Publications by authors named "Bettina Wedi"

50 Publications

Wheat Anaphylaxis in Adults Differs from Reactions to Other Types of Food.

J Allergy Clin Immunol Pract 2021 Apr 5. Epub 2021 Apr 5.

Division of Allergy and Immunology, Department of Dermatology, Venerology and Allergology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany. Electronic address:

Background: Wheat is one of the most commonly consumed foods and a known elicitor of anaphylaxis in children and adults. Reactions in adults are often cofactor dependent and characterized by a prolonged time between food intake and the onset of symptoms making the diagnosis of wheat anaphylaxis challenging.

Objective: To characterize a cohort of patients with the history of wheat anaphylaxis to better understand this atypical phenotype of anaphylaxis.

Methods: Data from the European Anaphylaxis Registry from 2007 to 2019 (n = 10,636) including 250 patients (213 adults and 37 children) with a history of anaphylaxis caused by wheat were analyzed.

Results: Wheat was the most common food elicitor of anaphylaxis in adults in the registry in Central Europe. Reactions to wheat in adults were frequently associated with exercise as a cofactor (82.8%) and partially delayed (57.5%). Only 36.9% of patients had atopic comorbidities, which was uncommonly low for adult patients allergic to other kinds of foods (63.2%). Anaphylaxis to wheat presented frequently with cardiovascular symptoms (86.7%) including severe symptoms such as loss of consciousness (41%) and less often with respiratory symptoms (53.6%). The reactions to wheat were more severe than reactions to other foods (odds ratio [OR] = 4.33), venom (OR = 1.58), or drugs (OR = 2.11).

Conclusions: Wheat is a relevant elicitor of anaphylaxis in adults in Central Europe. Wheat anaphylaxis is highly dependent on the presence of cofactors and less frequently associated with atopic diseases compared with other food allergies. More data on mechanisms of wheat-induced anaphylaxis are required to develop preventive measures for this potentially life-threatening disease.
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http://dx.doi.org/10.1016/j.jaip.2021.03.037DOI Listing
April 2021

Expert consensus on practical aspects in the treatment of chronic urticaria.

Allergo J Int 2021 24;30(2):64-75. Epub 2021 Feb 24.

Department of Dermatology and Allergy, Urticaria Center of Reference and Excellence (UCARE), Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.

Background: Chronic urticaria (CU) is a common disease which represents a considerable burden for many patients. The current urticaria guideline describes the evidence-based diagnosis and treatment of CU. In addition, however, questions often arise in everyday practice that are not addressed by the guideline.

Methods: In May 2020, a digital meeting with German urticaria experts was held, in which practical aspects of CU treatment were discussed and supporting aids for everyday clinical treatment formulated. The resulting advice in this document focus on practical questions and the available literature and experiences of the participants.

Results: The diagnosis of CU can be made in a short time by means of a thorough anamnesis, a physical examination, and a basic laboratory chemical diagnosis. For this purpose, practical recommendations for everyday practice are given in this paper. An extended diagnosis is only indicated in a few cases and should always be carried out in parallel with an effective therapy. In general, CU should always be treated in the same way, regardless of whether wheals, angioedema or both occur. Symptomatic therapy should be carried out according to the treatment steps recommended by the guidelines. This publication provides practical advice on issues in everyday practice, such as the procedure in the current coronavirus disease 2019 (COVID-19) pandemic, the cardiac risk under higher dosed H1 antihistamines, the self-administration of omalizumab as well as vaccination under omalizumab therapy. In addition to treatment recommendations, topics such as documentation in the practice and family planning with urticaria will be discussed.

Discussion: These supporting treatment recommendations serve as an addendum to the current CU guideline and provide support in dealing with CU patients in everyday practice. The aim is to ensure that patients suffering from CU achieve complete freedom of symptoms with the help of an optimal therapy.

Supplementary Information: The online version of this article (10.1007/s40629-021-00162-w) contains supplementary material, which is available to authorized users.
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http://dx.doi.org/10.1007/s40629-021-00162-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903036PMC
February 2021

Anti-IgE for the Treatment of Chronic Urticaria.

Immunotargets Ther 2021 17;10:27-45. Epub 2021 Feb 17.

Department of Dermatology and Allergy, Comprehensive Allergy Center, Hannover Medical School, Hannover, Germany.

