuchs T, Dolle S, Raithel M, Ballmer-Weber B, Niggemann B, Werfel T. Food allergies resulting from immunological cross-reactivity with inhalant allergens. Allergo J Int 2014; 23: 1–16 DOI 10.1007/s40629-014-0004-6

To establish the effectiveness of interventions for the acute and long-term management of anaphylaxis, seven databases were searched for systematic reviews, randomized controlled trials, quasi-randomized controlled trials, controlled clinical trials, controlled before-after studies and interrupted time series and - only in relation to adrenaline - case series investigating the effectiveness of interventions in managing anaphylaxis. Fifty-five studies satisfied the inclusion criteria. We found no robust studies investigating the effectiveness of adrenaline (epinephrine), H1-antihistamines, systemic glucocorticosteroids or methylxanthines to manage anaphylaxis. There was evidence regarding the optimum route, site and dose of administration of adrenaline from trials studying people with a history of anaphylaxis. This suggested that administration of intramuscular adrenaline into the middle of vastus lateralis muscle is the optimum treatment. Furthermore, fatality register studies have suggested that a failure or delay in administration of adrenaline may increase the risk of death. The main long-term management interventions studied were anaphylaxis management plans and allergen-specific immunotherapy. Management plans may reduce the risk of further reactions, but these studies were at high risk of bias. Venom immunotherapy may reduce the incidence of systemic reactions in those with a history of venom-triggered anaphylaxis.

Bei alteren Kindern, Jugendlichen und Erwachsenen wird ein groser Teil Immunglobulin-E(IgE)-vermittelter Nahrungsmittelallergien durch kreuzreaktive allergene Strukturen ausgelost. Die primare Sensibilisierung ist vorrangig gegen Inhalationsallergene gerichtet (z. B. Bet v 1 als Hauptallergen der Birkenpollen). IgE kann uber verschiedene kreuzreaktive Allergene aktiviert werden und zu unterschiedlichen klinischen Manifestationen fuhren. In der Regel treten lokale und milde, selten auch schwere systemische Reaktionen direkt nach Verzehr des Nahrungsmittels auf, welches das kreuzreaktive Allergen enthalt (z. B. pflanzliche Nahrungsmittel mit Proteinanteil aus der Bet-v-1-Familie). In der klinischen Praxis konnen Sensibilisierungen gegen die primar verantwortlichen Inhalations- und/oder Nahrungsmittelallergene mit dem Pricktest und/oder der Bestimmung von spezifischem IgE in vitro erfasst werden. Die komponentenbasierte Diagnostik kann die klinische Diagnostik unterstutzen. Fur einzelne Allergene ermoglicht sie eine Risikoabschatzung fur das Auftreten systemischer Reaktionen. Sensibilisierungen mussen insbesondere bei unklarer Anamnese durch orale Provokationstests bestatigt werden. Auch neue, bisher unerkannte Allergene konnen Kreuzreaktionen hervorrufen. Das therapeutische Potenzial der spezifischen Immuntherapie mit inhalativen Allergenen und deren Wirkung auf die pollenassoziierte Nahrungsmittelallergie ist im klinischen Alltag variabel und letztlich nicht geklart. Placebokontrollierte Studien sind zukunftig erforderlich. Insgesamt treten allergische Sensibilisierungen gegen Pollen- und kreuzreaktive Nahrungsmittelallergene in unseren Breiten sehr haufig auf. Ihre aktuelle Relevanz ist mit Hilfe der klinischen Angaben individuell zu ermitteln.

Typische dysfunktionelle respiratorische Erkrankungen sind habitueller Husten, Seufzer-Dyspnoe, das Hyperventilationssyndrom, der dysfunktionelle Verschluss der Stimmbander wahrend der Inspiration („vocal cord dysfunction“) und primar psychogene Atemstorungen. Die Diagnosestellung sollte aufgrund der Symptome anhand positiver Kriterien erfolgen. Sorgfaltig muss von moglicherweise koexistierender somatischer Erkrankung abgegrenzt werden.

