Torsten Zuberbier

EAACI/GA(2)LEN/EDF/WAO guideline: management of urticaria.

This guideline, together with its sister guideline on the classification of urticaria (Zuberbier T, Asero R, Bindslev‐Jensen C, Canonica GW, Church MK, Giménez‐Arnau AM et al. EAACI/GA²LEN/EDF/WAO Guideline: definition, classification and diagnosis of urticaria. Allergy 2009;64: 1417–1426), is the result of a consensus reached during a panel discussion at the Third International Consensus Meeting on Urticaria, Urticaria 2008, a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the EU‐funded network of excellence, the Global Allergy and Asthma European Network (GA²LEN), the European Dermatology Forum (EDF) and the World Allergy Organization (WAO). As members of the panel, the authors had prepared their suggestions regarding management of urticaria before the meeting. The draft of the guideline took into account all available evidence in the literature (including Medline and Embase searches and hand searches of abstracts at international allergy congresses in 2004–2008) and was based on the existing consensus reports of the first and the second symposia in 2000 and 2004. These suggestions were then discussed in detail among the panel members and with the over 200 international specialists of the meeting to achieve a consensus using a simple voting system where appropriate. Urticaria has a profound impact on the quality of life and effective treatment is, therefore, required. The recommended first line treatment is new generation, nonsedating H1‐antihistamines. If standard dosing is not effective, increasing the dosage up to four‐fold is recommended. For patients who do not respond to a four‐fold increase in dosage of nonsedating H1‐antihistamines, it is recommended that second‐line therapies should be added to the antihistamine treatment. In the choice of second‐line treatment, both their costs and risk/benefit profiles are most important to consider. Corticosteroids are not recommended for long‐term treatment due to their unavoidable severe adverse effects. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS).

GM-CSF downmodulates c-kit, FcεRIα and GM-CSF receptor expression as well as histamine and tryptase levels in cultured human mast cells

Abstract GM-CSF is known primarily as a hematopoietic growth factor, but it has also been shown to inhibit mast cell differentiation in vitro. In order elucidate the mechanisms involved, we investigated the effects of GM-CSF in vitro on the differentiation of human leukemic mast cells (HMC-1 cells) and normal cord blood-derived mast cells (CBMC) under the influence of SCF, NGF, and fibroblast supernatant (FS). Under all culture conditions, GM-CSF induced a dose- and time-dependent reduction in intracellular histamine levels, tryptase activity, and numbers of cells immunoreactive for c-Kit and FcÂRI·. This effect leveled off between 10–100 ng/ml and after 4 days of culture. There was an associated decrease in mRNA expression for c-kit, FcÂRI· and tryptase. In contrast, no significant changes in the expression of the NGF receptor TrkA were noted under the same conditions. The GM-CSF receptor was found in HMC-1 cells and CBMC at both the mRNA and protein levels, but its expression decreased during culture with FS, and even more markedly during culture with GM-CSF. GM-CSF thus selectively inhibits in vitro induction and/or upregulation of all major mast cell characteristics in HMC-1 cells and CBMC irrespective of the growth factors present, and a concomitant downregulation of GM-CSF receptors can counteract these effects. GM-CSF may therefore function as a regulatory factor in mast cell growth and differentiation under normal and pathological conditions.

European Symposium on Precision Medicine in Allergy and Airways Diseases: Report of the European Union Parliament Symposium (October 14, 2015)

The European Academy of Allergy and Clinical Immunology (EAACI), the European Rhinologic Society (ERS), and the European Medical Association (EMA) organized, on October 14, 2015, a symposium in the European Parliament in Brussels on Precision Medicine in Allergy and Airways Diseases, hosted by MEP David Borrelli, and with active participation of the EU Commissioner for Health and Food Safety Vytenis Andriukaitis, MEP Sirpa Pietikainen, Chair of the European Parliament Interest Group on Allergy and Asthma, the European Respiratory Society (ERS), the European Federations of Allergy and Airways Diseases Patients Associations (EFA), the Global Allergy and Asthma European Network (Ga2len), Allergic Rhinitis and Its Impact on Asthma (ARIA), and the Respiratory Effectiveness Group (REG). The socioeconomic impact of allergies and chronic airways diseases cannot be underestimated, as they represent the most frequently diagnosed chronic noncommunicable diseases in the EU; 30% of the total European population is suffering from allergies and asthma, and more than half are deprived from adequate diagnosis and treatment. Precision medicine represents a novel approach, embracing four key features: personalized care based on molecular, immunologic, and functional endotyping of the disease, with participation of the patient in the decision‐making process of therapeutic actions, and considering predictive and preventive aspects of the treatment. Implementation of precision medicine into clinical practice may help to achieve the arrest of the epidemic of allergies and chronic airways diseases. Participants underscored the need for optimal patient care in Europe, supporting joint action plans for disease prevention, patient empowerment, and cost‐effective treatment strategies.