Urticaria and angioedema are very common. Management of chronic urticaria subtypes, which usually persist for many years, is challenging. Recent years have demonstrated that targeting IgE with antibodies provides a safe and efficient treatment approach. Whilst several anti-IgE antibodies have been developed, omalizumab is currently the only one approved for use. International and national guidelines recommend its use after failure of antihistamines at standard and increased dose. Whilst not yet approved, many new anti-IgE approaches are currently being investigated in pre-clinical studies or clinical trials. This non-systematic focused review summarizes current knowledge of omalizumab and other anti-IgE biologics in chronic urticaria using data extracted from PubMed, Google Scholar and clinical trial databases, clinicaltrials.gov and clinicaltrials.eu. For adults, there is good evidence from randomized clinical trials and real-world data that symptomatic treatment with omalizumab is efficacious and safe in chronic spontaneous urticaria (CSU), whereas evidence in chronic inducible urticaria (CINDU) and special populations is limited. Easy-to-use tools to identify non-responders and predict the required duration of treatment have not been established yet. Phase 2 b results of ligelizumab have not only demonstrated efficacy and safety but also superiority to omalizumab. Indeed, there is preliminary evidence that omalizumab non- or partial responders benefit from ligelizumab. Whereas further development of quilizumab was discontinued, other approaches, eg UB-221 or DARPins are under investigation. Anti-IgE treatment with omalizumab represents a landmark in the treatment of chronic urticaria, with and without angioedema, and there is light on the horizon suggesting success may come with various next-generation anti-IgE approaches.
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http://dx.doi.org/10.2147/ITT.S261416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898214PMC
February 2021

Practical recommendations for the allergological risk assessment of the COVID-19 vaccination - a harmonized statement of allergy centers in Germany.

Allergol Select 2021 26;5:72-76. Epub 2021 Jan 26.

Allergy and Asthma Center Westend, Berlin, Germany.

Severe allergic reactions to vaccines are very rare. Single severe reactions have occurred worldwide after vaccination with the new mRNA-based COVID-19 vaccines. PEG2000 is discussed as a possible trigger. We provide guidance on risk assessment regarding COVID-19 vaccination in patients with allergic diseases and suggest a standardized, resource-oriented diagnostic and therapeutic procedure. Reports of severe allergic reactions in the context of COVID-19 vaccination can be made via www.anaphylaxie.net using an online questionnaire.
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http://dx.doi.org/10.5414/ALX02225EDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841415PMC
January 2021

Healthcare provision for insect venom allergy patients during the COVID-19 pandemic.

Allergo J Int 2020 8;29(8):257-261. Epub 2020 Dec 8.

Department and Outpatient Clinic for Dermatology and Allergology, University Hospital Munich, Munich, Germany.

The population prevalence of insect venom allergy ranges between 3-5%, and it can lead to potentially life-threatening allergic reactions. Patients who have experienced a systemic allergic reaction following an insect sting should be referred to an allergy specialist for diagnosis and treatment. Due to the widespread reduction in outpatient and inpatient care capacities in recent months as a result of the COVID-19 pandemic, the various allergy specialized centers in Germany, Austria, and Switzerland have taken different measures to ensure that patients with insect venom allergy will continue to receive optimal allergy care. A recent data analysis from the various centers revealed that there has been a major reduction in newly initiated insect venom immunotherapy (a 48.5% decline from March-June 2019 compared to March-June 2020: data from various centers in Germany, Austria, and Switzerland). The present article proposes defined organizational measures (e.g., telephone and video appointments, rearranging waiting areas and implementing hygiene measures and social distancing rules at stable patient numbers) and medical measures (collaboration with practice-based physicians with regard to primary diagnostics, rapid COVID-19 testing, continuing already-initiated insect venom immunotherapy in the outpatient setting by making use of the maximal permitted injection intervals, prompt initiation of insect venom immunotherapy during the summer season, and, where necessary, using outpatient regimens particularly out of season) for the care of insect venom allergy patients during the COVID-19 pandemic.
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http://dx.doi.org/10.1007/s40629-020-00157-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722411PMC
December 2020

The global impact of the COVID-19 pandemic on the management and course of chronic urticaria.

Allergy 2021 03 29;76(3):816-830. Epub 2020 Dec 29.

Urticaria Center of Reference and Excellence (UCARE), Department of Dermatology and Venereology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

Introduction: The COVID-19 pandemic dramatically disrupts health care around the globe. The impact of the pandemic on chronic urticaria (CU) and its management are largely unknown.

Aim: To understand how CU patients are affected by the COVID-19 pandemic; how specialists alter CU patient management; and the course of CU in patients with COVID-19.

Materials And Methods: Our cross-sectional, international, questionnaire-based, multicenter UCARE COVID-CU study assessed the impact of the pandemic on patient consultations, remote treatment, changes in medications, and clinical consequences.

