Ute Lepp

Die spezifische Immuntherapie (Hyposensibilisierung) bei IgE-vermittelten allergischen Erkrankungen

The present guideline on allergen-specific immunotherapy (SIT) was established by the German allergy societies in conjunction with other scientific and medical societies (dermatology, ear-nose-throat, pediatrics, lung and airway diseases) and a patient support group according to criteria of the Association of the Scientific Medical Societies in Germany (AWMF). Subcutaneous immunotherapy (SCIT) is a unique causal treatment of IgE-mediated allergic diseases and induces longterm tolerance to the applied allergens due to numerous immunologic effects. Non-modified allergens are used as aqueous or physically coupled (depot) allergen extracts, chemically modified allergens (allergoids) are used as depot extracts for SCIT. Efficacy of SCIT has been demonstrated for pollen and house dust mite allergens in a large number of studies in patients with allergic rhinoconjunctivitis, and for animal dander (cat) and mold allergens (Alternaria, Cladosporium) in few studies. SCIT has been well-studied in intermittent and mild persisting IgE-mediated allergic asthma and is recommended as a therapeutic option besides allergen avoidance and pharmacotherapy. Preventive aspects, particularly reduced development of bronchial asthma and less novel allergic sensitizations, are increasingly considered during the decision for SCIT. In case of systemic reactions due to Hymenoptera (bee, wasp) venom allergy SCIT has excellent efficacy and should be continued for at least 3 - 5 years. An extended, sometimes lifelong SCIT, is necessary in a few patients. SCIT is indicated in patients with IgE-mediated sensitizations and corresponding clinical symptoms to allergens which do not permit allergen avoidance and which are available as suitable extracts. Diagnostic procedures, indication and selection of appropriate allergens for SCIT are made by a physician with certified training or qualified knowledge and skills in allergology. Contraindications have to be considered on an individual basis. Injections of SCIT are administered by a physician experienced in this therapy and who is able to perform emergency treatment in case of an allergic adverse event. Patients information and documentation are mandatory previous to the start of SCIT. Children tolerate SCIT very well and benefit especially from its immuno-modulatory effects. Systemic adverse reactions can occur due to SCIT, being rare in case of complete adherence to safety standards. Most adverse events are mild to moderate and easily treatable. Risk factors for and sequels of unwanted systemic effects can effectively be minimized by training the staff members involved, adhering to safety standards and immediate emergency treatment. Sublingual immunotherapy (SLIT) is an option for adults with allergic rhinoconjunctivitis due to pollen allergens, particularly if SCIT is not suitable. In house dust mite allergy and allergic asthma, SLIT does not substitute SCIT. Due to the present data, SLIT is not recommended for routine use in children and adolescents. A final conclusion on SLIT for children and adolescents is warranted if further study results are available. Various research fields like allergen characterization, routes of application, adjuvants, updosing regimen and preventive aspects demonstrate new developments in SIT being currently examined for clinical efficacy.

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.

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.

Anaphylactic reaction to lupine flour

Roasted lupine seeds have been used as snack food in Mediterranean countries for years. Since the 1990s, lupine flour has been used as a substitute for or additive to other flours in countries of the European Union; usually the amount is so low that no declaration is required. Since 1994, a number of cases of immediate‐type allergy to lupine flour‐containing products have been published. A 52‐year‐old woman developed facial and mucosal edema, followed by dizziness and shortness of breath a few minutes after ingestion of a nut croissant con‐taining lupine flour; she required emergency care. Allergy diagnostic tests revealed a total IgE of 116 kU/l, a highly elevated concentration of IgE specific for lupine seed (42.9 kU/l) and birch pollen IgE of 2.57 kU/l. Skin prick test with native lupine flour was strongly positive. Allergy against lupine seeds may develop de novo or via cross‐reactivity to legumes, particularly peanuts, the latter being detectable in up to 88% of cases, founded on a strong sequence similarity between lupine and peanut allergens. In our patient, no cross‐reactivity could be detected via immunoblotting, indicating a rare monovalent sensitization to lupine flour. Treatment consists of avoidance of lupine flour‐containing products. Patients with proven peanut allergy should also avoid lupine flour because of the major risk of cross‐reaction.

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.

Vorgehen bei Verdacht auf Unverträglichkeit gegenüber oral aufgenommenem Histamin Leitlinie der Deutschen Gesellschaft für Allergologie und klinische Immunologie (DGAKI), der Gesellschaft für Pädiatrische Allergologie und Umweltmedizin (GPA) und des Ärzteverbandes Deutscher Allergologen (ÄDA)

Nahrungsmittelunvertraglichkeiten sind deutlich seltener objektiv nachweisbar als subjektiv empfunden. Insbesondere zum wissenschaftlichen Kenntnisstand nichtallergischer Uberempfindlichkeitsreaktionen bestehen grose Defizite. Ein Beispiel ist die Histamin-unvertraglichkeit, die. aufgrund der starken Thematisierung in den Medien und im Internet von Betroffenen oftmals als Ausloser ihrer Gesundheitsbeschwerden vermutet wird. Die wissen-schaftliehe Evidenz fur die postulierten Zusammen-hange ist begrenzt, eine verlassliche Labarbestirnmung zur definitiven Diagnose nicht vorhanden. Obwohl wissen-schaftliche Untersuchungen zur Unvertraglichkeit gegenuber exogen zugefuhrtem Histamin bisher ausschlieslich bei Erwachsenen durchgefuhrt wurden, wird die Diagnose auch bei Kindern und Jugendlichen gestellt, mit oftmals ein-schneidenden Konsequenzen fur den Speiseplan der Betroffenen. Die vorliegende Leitlinie der Arbeitsgruppe Nahrungsmittelallergie der Deutschen Gesellschaft fur Allergologie und klinische Immunologie (DGAKI) in Zusammenarbeit mit dem Arzteverband Deutscher Allergologen (ADA) und der Gesellschaft fur Padiatrisehe Allergologie und Umweltmedizin (GPA) fasst wichtige Aspekte zur Histaminunvertraglichkeit und deren Konsequenzen fur die Diagnostik und Therapie zusammen.

German guideline for the management of adverse reactions to ingested histamine

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.