Evaluation of systemic provocation tests in patients with suspected allergic and pseudoallergic drug reactions.

In order to examine the diagnostic value of systemic provocation tests, we studied 56 inpatients hospitalized for identification of the agent eliciting previous severe allergic or pseudoallergic reactions to non-steroidal anti-inflammatory drugs, local anaesthetics or antibiotics. Skin tests were positive in only 4 patients reacting to antibiotics and propyphenazone and were always negative for local anaesthetics (n = 32). Only 4 of 26 patients reacted to oral or subcutaneous provocation, 3 times to penicillin and once each to mepivacain, propyphenazone and cyanocobalamine when the suspected drug was tested. In the remaining 30 patients, who for safety reasons were tested only with alternative drugs, none had positive reactions, but 11 patients reported non-specific symptoms, as did 9 of 21 patients given placebo. Systemic provocation tests for drug allergy thus gave few positive results. However, these tests should always be done together with placebo testing for validation of results, and they remain indispensable for identification of alternative, well-tolerated drugs.

Allergy immunotherapy across the life cycle to promote active and healthy ageing

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

European symposium on precision medicine in allergy and airways diseases: report of the European Union parliament symposium (October 14, 2015)

On 14 October 2015, the European Academy of Allergy and Clinical Immunology (EAACI), the European Rhinologic Society (ERS) and the European Medical Association (EMA) organized a symposium in the European Parliament in Brussels on Precision Medicine in Allergy and Airways Diseases, hosted by MEP David Borrelli and with active participation of the European Respiratory Society (ERS), the European Federations of Allergy and Airways Diseases Patients Associations (EFA), the Global Allergy and Asthma European Network (Ga2len), Allergic Rhinitis and Its Impact on Asthma (ARIA) and the Respiratory Effectiveness Group (REG). MEP Sirpa Pietikainen, Chair of the European Parliament Interest Group on Allergy and Asthma, underlined the importance of the need for a better diagnostic and therapeutic approach for patients with Allergies and Chronic Airways Diseases, and encouraged a joint initiative to control the epidemic of Allergy and Asthma in Europe. The socio-economic impact of allergies and chronic airways diseases cannot be underestimated, as they represent the most frequently diagnosed chronic non-communicable diseases in the EU. Despite the fact that 30% of the total European population is nowadays suffering from allergies and asthma, more than half of these patients are deprived from adequate diagnosis and treatment. Precision Medicine represents a novel approach in medicine, embracing 4 key features: personalized care based on molecular, immunologic and functional endotyping of the disease, with participation of the patient in the decision making process of therapeutic actions, and taking into account predictive and preventive aspects of the treatment. Implementation of Precision Medicine into clinical practice may help to achieve the arrest of the Epidemic of Allergies and Chronic Airways Diseases. This report summarizes the key messages delivered during the symposium by the speakers, including the EU Commissioner for Health and Food Safety Vitenys Andriukaitis. The Commissioner underscored the need for optimal patient care in Europe, supporting joint action plans for disease prevention, patient empowerment and cost-effective treatment strategies leading to a better health status of European citizens.

S3-Leitlinie Urtikaria. Teil 2: Therapie der Urtikaria deutschsprachige Version der internationalen S3-Leitlinie