Results: The COVID-19 pandemic severely impairs CU patient care, with less than 50% of the weekly numbers of patients treated as compared to before the pandemic. Reduced patient referrals and clinic hours were the major reasons. Almost half of responding UCARE physicians were involved in COVID-19 patient care, which negatively impacted on the care of urticaria patients. The rate of face-to-face consultations decreased by 62%, from 90% to less than half, whereas the rate of remote consultations increased by more than 600%, from one in 10 to more than two thirds. Cyclosporine and systemic corticosteroids, but not antihistamines or omalizumab, are used less during the pandemic. CU does not affect the course of COVID-19, but COVID-19 results in CU exacerbation in one of three patients, with higher rates in patients with severe COVID-19.

Conclusions: The COVID-19 pandemic brings major changes and challenges for CU patients and their physicians. The long-term consequences of these changes, especially the increased use of remote consultations, require careful evaluation.
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http://dx.doi.org/10.1111/all.14687DOI Listing
March 2021

Reply to Sabato V et al "Surface expression of MRGPRX2 expression on resting basophils: An area of controversy".

Allergy 2020 09;75(9):2424-2427

Department of Dermatology and Allergy, Comprehensive Allergy Center, Hannover Medical School, Hannover, Germany.

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http://dx.doi.org/10.1111/all.14446DOI Listing
September 2020

[Are cationic amphiphilic H1 antihistamines useful as adjuvant treatment of malignant melanoma?]

Authors:
Bettina Wedi

Hautarzt 2020 Aug;71(8):653-655

Klinik für Dermatologie, Allergologie und Venerologie, Comprehensive Allergy Center (CAC), Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Deutschland.

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http://dx.doi.org/10.1007/s00105-020-04652-wDOI Listing
August 2020

Phenotype and risk factors of venom-induced anaphylaxis: A case-control study of the European Anaphylaxis Registry.

J Allergy Clin Immunol 2021 Feb 22;147(2):653-662.e9. Epub 2020 Jun 22.

Division of Allergy and Immunology, Department of Dermatology, Venerology, and Allergology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany. Electronic address:

Background: Venom-induced anaphylaxis (VIA) is a common, potentially life-threatening hypersensitivity reaction associated with (1) a specific symptom profile, 2) specific cofactors, and 3) specific management. Identifying the differences in phenotypes of anaphylaxis is crucial for future management guidelines and development of a personalized medicine approach.

Objective: This study aimed to evaluate the phenotype and risk factors of VIA.

Methods: Using data from the European Anaphylaxis Registry (12,874 cases), we identified 3,612 patients with VIA and analyzed their cases in comparison with sex- and age-matched anaphylaxis cases triggered by other elicitors (non-VIA cases [n = 3,605]).

Results: VIA more frequently involved more than 3 organ systems and was associated with cardiovascular symptoms. The absence of skin symptoms during anaphylaxis was correlated with baseline serum tryptase level and was associated with an increased risk of a severe reaction. Intramuscular or intravenous epinephrine was administered significantly less often in VIA, in particular, in patients without a history of anaphylaxis. A baseline serum tryptase level within the upper normal range (8-11.5 ng/mL) was more frequently associated with severe anaphylaxis.

Conclusion: Using a large cohort of VIA cases, we have validated that patients with intermediate baseline serum tryptase levels (8-11 ng/mL) and without skin involvement have a higher risk of severe VIA. Patients receiving β-blockers or angiotensin-converting enzyme inhibitors had a higher risk of developing severe cardiovascular symptoms (including cardiac arrest) in VIA and non-VIA cases. Patients experiencing VIA received epinephrine less frequently than did cases with non-VIA.
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http://dx.doi.org/10.1016/j.jaci.2020.06.008DOI Listing
February 2021

Guideline on diagnostic procedures for suspected hypersensitivity to beta-lactam antibiotics: Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) in collaboration with the German Society of Allergology (AeDA), German Society for Pediatric Allergology and Environmental Medicine (GPA), the German Contact Dermatitis Research Group (DKG), the Austrian Society for Allergology and Immunology (ÖGAI), and the Paul-Ehrlich Society for Chemotherapy (PEG).

Allergol Select 2020 28;4:11-43. Epub 2020 May 28.

Department of Dermatology and Allergology am Biederstein, School of Medicine, Technical University of Munich, Munich, Germany.

