Imke Reese

Guidelines on the management of IgE-mediated food allergies

S2k-Guidelines of the German Society for Allergology and Clinical Immunology (DGAKI) in collaboration with the German Medical Association of Allergologists (AeDA), the German Professional Association of Pediatricians (BVKJ), the German Allergy and Asthma Association (DAAB), German Dermatological Society (DDG), the German Society for Nutrition (DGE), the German Society for Gastroenterology, Digestive and Metabolic Diseases (DGVS), the German Society for Oto-Rhino-Laryngology, Head and Neck Surgery, the German Society for Pediatric and Adolescent Medicine (DGKJ), the German Society for Pediatric Allergology and Environmental Medicine (GPA), the German Society for Pneumology (DGP), the German Society for Pediatric Gastroenterology and Nutrition (GPGE), German Contact Allergy Group (DKG), the Austrian Society for Allergology and Immunology (OGAI), German Professional Association of Nutritional Sciences (VDOE) and the Association of the Scienti‰c Medical Societies Germany (AWMF)

Approach to suspected food allergy in atopic dermatitis

The following guideline of the “Arbeitsgruppe Nahrungsmittelallergie der DGAKI” (Task Force on Food Allergy of the German Society of Allergology and Clinical Immunology) and the ÄDA (“Ärzteverband Deutscher Allergologen”, Medical Association of German Allergologists) and the GPA (German Society of Pediatric Allergology) summarizes the approach to be taken when food allergy is suspected in patients with atopic dermatitis (neurodermatitis, atopic eczema). The problem is clinically relevant because many patients assume that allergic reactions against foods are responsible for triggering or worsening their eczema. It is important to identify those patients who will benefit from an elimination diet but also to avoid unnecessary diets. Elimination diets (especially in early childhood) are associated with the risk of malnutrition and additional emotional stress for the patients. The gold standard for the diagnosis of food‐dependent reactions is to perform placebo‐controlled, double‐blind oral food challenges because specific IgE, prick tests and history often do not correlate with clinical reactivity. This is particularly true in the case of delayed eczematous skin reactions. Diagnostic elimination diets should be used before an oral provocation test. If multiple sensitizations against foods are discovered in a patient, an oligoallergenic diet and a subsequent stepwise supplementation of the nutrition should be performed. If a specific food is suspected of triggering food allergy, oral provocation should be performed after a diagnostic elimination diet. As eczema‐tous skin reactions may develop slowly (i. e. within one or two day), the skin be inspected the day after the provocation test and that a repetitive test be performed if the patient has not reacted to a given food on the first day of oral provocation. The guideline discusses various clinical situations for patients with atopic dermatitis to facilitate differentiated diagnostic procedures.

Food allergies resulting from immunological cross-reactivity with inhalant allergens

SummaryA 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, Schäfer C, Reese I, Saloga J, Treudler R, Zuberbier T, Wassmann A, Fuchs T, Dölle 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

Diagnostic approach for suspected pseudoallergic reaction to food ingredients

Chronic urticaria, recurrent angioedema and non‐allergic asthma have all been associated with pseudoallergic reactions to food ingredients. For atopic dermatitis and diseases of the gastrointestinal tract, this association is controversial. Pseudoallergic reactions can be elicited by additives as well as by natural food ingredients. An altered histamine metabolism may be associated with pseudoallergy.