Reported food-related symptoms of patients may sometimes be misleading. A correct delineation of food-induced symptoms is often difficult and various differential diagnoses have to be considered. We report on two cases of food-induced, predominantly respiratory symptoms (in one case life-threatening) in children with food allergy. First, a two-year-old boy with no history of allergies and suspected foreign body aspiration which was finally diagnosed as an anaphylactic reaction to fish, and secondly a six-year-old girl with multiple food allergies and allergic asthma who during an electively performed oral food challenge developed severe respiratory distress, drop in blood pressure, and asphyxia not due to an anaphylactic reaction but due to choking on an unnoticed sweet. These two cases represent challenging, life-threatening symptom constellations involving food-induced reactions in food allergic children, reminding us to question first impressions.

Dysfunktionelle respiratorische Symptome konnen leicht ubersehen werden. Sie sind durch rekurrierend oder chronisch auftretende respiratorische Krankheitszeichen charakterisiert, die sich nicht durch strukturelle Besonderheiten der Atemwege erklaren lassen und Symptome somatischer Erkrankungen imitieren konnen (somatoforme Atemstorungen). Typische dysfunktionelle respiratorische Symptome sind habitueller Husten, Seufzer-Dyspnoe, das Hyperventilationssyndrom, der dysfunktionelle Verschluss der Stimmbander wahrend der Inspiration („vocal cord dysfunction“), und primar psychogene Atemstorungen. Die Diagnosestellung sollte aufgrund der Symptome anhand positiver Kriterien erfolgen. Sorgfaltig muss von moglicherweise koexistierender somatischer Erkrankung abgegrenzt werden. Die Therapie sollte ohne Verzug und ggf. interdisziplinar erfolgen, um der Entwicklung von Fehlanpassungen entgegenzuwirken und der Mehrdimensionalitat des Krankheitsbilds gerecht zu werden.

Background Studies about children with respiratory diseases in Africa are impeded by the dearth of reliable data for the vast majority of countries on the continent. This study was conducted to establish representative reference values, therefore allowing a more accurate evaluation of lung function in Malagasy children. Methods One thousand two hundred thirty-six students from three public and five private schools aged 8–12 years were recruited. A total of 1,093 children were healthy, had a valid lung function measurement and were thus deemed evaluable for this study. Lung function data were collected on consecutive days in Antananarivo, Madagascar's capital, using spirometry and a modified International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Results The lung volumes found were substantially lower compared to Caucasian and African equations. The mean Z-score (Stanojevic) for the forced vital capacity (FVC) found was −1.45 and −0.93 for the forced expiratory volume in 1 sec (FEV1) with significant differences between private and public schools (FVC: P = 0.0023, FEV1: P = 0.0004). Conclusions The equations established for school children in Madagascar's capital Antananarivo showed lung function values were lower than reference values for the same age group seen not only in European, but also in African American and African children. The unique ethnicity of the Malagasy people, which combines Southeast-Asian with substantial African influences, the heavy burden of pollution and poverty may explain these differences. Pediatr Pulmonol. 2014; 49:76–83. © 2013 Wiley Periodicals, Inc.

Background Although most of cow's milk (CM) allergic children will outgrow their allergy, the pathomechanism of the natural development of tolerance remains poorly understood. It has been suggested that the balance between milk-specific IgE and IgG4 plays a major role. Objective We aimed to investigate differences in IgE and IgG4 antibody binding to CM epitopes between patients with persistent CM allergy (CMA) and those that naturally became tolerant. Methods Sera from 35 children with proven CMA (median age at inclusion of 10 months) were analyzed retrospectively; 22 patients have become tolerant (median age at tolerance acquisition of 51 months) during the study period as confirmed by a negative oral food challenge. IgE and IgG4 binding to sequential epitopes derived from five major CM proteins were measured with a peptide microarray-based immunoassay. Results At baselines, greater intensity and broader diversity of IgE and IgG4 binding have been found in children with persistent CMA beyond 5 years of age compared to patients with transient CMA. Moreover, children with transient CMA had IgE and IgG4 antibodies that more often recognized the same epitopes, compared to those with persistent CMA. From baseline to the time of tolerance development, both IgE and IgG4 binding intensity decreased significantly, particularly in areas of α-s- and β-casein (P