This guideline on diagnostic procedures for suspected beta-lactam antibiotic (BLA) hypersensitivity was written by the German and Austrian professional associations for allergology, and the Paul-Ehrlich Society for Chemotherapy in a consensus procedure according to the criteria of the German Association of Scientific Medical Societies. BLA such as penicillins and cephalosporins represent the drug group that most frequently triggers drug allergies. However, the frequency of reports of suspected allergy in patient histories clearly exceeds the number of confirmed cases. The large number of suspected BLA allergies has a significant impact on, e.g., the quality of treatment received by the individual patient and the costs to society as a whole. Allergies to BLA are based on different immunological mechanisms and often manifest as maculopapular exanthema, as well as anaphylaxis; and there are also a number of less frequent special clinical manifestations of drug allergic reactions. All BLA have a beta-lactam ring. BLA are categorized into different classes: penicillins, cephalosporins, carbapenems, monobactams, and beta-lactamase inhibitors with different chemical structures. Knowledge of possible cross-reactivity is of considerable clinical significance. Whereas allergy to the common beta-lactam ring occurs in only a small percentage of all BLA allergic patients, cross-reactivity due to side chain similarities, such as aminopenicillins and aminocephalosporins, and even methoxyimino cephalosporins, are more common. However, the overall picture is complex and its elucidation may require further research. Diagnostic procedures used in BLA allergy are usually made up of four components: patient history, laboratory diagnostics, skin testing (which is particularly important), and drug provocation testing. The diagnostic approach - even in cases where the need to administer a BLA is acute - is guided by patient history and risk - benefit ratio in the individual case. Here again, further studies are required to extend the present state of knowledge. Performing allergy testing for suspected BLA hypersensitivity is urgently recommended not only in the interests of providing the patient with good medical care, but also due to the immense impact of putative BLA allergies on society as a whole.
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http://dx.doi.org/10.5414/ALX02104EDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304290PMC
May 2020

Hypersensitivity reactions to biologics (part I): allergy as an important differential diagnosis in complex immune-derived adverse events.

Allergo J 2020 24;29(4):32-61. Epub 2020 Jun 24.

Klinische und Molekulare Allergologie - Forschungszentrum Borstel, Parkallee 35, 23845 Borstel, Germany.

Biotechnological substances (BSs) are strongly relied upon to prevent rejection of transplanted organs, and to treat oncological, allergological, and other inflammatory diseases. Allergic reactions to partly foreign biologics can occur due to their potential immunogenicity. The severity of an immune response to a biological drug may range from no clinical significance to a severe, life-threatening anaphylactic reaction. Detailed searches were performed on Pubmed, Web of Science, and Google Scholar to include all available publications. In addition, the Food and Drug Administration, the European Medicines Agency, and British Columbia Cancer Agency Drug Manual databases were screened for hypersensitivity reaction (HSR), infusion reaction, injection site reaction, urticaria, and anaphylaxis for individual BSs. Treatment with BSs can cause various types of HSR. These are mentioned in the literature with definitions such as allergic reactions, anaphylactoid reactions, anaphylaxis, HSR, infusion reactions, injection site reactions, cytokine release syndrome, and urticaria. Due to the overlap in signs and symptoms in the reported descriptions, it is not always possible to differentiate these reactions properly according to their pathomechanism. Similarly, many data reported as anaphylaxis actually describe severe anaphylactic reactions (grades III or IV). There is an urgent need for a simpler symptom- or system-based classification and scoring system to create an awareness for HSRs to BSs. A better understanding of the pathophysiology of HSRs and increased clinical experience in the treatment of side effects will provide timely control of unexpected reactions. As a result, immunotherapy with BSs will become safer in the future., , allergy as an important differential diagnosis in complex immune-derived adverse events. Allergo J Int 2020; 29:97-125//doi.org/10.1007/s40629-020-00126-6.
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http://dx.doi.org/10.1007/s15007-020-2550-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289641PMC
June 2020

Hypersensitivity reactions to biologics (part I): allergy as an important differential diagnosis in complex immune-derived adverse events.

Allergo J Int 2020 12;29(4):97-125. Epub 2020 May 12.

Division of Clinical and Molecular Allergology, Airway Research Center North (ARCN), Member of the German Center for Lung Research, Research Center Borstel, Parkallee 35, 23845 Borstel, Germany.

Purpose: Biotechnological substances (BSs) are strongly relied upon to prevent rejection of transplanted organs, and to treat oncological, allergological, and other inflammatory diseases. Allergic reactions to partly foreign biologics can occur due to their potential immunogenicity. The severity of an immune response to a biological drug may range from no clinical significance to a severe, life-threatening anaphylactic reaction.

