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Allergen Immunotherapy

People with insect venom allergy suffer from life threatening reactions which may severely impact their quality of life.
In patients with the most severe allergic reactions, these reactions might be due to underlying mastocytosis, which is a disease of mast cells that are, due to a mutation, increased in amount and also more trigger happy. Insect venom is able to easily trigger these mastcells, resulting in very severe, sometimes even fatal reactions. There are many unresolved questions in insect venom allergic patients who suffer from underlying mastocytosis. Firstly it is unknown which patients are at risk for underlying mastocytosis and secondly, what is the best diagnostic tool to evaluate for this disease. Also, if the diagnosis mastocytosis has been made, many questions still have to be answered.
Especially in patients with an underlying mastocytosis the diagnosis insect venom allergy is sometimes difficult due to absence of specific allergic symptoms, and/or due to absent or very low amounts of specific IgE. Also, concerning best treatment there are many open questions: there is no consensus whether treatment with immunotherapy should be started, which treatment schedules should be used, and for how long patients should be treated.
In this task force we will describe the current gaps in our knowledge concerning above mentioned issues and we will discuss with the most renowned allergist in this field their opinion in order to increase awareness of mastocytosis as underlying disease in insect venom allergy and to improve diagnosis and treatment of this allergy in patients with underlying mastocytosis.

Working Group: Insect venom hypersensitivity
Chair: Hanneke Oude Elberink
Secretary: Merel Onnes
Hayfever induced by inhalant allergen affects 10-15% of children with a prevalence of 23% in Europe for children and adult population. Allergen immunotherapy (AIT) involves administration of the sensitising allergen subcutaneously or sublingually for a period of at least 3 years and is safe and clinically effective in adults and children suffering from hayfever with or without asthma. Most AIT studies, SCIT and SLIT, use biomarkers, or changes in the immune response that have been validated in adults and not in children. There is a misconception that changes in immune response to AIT in children are similar to adults. However, there is a lack of studies that provide a head-to-head comparison between change in immune response in children and in adults. Thus, no consensus on immune changes in response AIT in children and adult.
The aim of the Task Force is firstly, to assess the immune parameters in adult and children, evaluate their usefulness for clinical studies and develop a concept for an age-adapted population to ensure both adults and children benefit from AIT. Secondly, to evaluate the current evidence and utility of machine-based algorithms as a part of artificial intelligence for biomarker discovery. Finally, to provide a consensus based on evidence and real-life data.

Interest Group: Allergen Immunotherapy
Chair: Mohamed Shamji
Secretary: Montserrat Alvaro Lozano
Insect stings or bites can induce large local reactions or systemic reactions. Since decades, research has been focused particularly on bee and vespid allergy.
However, other hymenoptera can cause allergy as well. Depending on the geographic distribution, fire ants (e.g. In the US) and black jumper ants (e.g. in Australia) are responsible for local or systemic allergic reactions. Moreover, systemic reactions to horseflies have been reported. It is also well known that large local reactions to mosquito bites are frequently seen in Northern Europe.
Venom from bumblebees is considered similar to bee venom. However, there is evidence that if bumblebees are the primary sensitizers, bee venom maybe not sufficient to treat bumblebee venom allergy. Similarly, venom from hornets (Vespa crabro) maybe different from vespid venom. Moreover, sting reactions to “new” hymenoptera such as Vespa velutina were reported but no data exist on the diagnostic and therapeutic options.
Case series of IgE-mediated allergy to Argas reflexus, a pigeon’s tick responsible of typical nocturnal anaphylaxis, have been published as well. Currently there is no review or position paper available addressing rare insect allergy. Allergies to rare insects may be overlooked because of lacking knowledge. This position paper should be helpful to clinicians to create awareness and to improve clinical management of patients with these rare allergies.

Working Group: Insect venom hypersensitivity
Chair: Gunter Sturm
Secretary: Elisa Boni
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Allergy is already the most common chronic disease in children and young adults, and it keeps increasing worldwide. It is clear that the burden of allergic diseases is so large that it cannot be met globally by allergy specialists alone. The support of primary care physicians is indispensable in the management, treatment and diagnosis of these diseases. However, primary care clinicians are not trained adequately to manage allergic patients, creating a need to establish specialized education in allergy. Many medical postgraduate training programs, for example, have been established to allow the development of competencies in the diagnosis and management of allergic diseases. Nevertheless, these should always cover the latest hallmarks in the field. Allergen immunotherapy (AIT) is an example of a groundbreaking treatment in the field of allergy and this Task Force will investigate the knowledge of primary care specialists in the field. The goal is to discover if this important treatment, AIT, is being provided across Europe adequately and make recommendations to better identify in which cases the patient should be referred to specialist care. With this work, the Task Force hopes to get a solid understanding of the knowledge on AIT by primary care specialists and address their needs and gaps to support better allergy treatment.