S3-Guideline on allergy prevention: 2014 update

The continued high prevalence of allergic diseases in Western industrialized nations combined with the limited options for causal therapy make evidence-based primary prevention necessary. The recommendations last published in the S3-guideline on allergy prevention in 2009 have been revised and a consensus reached on the basis of an up-to-date systematic literature search.Evidence was sought for the period between May 2008 and May 2013 in the Cochrane and MEDLINE electronic databases, as well as in the reference lists of recent review articles. In addition, experts were surveyed for their opinions. The relevance of retrieved literature was checked by means of two filter processes: firstly according to title and abstract, and secondly based on the full text of the articles. Included studies were given an evidence grade, and a bias potential (low/high) was specified for study quality. A formal consensus on the revised recommendations was reached by representatives of the relevant specialist societies and (self-help) organizations (nominal group process).Of 3,284 hits, 165 studies (one meta-analysis, 15 systematic reviews, 31 randomized controlled trials, 65 cohort studies, 12 case-control studies and 41 cross-sectional studies) were included and evaluated. Recommendations on the following remain largely unaltered: full breastfeeding for 4 months as a means of allergy prevention (hypoallergenic infant formula in the case of infants at risk); avoidance of overweight; fish consumption (during pregnancy/lactation and in the introduction of solid foods for infants); vaccination according to the recommendations of the German Standing Committee on Vaccination (Ständige Impfkommission, STIKO); avoidance of air pollutants and tobacco exposure and avoidance of indoor conditions conducive to the development of mold. The assertion that a reduction in house-dust mite allergen content as a primary preventive measure is not recommended also remains unchanged. The introduction of solid foods into infant diet should not be delayed. In the case of children at risk cats should not be acquired as domestic pets. Keeping dogs is not associated with an increased risk of allergy. The updated guideline includes a new recommendation to consider the increased risk of asthma following delivery by cesarean section. Additional statements have been formulated on pre- and probiotic agents, psychosocial factors, medications, and various nutritional components.Revising the guideline by using an extensive evidence base has resulted not only in an endorsement of the existing recommendations, but also in modifications and in the addition of new recommendations. The updated guideline enables evidence-based and up-to-date recommendations to be made on allergy prevention.

Vorgehen bei vermuteter Nahrungsmittelallergie bei atopischer Dermatitis

Zusammenfassung In der vorliegenden Leitlinie der Arbeitsgruppe Nahrungsmittelallergie der DGAKI, des ÄDA und der GPA werden verschiedene Vorgehensweisen bei vermuteter Nahrungsmittelallergie bei atopischer Dermatitis (Neurodermitis, atopisches Ekzem) diskutiert. Das Problem ist klinisch relevant, da viele Patienten vermuten, dass allergische Reaktionen gegen Nahrungsmittel Ekzeme auslösen oder verschlechtern können. Die Kunst besteht darin, die Patienten, die tatsächlich von einer Eliminationsdiät profitieren, zu identifizieren und gleichzeitig zu verhindern, dass zu häufig unnötige Diäten mit der Gefahr der Fehlernährung und der zusätzlichen emotionalen Belastung durchgeführt werden. Als Goldstandard in der Diagnostik nahrungsmittelabhängiger Reaktionen gilt die plazebokontrollierte, doppelblinde orale Provokation, da spezifisches IgE, Prick-Tests und anamnestische Angaben häufig nicht mit der Klinik korrelieren. Dieses gilt insbesondere für verzögert einsetzende Ekzemreaktionen. Das Instrument der diagnostischen Elimi nationsdiät sollte vor einer oralen Provokation genutzt werden. Bei multiplen Sensibilisierungen besteht die Möglichkeit einer zeitlich befristeten oligoallergenen Basisdiät und an schließendem stufenweisen Kos taufbau. Bei gezieltem Verdacht auf eine Nahrungsmittelallergie sollte die orale Provokation nach ebenso gezielter Eliminationsdiät durchgeführt werden. Aufgrund der sich zum Teil langsam entwickelnden Ekzemverschlechterungen wird empfohlen, zumindest am Tag nach der Provokation dieser Haut zu untersuchen und ggf. eine repetitive Testung durchzuführen, wenn es am ersten Tag der oralen Provokation nicht zu einer klinischen Reaktion gekommen ist. In der Leitlinie werden verschiedene klinische Konstellationen diskutiert, die ein differenziertes Vorgehen bei Patienten mit atopischer Dermatitis ermöglichen. Summary The following guideline of the “Arbeitsgruppe Nahrungsmittelallergie der DGAKI” and the ÄDA (Task Force on Food Allergy of the German Society of Allergology and Clinical Immunology and the Ärzteverband Deutscher Allergologen) summarizes different procedures, when food allergy is suspected in atopic dermatitis (neurodermatitis, atopic eczema). The problem is clinically relevant because many patients assume allergic reactions against foods being responsible for triggering eczematous reactions or worsening eczema. It is important to identify such patients who indeed benefit from an elimination diet and to avoid unneccessary diets. Elimination diets (especially in early childhood) are associated with the risk of malnutrition and additional emotional stress for the patients. The gold standard for the diagnosis of food-dependent reactions is to perform placebo-controlled, double-blind oral food challenges because specific IgE, prick tests and anamnestic data often do not correlate with clinical reactivity. This is particularly true in the case of delayed eczematous skin Leitlinie