Methods: Detailed searches were performed on Pubmed, Web of Science, and Google Scholar to include all available publications. In addition, the Food and Drug Administration, the European Medicines Agency, and British Columbia Cancer Agency Drug Manual databases were screened for hypersensitivity reaction (HSR), infusion reaction, injection site reaction, urticaria, and anaphylaxis for individual BSs.

Results: Treatment with BSs can cause various types of HSR. These are mentioned in the literature with definitions such as allergic reactions, anaphylactoid reactions, anaphylaxis, HSR, infusion reactions, injection site reactions, cytokine release syndrome, and urticaria. Due to the overlap in signs and symptoms in the reported descriptions, it is not always possible to differentiate these reactions properly according to their pathomechanism. Similarly, many data reported as anaphylaxis actually describe severe anaphylactic reactions (grades III or IV).

Conclusion: There is an urgent need for a simpler symptom- or system-based classification and scoring system to create an awareness for HSRs to BSs. A better understanding of the pathophysiology of HSRs and increased clinical experience in the treatment of side effects will provide timely control of unexpected reactions. As a result, immunotherapy with BSs will become safer in the future.
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http://dx.doi.org/10.1007/s40629-020-00126-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223134PMC
May 2020

Ligelizumab for the treatment of chronic spontaneous urticaria.

Authors:
Bettina Wedi

Expert Opin Biol Ther 2020 08 19;20(8):853-861. Epub 2020 May 19.

Department of Dermatology and Allergy, Comprehensive Allergy Center, Hannover Medical School , Hannover, Germany.

Introduction: Due to daily hives with itch, sleeplessness, and unforeseen development of angioedema, chronic spontaneous urticaria significantly impairs quality of life, often for years. Its management is challenging. In most cases, H1-antihistamines are not effective. Although the disease is not characterized by specific IgE antibodies against allergens, the last decade demonstrated that neutralizing IgE by using the monoclonal anti-IgE antibody Omalizumab is safe and effective. Nevertheless, symptoms are not controlled by Omalizumab in approximately one-fourth of patients.

Areas Covered: This review is focused on Ligelizumab (QGE031), a next-generation non-triggering fully human monoclonal antibody, with higher affinity to IgE compared to Omalizumab.

Expert Opinion: In chronic spontaneous urticaria, subcutaneous Ligelizumab once per month for five months has shown a clear dose-response relationship with respect to symptoms. Superiority over Omalizumab was noted whereas the safety profile was similar. Most common side effects were injection site reactions. In the near future, results from phase 3 trials, two of them including more than 1000 patients each, are awaited. Having a higher affinity to IgE and being more effective than Omalizumab, Ligelizumab has the potential to free chronic urticaria patients from year-long daily annoying symptoms that did not respond to standard therapy as recommended by current guidelines.
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http://dx.doi.org/10.1080/14712598.2020.1767061DOI Listing
August 2020

Placebo effects in allergen immunotherapy-An EAACI Task Force Position Paper.

Allergy 2021 03;76(3):629-647

Department of Respiratory Medicine, Royal Sussex County Hospital, University of Sussex and University of Brighton, Brighton, UK.

The placebo (Latin "I will please") effect commonly occurs in clinical trials. The psychological and physiological factors associated with patients' expectations about a treatment's positive and negative effects have yet to be well characterized, although a functional prefrontal cortex and intense bidirectional communication between the central nervous system and the immune system appear to be prerequisites for a placebo effect. The use of placebo raises certain ethical issues, especially if patients in a placebo group are denied an effective treatment for a long period of time. The placebo effect appears to be relatively large (up to 77%, relative to pretreatment scores) in controlled clinical trials of allergen immunotherapy (AIT), such as the pivotal, double-blind, placebo-controlled (DBPC) randomized clinical trials currently required by regulatory authorities worldwide. The European Academy of Allergy and Clinical Immunology (EAACI) therefore initiated a Task Force, in order to better understand the placebo effect in AIT and its specific role in comorbidities, blinding issues, adherence, measurement time points, variability and the natural course of the disease. In this Position Paper, the EAACI Task Force highlights several important topics regarding the placebo effect in AIT such as a) regulatory aspects, b) neuroimmunological and psychological mechanisms, c) placebo effect sizes in AIT trials, d) methodological limitations in AIT trial design and e) potential solutions in future AIT trial design. In conclusion, this Position Paper aims to examine the methodological problem of placebo in AIT from different aspects and also to highlight unmet needs and possible solutions for future trials.
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http://dx.doi.org/10.1111/all.14331DOI Listing
March 2021

The pseudoallergen receptor MRGPRX2 on peripheral blood basophils and eosinophils: Expression and function.