Background The conduct of oral food challenges as the preferred diagnostic standard for food allergy was harmonized over the last years. However, documentation and interpretation of challenge results, particularly in research settings, are not sufficiently standardized to allow valid comparisons between studies. Our aim was to develop a diagnostic toolbox to capture and report clinical observations in double-blind placebo-controlled food challenges (DBPCFC). Methods A group of experienced allergists, paediatricians, dieticians, epidemiologists and data managers developed generic case report forms and standard operating procedures for DBPCFCs, and piloted them in three clinical centres. The follow-up of the EuroPrevall/iFAAM birth cohort and other iFAAM work packages currently apply these methods. Recommendations A set of newly developed questionnaire or interview items capture the history of food allergy. Together with sensitization status, this forms the basis for the decision to perform a DBPCFC, following a standardized decision algorithm. A generic form including details about severity and timing captures signs and symptoms observed during or after the procedures. In contrast to the commonly used dichotomous outcome food allergy versus no food allergy, the allergy status is interpreted in multiple categories to reflect the complexity of clinical decision making. Conclusion The proposed toolbox sets a standard for improved documentation and harmonized interpretation of DBPCFCs. By a detailed documentation and common terminology for communicating outcomes, these tools hope to reduce the influence of subjective judgment of supervising physicians. All forms are publicly available for further evolution and free use in clinical and research settings. This article is protected by copyright. All rights reserved.

Introduction Component-resolved diagnostics using specific IgE to 2 S albumins has shown to be a valuable new option in diagnostic procedure. Ana o 3 is a 2 S albumin from cashew. The aim of this study was to investigate the role of Ana o 3-specific serum IgE in the diagnosis of cashew allergy and to identify cut-off levels to replace oral food challenges. Moreover, the value of additional determination of total IgE has been investigated. Methods In a multicentre study, we analysed specific IgE to cashew extract and Ana o 3 as well as total IgE in children with suspected cashew allergy using the ImmunoCAP-FEIA and a standardized diagnostic procedure including oral challenges where indicated. Results A total of 61 patients were included in the study. Forty-two were allergic to cashew, and 19 were tolerant. In receiver operating curves, Ana o 3 discriminates between allergic and tolerant children better than cashew-specific IgE with an area under the curve of 0.94 vs 0.78. The ratio of Ana o 3-specific IgE to total IgE did not further improve the diagnostic procedure. Probability curves for Ana o 3-specific IgE have been calculated, and a 95% probability could be estimated at 2.0 kU/l. Conclusion Specific IgE to Ana o 3 is a valuable tool for the diagnosis of cashew allergy. Considering its positive predictive value, it might allow to make a considerable number of oral challenges superfluous.

IgE-mediated immediate type reactions are the most common form of food allergy in childhood. Primary (often in early childhood) and secondary (often pollen-associated) allergies can be distinguished by their level of severity. Hen's egg, cow's milk and peanut are the most common elicitors of primary food allergy. Tolerance development in hen's egg and cow's milk allergy happens frequently whereas peanut allergy tends toward a lifelong disease. For the diagnostic patient history, detection of sensitization and (in many cases) oral food challenges are necessary. Especially in peanut and hazelnut allergy component-resolves diagnostic (measurement of specific IgE to individual allergens, e. g. Ara h 2) seem to be helpful. In regard to therapy elimination diet is still the only approved approach. Patient education through dieticians is extremely helpful in this regard. Patients at risk for anaphylactic reactions need to carry emergency medications including an adrenaline auto-injector. Instruction on the usage of the adrenaline auto-injector should take place and a written management plan handed to the patient. Moreover, patients or caregivers should be encouraged to attending a structured educational intervention on knowledge and emergency management. In parallel, causal therapeutic options such as oral, sublingual or epicutaneous immunotherapies are currently under development. In regard to prevention of food allergy current guidelines no longer advise to avoid highly allergenic foods. Current intervention studies are investigating wether early introduction of highly allergic foods is effective and safe to prevent food allergy. It was recently shown that peanut introduction between 4 and 11 months of age in infants with severe atopic dermatitis and/or hen's egg allergy (if they are not already peanut allergic) prevents peanut allergy in a country with high prevalence.