Interest Group: Allied Health and Primary Care
Chair: Gawlik Radoslaw
Secretary: Bertine Flokstra-de Blak

Relevant literature: 

- Ryan, D. et al. Challenges in the implementation of the EAACI AIT guidelines: A situational analysis of current provision of allergen immunotherapy
Phase I: An interdisciplinary Task Force of the Immunotherapy Interest Group and the Aerobiology and Pollution Interest Group of the EAACI (2015-2016) has recently published standardized definitions for pollen seasons (birch ( Betula sp..), grasses (Poaceae), Cypress (Cupressus spp.), Olive (Olea spp.), Ragweed (Ambrosia spp.)) in an EAACI Position Paper (#1).
Phase II: In a next step, an international cooperation of allergologists, aerobiologists and environmental informatics experts demonstrated the robustness and sensitivity of the aforementioned season defintions in a retrospective analysis of pollen count data from up to 40 pollen monitoring stations in Germany over five consecutive years (2012-2016) (#2).
Ref:#1: Pfaar O, Bastl U, Berger U et al.: Definiing pollen exposure times for clinical trials of allergen immunotherapy for pollen-induced rhinoconjunctivitis – an EAACI position paper. Allergy 2017; 72: 713-722
#2: Karatzas K, Riga M, Berger U , Werchan M, Pfaar O, Bergmann KC: Computational validation of the recently proposed pollen season definition criteria. Allerry 2017: doi 10.1111/all. 13255

Chair: Oliver Pfaar
Secretary: Christian Bergmann
Allergen-Immunotherapy is effective and safe but time-consuming. Patient adherence is critical for its beneficial effects. The aim of our taskforce is to evaluate the published evidence to optimize adherence for patients and to provide instruments to patients and health professionals to optimize the use of this critical lever in the treatment of allergic diseases.

Chair: Adam Chaker
Secretary: Mohamed Shamji
Allergen exposure chambers (AECs) are clinical facilities that allow controlled exposure of subjects to allergens in an enclosed environment, in order to determine allergen sensitivity. AECs have contributed towards characterizing the pathophysiology of respiratory allergic diseases and the pharmacological properties of new therapies. To date, AEC studies conducted have been monocentric, meaning that they have followed protocols unique to each centre. Because there are technical differences among AECs, it may be necessary to define parameters to standardize the AECs so that studies may be extrapolated for driving basic immunological research and for marketing authorization purposes by regulatory authorities.
This task force not only aims to address the standardization of AECs but has also, in a previous study, pin-pointed that standardization of "hybrid"-trials in AIT needs further clinical validation. Together with international scientists, clinicians, representatives from EMA and FDA, the main aim of this task force is to elaborate the principle of a multicenter "hybrid"-trial in AIT.
 
Chair: Oliver Pfaar
Secretary: Petra Zieglmayer

Relevant literature:

- Pfaar, O et al. Allergen exposure chambers: harmonizing current concepts and projecting the needs for the future - an EAACI position paper
pillAsthma is long-term inflammation of the airways of the lungs, and affects 235-330 million people worldwide. This common disease in the Western World usually starts in early life and has a substantial impact on the patient's quality of life. Management of asthma can be achieved by avoidance of the allergen, or treated with pharmacotherapeutics. However, when these are not sufficient to give the patient an acceptable quality of life, allergen immunotherapy (AIT) can be recommended. Treatment with AIT extends from a period of 3 to 5 years and during this time the patient is closely monitored to determine the effect of the treatment. However, there is no current European consensus on how to monitor the effect of AIT in asthma patients. This poses a problem when comparing results from different treatment centers and, ultimately, impairs the optimization of the treatment.
This task force aims to address this issue by presenting a consensus in monitoring the clinical outcomes of AIT in asthma patients, both in a clinical and a research setting.



Interest Group: Allergen Immunotherapy
Chair: Jasper Kappen
Secretary: Oliver Pfaar

Relevant literature: 

- Jutel M. et al. International consensus on allergy immunotherapy

- Pfaar O. et al. Recommendations for the standardization of clinical outcomes used in allergen immunotherapy trials fro allergic rhinoconjunctivitis: an EAACI position paper

- Pfaar O. et al. Clinical trials in allergen immunotherapy: current concepts and future needs

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A placebo is a substance that does not have any therapeutic value. Commonly, placebos are administered in clinical trials to the control set of patients (control group). In this way, the effects of the drug being tested on a certain patient group can be compared with the control group to determine the efficiency of the drug. In certain trials, the placebo groups have shown improvement of the disease despite not being prescribed a therapeutic compound. This phenomenon is called the placebo effect and is harmful for the outcome and conclusions of the trial because it impairs determining the real benefit caused by the active component.
In allergen immunotherapy (AIT) there is a quite a large report of placebo effects, increasing the need to rethink the design of AIT clinical trials, including the selection of the placebo.
Together, the group of experts in this task force aim to review the basis of placebo effects in AIT and investigate the relevance of placebo effects in these clinical trials.

Interest Group: Allergen Immunotherapy
Chair: Oliver Pfaar

Relevant literature: 

- Frew, A. & Pfaar O. Placebo effects in allergen immunotherapy: an experts' opinion

- Narkus, A. et al. The placebo effect in allergen-specific immunotherapy trials

- Frew, A. et al. Assessment of specific immunotherapy efficacy using a novel placebo score-based method




After a quick run down memory lane, Sergio Bonini explains the placebo effect, most recent discoveries and exciting suggestions to circumvent this problem in AIT clinical trials.