Allergy 2020 09 15;75(9):2229-2242. Epub 2020 Feb 15.

Department of Dermatology and Allergy, Comprehensive Allergy Center, Hannover Medical School, Hannover, Germany.

Background: Mas-related G protein-coupled receptor X2 (MRGPRX2) is regarded as a mast cell-specific receptor mediating non-IgE-dependent activation. We aimed to investigate whether human basophils and eosinophils express functional MRGPRX2.

Methods: Flow cytometry, immunocytochemistry, immunofluorescence, Western blot, and RT-PCR were performed in highly purified peripheral blood basophils and eosinophils of atopic and nonatopic donors. To assess functional activity, fluorescent avidin-based degranulation assay, calcium mobilization, cytokine production in supernatants, assessment of viability/apoptosis, and tricolor granulocyte activation test were used.

Results: MRGPRX2 was significantly expressed by basophils and eosinophils but not neutrophils. Functional capacity was shown by anti-MRGPRX2 mAb-induced calcium influx and concentration-dependent induction of degranulation. Sequential stimulation in the calcium mobilization assay gave no evidence for desensitization or receptor internalization. Anti-MRGPRX2 mAb significantly promoted survival. Inhibition of apoptosis could be due to released IL-3, IL-5, and GM-CSF found in supernatants. Short-term incubation with IL-3 dose-dependently upregulated MRGPRX2 expression in both, stimulation for 24 hours with anti-IgE, C5a, fMLP, and IL-3 in basophils and by IL-3, IL-5, and IL-33 in eosinophils. Among known mast cell MRGPRX2 agonists ciprofloxacin but not PMX-53 was functional on basophils and eosinophils. In basophils of allergic subjects, tricolor granulocyte activation test using grass pollen demonstrated MRGPRX2 upregulation associated with degranulation and CD63 expression.

Conclusion: Unraveling the regulation and signaling mechanisms of MRGPRX2 on basophils and eosinophils might enable the development of new therapeutic strategies to prevent or inhibit allergic and nonallergic hypersensitivity. Moreover, addressing MRGPRX2 might have potential for diagnostic purposes in (drug) hypersensitivity.
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http://dx.doi.org/10.1111/all.14213DOI Listing
September 2020

Secondary prevention measures in anaphylaxis patients: Data from the anaphylaxis registry.

Allergy 2020 04 21;75(4):901-910. Epub 2019 Oct 21.

Division of Allergy and Immunology, Department of Dermatology Venerology and Allergology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.

Background: Patients with a history of anaphylaxis are at risk of future anaphylactic reactions. Thus, secondary prevention measures are recommended for these patients to prevent or attenuate the next reaction.

Methods: Data from the Anaphylaxis Registry were analyzed to identify secondary prevention measures offered to patients who experienced anaphylaxis. Our analysis included 7788 cases from 10 European countries and Brazil.

Results: The secondary prevention measures offered varied across the elicitors. A remarkable discrepancy was observed between prevention measures offered in specialized allergy centers (84% of patients were prescribed adrenaline autoinjectors following EAACI guidelines) and outside the centers: Here, EAACI guideline adherence was only 37%. In the multivariate analysis, the elicitor of the reaction, age of the patient, mastocytosis as comorbidity, severity of the reaction, and reimbursement/availability of the autoinjector influence physician's decision to prescribe one.

Conclusions: Based on the low implementation of guidelines concerning secondary prevention measures outside of specialized allergy centers, our findings highlight the importance of these specialized centers and the requirement of better education for primary healthcare and emergency physicians.
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http://dx.doi.org/10.1111/all.14069DOI Listing
April 2020

Ligelizumab for Chronic Spontaneous Urticaria.