Therapiemöglichkeiten bei der IgE-vermittelten Nahrungsmittelallergie

ZusammenfassungNach eindeutigem Nachweis einer Nahrungsmittel-Allergie möglichst mittels doppelblind und plazebo-kontrolliert durchgeführter oraler Provokation stellt sich die Frage der therapeutischen Möglichkeiten. Die Karenz ist die einzige Intervention, deren Effekt geprüft ist. Der Patient muss ausführliche Diätpläne mit Meidungsstrategien und Hinweisen zu sinnvollem Ersatz der Ernährung erhalten und eingehend beraten werden. Die Karenz muss im Fall von Allergenen, die potenziell schwere anaphylaktische Reaktionen auslösen können, mit Notfall-Medikamenten (schnell absorbierbares orales Antihistaminikum, Glukokortikosteroid, Adrenalin) kombiniert werden. Eine Reexposition erscheint nur unter ärztlicher Aufsicht nach ein bis zwei Jahren gerechtfertigt. Die bei anderen allergischen Erkrankungen kausal wirkende Therapie der Hyposensibilisierung (spezifische Immuntherapie) stellt bei der Nahrungsmittel-Allergie die Ausnahme dar.Bei der baumpollenassoziierten Nahrungsmittel-Allergie kann den Patienten in Aussicht gestellt werden, dass sich nach Hyposensibilisierung mit einem Baumpollenextrakt auch die Reaktion auf die Nahrungsmittel bessert. Die subkutane Hyposensibilisierung mit Nahrungsmittelextrakten ist dagegen ausschließlich wissenschaftlichen Untersuchungen vorbehalten. Eine orale Toleranzinduktion mit nativen Nahrungsmitteln kommt nur in Einzelfällen und bei nicht sicher meidbaren Nahrungsmitteln infrage.Haben Patienten vorwiegend gastrointestinale Beschwerden, kann eine zeitlich begrenzte Therapie mit Cromoglykat versucht werden. Bei leichten Symptomen empfiehlt sich zur symptomorientierten Therapie ein modernes, nicht sedierendes, schnell wirksames Antihistaminikum.Abzulehnen sind „alternative Therapieformen“ wie Rotationskost oder so genannte „bioenergetische Verfahren“ wie Elektroakupunktur nach Voll oder Bioresonanz.SummaryOnce the diagnosis of food allergy is established by double-blind, placebo-controlled food challenges, the only proven therapy is a strict elimination diet. Special food exclusion diets exist that allow patients to avoid food allergens while maintaining a good quality of life. If the allergen provokes anaphylactic reactions, the restriction diet has to be combined with the prescription of an emergency medication (antihistamine, corticosteroid, adrenaline). As symptomatic food allergy is often „lost“ over time, food challenges can be repeated at intervals of one to two years under monitored conditions.Immunotherapy with food extracts should only be used in controlled studies for the treatment of food hypersensitivity. Concerning their associated food allergy, patients with tree pollen allergy may profit from a specific immunotherapy with tree pollen extract. An induction of oral tolerance using increasing amounts of raw food is only useful in selected, highly compliant patients and in instances of not reliably avoidable foods. Antihistamines may partially mask symptoms of oral allergy syndrome and IgE-mediated skin symptoms.In allergic reactions with gastrointestinal disorders, Cromoglycate might be used for a short time. Alternative therapies such as rotation diets, electroacupuncture, or bioresonance should be disapproved.