s internationaler Allergiekongresse von 2004 bis 2008). Die Leitlinie baut auf die Konsensusxad berichte des ersten und des zweiten Symposiums im Jahr 2000 und 2004 auf [184, 186]. Der Leitxad linienentwurf wurde von den Podiumsmitgliedern und den Teilnehmern im Auditorium im Detail besprochen, um, wo erforderlich, einen Konsens mittels eines einfachen Abstimmungssystems zu erzielen. Die Teilnahme von über 200 Urtikariaxad spezialisten aus 33 Ländern ermöglichte es, in diexad sen Konsens regionale Unterschiede europäischer und weltweiter Ansichten aufzunehmen und bietet eine Basis für eine verbesserte Vergleichbarkeit zuxad künftiger Studien auf dem Gebiet der Urtikaria. Während des internationalen Konsensustreffens vom 4. bis 5. Dezember 2008 in Berlin waren die deutschsprachigen Leitlinienautoren auf dem Podixad um oder im Auditorium vertreten. Während dieses Treffens fand auch eine erste Sitzung der Autoren zur Erstellung der deutschsprachigen Leitlinie statt, eine zweite Sitzung am 30. April 2009 während der DDGxadTagung in Dresden und ein drittes Treffen während der DGAKIxadTagung in Berlin am 3. Sepxad tember 2009. Diese Leitlinie orientiert sich an der internationalen [187] und wurde für den deutschxad sprachigen Raum angepasst. Die Leitlinienautoren haben festgestellt, dass prinzipiell keine Unterschiede in den Vorgehensweisen zwischen diesen Leitlinien bestehen. Urtikaria stellt eine heterogene Gruppe von Krankheiten dar, die eine Vielzahl von Ursachen haben, durch verschiedene Faktoren ausgelöst werxad den und sich klinisch auf sehr unterschiedliche Art und Weise präsentieren können (s. Schwesterleitlinie „Klassifikation und Diagnostik der Urtikaria“). Das panel discussion at the 3rd Inter national Consensus Meeting on Urticaria, “Urticaria 2008”. “Urticaria 2008” was a joint initiative of the Dermatology Section of the EAACI (European Academy of Allergy and Clinical Immunology), the EUxadfunded network of excellence GA2LEN (Global Allergy and Asthma Euroxad pean Network), the EDF (European Dermatology Forum) and the WAO (World Allergy Organization). The authors of the German language version joined the Consensus Meeting.

Gelatin-induced urticaria and anaphylaxis after tick-borne encephalitis vaccine.

Sir, Tick-borne encephalitis (TBE) is a rare disease, acquisition of which occurs only in well-known endemic areas, such as south-western Germany, Austria and Switzerland, through the bites of infected ticks. The course of the disease is not trivial: 0.5 ± 2% of cases are fatal, 2.7% have persistent serious paralysis and some 33% a postencephalitic syndrome. Since there is no speci®c treatment for TBE, immunoprophylaxis is used in endemic areas for controlling this disease. Active immunization has been shown to be effective and safe. Only a few mild side-effects have been reported (1). Allergic reactions to vaccines occur in approximately 0.001 ± 1% of cases (2) and most important antigens are preservatives, rarely antibiotics, culture media substances from the production process or reagents used for inactivation, stabilizers or absorbents (2). Allergic reactions to vaccines are localized mainly to the application site, whereas the onset of systemic anaphylaxis is extremely rare.

Effect of granulocyte macrophage colony-stimulating factor in a patient with benign systemic mastocytosis.

We report the in vitro and in vivo effects of granulocyte macrophage colony stimulating factor (GM‐CSF), a known inhibitor of in vitro mast cell differentiation, in a patient with benign, adult‐onset systemic mastocytosis. In vitro effects of GM‐CSF on bone marrow cultures before the start of treatment showed a marked inhibition of mast cell marker expression [tryptase, Kit, and high‐affinity IgE receptor (FcεRIα)] at both protein and mRNA levels. Therefore, the patient was treated with daily injections of GM‐CSF for 10 weeks. After an initial improvement, increasing worsening of clinical symptoms was noted, and the patient refused further treatment. Lesional skin biopsies showed an increase of toluidine blue‐positive mast cells, compared with uninvolved skin, with further significant increase after treatment. Similar results were obtained on staining for mast cell‐specific tryptase and Kit, as well as for CD1a and FcεRIα. These findings show that GM‐CSF inhibits human bone marrow mast cell differentiation in vitro, and also in mastocytosis. However, GM‐CSF apparently enhances recruitment of mast cell as well as dendritic cell precursors into the tissue during systemic treatment. These findings and the observed adverse clinical effects in the present patient make it unlikely that GM‐CSF monotherapy will be beneficial for the treatment of mastocytosis.

Chronische Urtikaria: diagnostisches und therapeutisches Vorgehen

Die chronische Urtikaria wird von den meisten Arzten gefurchtet, weil die Suche nach den vielfaltigen Ursachen zeitaufwendig, oft unergiebig und entsprechend frustrierend ist [1–4]. Die Identifizierung des Auslosers bildet jedoch die wesentliche Voraussetzung fur eine nicht nur palliative, sondern auch kurative Therapie der Krankheit. Die hier aufgefuhrten allgemeinen diagnostischen Grundlagen (Tabelle 1) sollen eine einfache Handhabe bieten, den Prozes der Diagnosestellung einfach, praktisch, logisch und so ergiebig wie moglich zu gestalten.