N Engl J Med 2019 10;381(14):1321-1332

From the Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Berlin (M. Maurer, M. Metz), the Department of Dermatology, University Allergy Center, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden (A. Bauer), the Department of Dermatology, University Hospital Münster, Münster (R.B.), the Department of Dermatology, University Medical Center Mainz, Mainz (P.S.), and the Department of Dermatology and Allergy, Comprehensive Allergy Center, Hannover Medical School, Hannover (B.W.) - all in Germany; the Dermatology Department, Hospital del Mar-Institut Hospital del Mar d'Investigacions Mèdiques, Universitat Autònoma Barcelona, Barcelona (A.M.G.-A.); the Division of Allergy and Clinical Immunology, St. Michael's Hospital and University of Toronto, Toronto (G.S.), Service d'Allergie, Centre Hospitalier Université Laval-Centre Hospitalier Universitaire de Québec, Quebec, QC (J.H.), and the Department of Medicine, University of Ottawa, Ottawa (K.K.) - all in Canada; Baker Allergy Asthma and Dermatology Clinic, Portland, OR (D.R.B.); University of Cincinnati College of Medicine, Department of Internal Medicine, Division of Immunology, Rheumatology, and Allergy and Bernstein Clinical Research Center, Cincinnati (J.A.B.); the Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine (C.-Y.C.), and the Department of Dermatology, Chang Gung Memorial Hospital (W.-H.C.), Taipei, Taiwan; the National Research Center-Institute of Immunology Federal Medical-Biological Agency of Russia, Moscow (I.D.), and the Department of Clinical Immunology and Allergology, Smolensk State Medical University, Smolensk (R.M.) - both in Russia; St. John's Institute of Dermatology, Guy's and St. Thomas' Hospitals NHS Foundation Trust, London (C.G.), and the National Institute for Health Research-Leeds Biomedical Research Centre and Leeds Institute of Rheumatic and Musculoskeletal Medicine, and the Department of Clinical Immunology and Allergy, St. James's University Hospital, Leeds (S.S.) - all in the United Kingdom; the School of Medicine, Western Sydney University, and the Immunology and Allergy Unit, Campbelltown Hospital, Campbelltown, NSW (C.K.), and Sinclair Dermatology and the Epworth Hospital, Melbourne, VIC (R.S.) - all in Australia; the Second Department of Dermatology and Venereology, Attikon University Hospital, Athens (M. Makris); Little Rock Allergy and Asthma Clinic, Little Rock, AR (K.S.); Novartis Pharma, Basel, Switzerland (J.L., T.S., R.J.); Novartis Pharmaceuticals, East Hanover, NJ (A. Barve, K.K.); and Shanghai Novartis Trading, Shanghai, China (E.H.).

Background: In the majority of patients with chronic spontaneous urticaria, most currently available therapies do not result in complete symptom control. Ligelizumab is a next-generation high-affinity humanized monoclonal anti-IgE antibody. Data are limited regarding the dose-response relationship of ligelizumab and the efficacy and safety of ligelizumab as compared with omalizumab and placebo in patients who have moderate-to-severe chronic spontaneous urticaria that is inadequately controlled with H-antihistamines at approved or increased doses, alone or in combination with H-antihistamines or leukotriene-receptor antagonists.

Methods: In a phase 2b dose-finding trial, we randomly assigned patients to receive ligelizumab at a dose of 24 mg, 72 mg, or 240 mg, omalizumab at a dose of 300 mg, or placebo, administered subcutaneously every 4 weeks for a period of 20 weeks, or a single 120-mg dose of ligelizumab. Disease symptoms of hives, itch, and angioedema were monitored by means of weekly activity scores. The main objective was to determine a dose-response relationship for the complete control of hives (indicated by a weekly hives-severity score of 0, on a scale from 0 to 21, with higher scores indicating greater severity); the primary end point of this response was assessed at week 12. Complete symptom control was indicated by a weekly urticaria activity score of 0 (on a scale from 0 to 42, with higher scores indicating greater severity). Safety was analyzed throughout the trial.

Results: A total of 382 patients underwent randomization. At week 12, a total of 30%, 51%, and 42% of the patients treated with 24 mg, 72 mg, and 240 mg, respectively, of ligelizumab had complete control of hives, as compared with 26% of the patients in the omalizumab group and no patients in the placebo group. A dose-response relationship was established. At week 12, a total of 30%, 44%, and 40% of the patients treated with 24 mg, 72 mg, and 240 mg, respectively, of ligelizumab had complete control of symptoms, as compared with 26% of the patients in the omalizumab group and no patients in the placebo group. In this small and short trial, no safety concerns regarding ligelizumab or omalizumab emerged.

Conclusions: A higher percentage of patients had complete control of symptoms of chronic spontaneous urticaria with ligelizumab therapy of 72 mg or 240 mg than with omalizumab or placebo. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT02477332.).
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http://dx.doi.org/10.1056/NEJMoa1900408DOI Listing
October 2019

[Coming into focus: dipeptidyl peptidase 4 inhibitors (gliptins)].

Authors:
Bettina Wedi

Hautarzt 2019 May;70(5):388-391

Klinik für Dermatologie, Allergologie und Venerologie, Comprehensive Allergy Center (CAC), Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Deutschland.

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http://dx.doi.org/10.1007/s00105-019-4400-1DOI Listing
May 2019

[Correct recognition and treatment of angioedema].