Skin testing with food allergens

Skin testing has a central role in the diagnosis of food allergy. Prick testing is well‐ established as a routine diagnostic tool. Nonetheless, unstable allergens and the lack of standardized extracts create difficulties in the identification of sensitization to foods in patients with suspected food allergy. Therefore prick‐to‐prick tests with native (raw, fresh) foods are still recommended. The indications and contraindications are the same as those of routine skin testing in clinical allergology. We recommend a careful and restricted application of skin tests in patients with a history of severe anaphylaxis to foods.

Nahrungsmittelallergien durch immunologische Kreuzreaktionen

ZusammenfassungGrundlage für die Mehrzahl IgE-vermittelter Nah rungsmittelallergien im Erwachsenenalter sind kreuzreagierende Allergene. Ähnliche Molekül strukturen in Inhalations- und Nahrungsmittelallergenen bedingen die Bildung kreuzreagierender IgE-Antikörper. Damit wird infolge der Sensibilisierung gegen ein Kreuzallergen, meist primär ein Inhalationsallergen, ein ganzes Spektrum an Sensibilisierungen ausgelöst, und bereits der Erstkontakt mit dem Nahrungsmittel kann eine anaphylaktische Reaktion provozieren. Die größte Bedeutung haben pollenassoziierte Nahrungsmittelallergien, wobei die baumpollenassoziierten Allergien am besten untersucht sind.Für die klinische Praxis reicht es nicht aus, mit tels immunologischer Tests eine Kreuzreaktion nach zuweisen, sondern es muss zwischen einer Sensibilisierung ohne klinische Relevanz und einer klinischen Manifestation der Allergie unterschieden werden, weswegen bei unklarer Anamnese die Durchführung oraler Provokationstests notwendig wird.Dass baumpollenassoziierte Nahrungsmittelall ergien durch die spezifische Immuntherapie mit Baumpollen eine Besserung erfahren können, zeigen einige offene Studien an Baumpollenallergikern. Wenigstens 50% dieser Patienten mit zusätzlichen Symptomen auf Nahrungsmittel beobachteten un ter der Immuntherapie neben einer Besserung der polleninduzierten Beschwerden auch einen positi ven Einfluss auf die Nahrungsmittelallergie. Aller dings stehen plazebokontrollierte Studien aus.Angesichts der Zunahme der Pollenallergien, der Verschiebung des Sensibilisierungsspektrums und einer Änderung unserer Essgewohnheiten muss mit neuen, bisher unbekannten Kreuzreakti onen gerechnet werden.SummaryIn adults, the majority of IgE-mediated food aller gies is caused by cross-reacting allergen molecular structures that are present in inhalant as well as food allergens. On the one hand, synthesis of IgE stimulated by a cross-reactive allergen in pollen can result in a diverse pattern of sensitizations against various foods. On the other hand, even anaphylactic reactions may occur after first consumption of a food containing a cross-reactive allergen.In clinical practice, it is not sufficient to detect cross-reactivities by immunologic assays. Clinically relevant sensitizations have to be distinguished from clinically irrelevant IgE responses. Hence, in cases of unclear history oral challenge tests are nec essary.A few open studies have demonstrated the therapeutic potential in pollen-related food allergy: in at least 50% of the cases, tree pollen immunotherapy led to an improvement of associated food allergies. However, these results have to be con firmed in placebo-controlled studies.As we are facing an increase of pollen allergies, a shift in sensitization patterns and changes in nutri tional habits, the occurrence of new, so far unknown cross-reactions is expected.

Skin testing with food allergens. Guideline of the German Society of Allergology and Clinical Immunology (DGAKI), the Physicians' Association of German Allergologists (ADA) and the Society of Pediatric Allergology (GPA) together with the Swiss Society of Allergology.

Skin testing has a central role in the diagnosis of food allergy. Prick testing is well‐ established as a routine diagnostic tool. Nonetheless, unstable allergens and the lack of standardized extracts create difficulties in the identification of sensitization to foods in patients with suspected food allergy. Therefore prick‐to‐prick tests with native (raw, fresh) foods are still recommended. The indications and contraindications are the same as those of routine skin testing in clinical allergology. We recommend a careful and restricted application of skin tests in patients with a history of severe anaphylaxis to foods.