BACKGROUND: Atopic dermatitis (AD) and food allergy frequently coexist in children.OBJECTIVE: To examine the association between food allergy and AD.METHODS: Between 2001 and 2011, children referred to our tertiary care center underwent double-blind, placebo-controlled food challenges (DBPCFCs) for one or more suspected food allergies as part of regular care. Immediate reactions were observed and recorded by allergy nursing staff, whereas late reactions were ascertained by semistructured telephone interview 48 hours after challenge. To test to which degree specific IgE results were predictive in the outcome of DBPCFCs in children with and without (previous and current) AD, logistic regression analysis was performed.RESULTS: A total of 1186 DBPCFCs were studied. Sensitization to foods occurred significantly more often in children with previous AD. The association between specific IgE results and the outcome of DBPCFCs was significant for children with and without (previous and current) AD but stronger for children without current AD. The positivity rate of DBPCFCs in children with mild, moderate, and severe AD was 53.3%, 51.7%, and 100%, respectively. Children with AD and a history of worsening AD as their only symptom reacted as often to placebo as to challenge food.CONCLUSION: Children with current AD are more frequently asymptomatically sensitized to the foods in question than those without AD. In addition, children suspected of food allergy should be considered for testing, regardless of the severity of their AD. Our results suggest that children with exacerbation of AD in the absence of other allergic symptoms are unlikely to be food allergic.

SummaryBackground Cow's milk allergy (CMA) is one of the most common causes of food allergy in the first years of life. Fortunately, the majority of children with CMA develop clinical tolerance with time. However, no good individual markers exist to predict whether this will occur. Therefore, a prognosis to identify children with persistent CMA at diagnosis would be helpful. Objective In this study, we sought to assess whether measurement of IgE to individual allergens of cow's milk (CM) would separate patients with persistent CMA from those who became clinically tolerant to CM over time. Methods A total of 52 patients ranging from 3 months to 114 months of age with proven CMA by DBPCFC were followed over time. From these 52 patients, 32 (61.5%) patients became tolerant in the analysed time period. All patients were rechallenged at least once, some were rechallenged two or three times. Serum was analysed prior to each challenge for specific IgE, IgG and IgG4 binding to crude CM protein as well as to individual allergens of CM. Results The individual likelihood of outgrowing CMA significantly correlates with a low level of CM-specific IgE as well as a low level of specific IgE to α-lactalbumin, β-lactoglobulin (Bos d5.0102), κ-casein and αs1-casein. No significant correlation was found for IgE levels to total casein, lactoferrin, β-casein and β-lactoglobulin (Bos d5.0101) as well as IgG and IgG4 levels to α-lactalbumin, β-lactoglobulin and total casein. Conclusions CM-specific IgE is a good prognostic marker for persistence of CMA. In addition, component-resolved diagnostic showed similar results. However, in our view, the rising laboratory costs do not justify a measurement on a daily basis. Additional determination of specific IgG or IgG4 levels was not useful in predicting tolerance development in our study population.

This article is the result of consensus reached by a working group of clinical experts in paediatric allergology as well as representatives from an ethical committee and the European Medicine Agency (EMA). The manuscript covers clinical, scientific, regulatory and ethical perspectives on allergen-specific immunotherapy in childhood. Unmet needs are identified. To fill the gaps and to bridge the different points of view, recommendations are made to researchers, to scientific and patient organizations and to regulators and ethical committees. Working together for the benefit of the community is essential. The European Academy of Allergy and Clinical Immunology (EAACI) serves as the platform of such cooperation.