Hautarzt 2019 Feb;70(2):82-83

Klinik für Dermatologie, Venerologie und Allergologie, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Deutschland.

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http://dx.doi.org/10.1007/s00105-018-4340-1DOI Listing
February 2019

Generalized reactions during skin testing with clindamycin in drug hypersensitivity: a report of 3 cases and review of the literature.

Contact Dermatitis 2018 Apr 22;78(4):274-280. Epub 2018 Jan 22.

Department of Dermatology and Allergy, Comprehensive Allergy Centre, Hannover Medical School, 30625, Hannover, Germany.

Background: The diagnostic approach to drug hypersensitivity includes a detailed medical history, clinical examination, and skin testing and/or oral challenge with a culprit or alternative drug, depending on the type of reaction and the suspected drugs. Although skin testing is considered to be rather safe, cutaneous and systemic, including fatal, reactions have been described.

Objectives: To report 3 cases with generalized delayed reactions after skin testing with clindamycin, and to review the existing literature.

Methods: Thorough clinical examination, blood tests and prick, intradermal and patch tests were performed in 3 patients.

Results: All patients experienced generalized maculopapular exanthema after intradermal and patch testing with clindamycin and amoxicillin in the first patient, and clindamycin alone in the second and third patient. None of the patients showed immediate reactions to skin tests, while positive intradermal reactions after 24 h to amoxicillin and clindamycin were observed in the first patient, and positive intradermal reactions after 24 h to clindamycin were observed in the second and third patients.

Conclusions: Skin testing with clindamycin in the diagnosis of drug hypersensitivity carries some risk of adverse reactions. A stepwise and individual diagnostic work-up, considering potential risk factors, and testing in a specialized centre with emergency equipment available is highly recommended.
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http://dx.doi.org/10.1111/cod.12956DOI Listing
April 2018

Omalizumab treatment in patients with chronic inducible urticaria: A systematic review of published evidence.

J Allergy Clin Immunol 2018 02 24;141(2):638-649. Epub 2017 Jul 24.

Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Berlin, Germany.

Background: Omalizumab, a recombinant anti-IgE antibody, effectively treats chronic spontaneous urticaria. Evidence is lacking in patients with chronic inducible urticarias (CIndUs), which are frequently H-antihistamine resistant.

Objective: From the current published literature, we aimed to determine the strength of evidence for omalizumab efficacy and safety in the treatment of CIndUs.

Methods: We performed a PubMed search to identify evidence on omalizumab use in the following 9 CIndU subtypes: symptomatic dermographism, cold urticaria, delayed-pressure urticaria, solar urticaria, heat urticaria, vibratory angioedema, cholinergic urticaria, contact urticaria, and aquagenic urticaria.

Results: Forty-three trials, case studies, case reports, and analyses were identified. Our review indicates that omalizumab has substantial benefits in patients with various CIndUs. The evidence is strongest for symptomatic dermographism, cold urticaria, and solar urticaria. Little/no evidence was available on vibratory angioedema and aquagenic and contact urticaria. Our review supports rapid onset of action demonstrated through early symptom control in most cases, sometimes within 24 hours. Many patients gained complete/partial symptom relief and substantially improved quality of life. Adverse events were generally low, with omalizumab being well tolerated by most patients, including children.

Conclusions: A strong body of evidence supports the use of omalizumab in the treatment of patients with therapy-refractory CIndU. More data from randomized controlled studies are warranted.
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http://dx.doi.org/10.1016/j.jaci.2017.06.032DOI Listing
February 2018

[Christmas from an allergist's perspective].

Authors:
Bettina Wedi

Dtsch Med Wochenschr 2016 Dec 14;141(25):1828-1834. Epub 2016 Dec 14.

The customs and traditions associated with Christmas may result in allergic reactions to allergens that are typical for this period. On the one hand the rise in prevalence of allergic diseases has continued in the industrialized world for the last decades and allergies are regarded as widespread diseases. On the other hand the 21th century is a time of "allergy delusion". This review summarizes the facts about allergic reactions to Christmas typical decoration, food and behavior. Taken together, allergic reactions to Christmas tree, poinsettia, Christmas cactus, perfumed candles, Christmas typical food, common gifts like mobile phones and laptops, frankincense, myrrh and pollens have been described but in very rare instances. The chance to survive Christmas without allergic symptoms is high, particularly for non-atopics.
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http://dx.doi.org/10.1055/s-0042-117370DOI Listing
December 2016

Guideline for the diagnosis of drug hypersensitivity reactions: S2K-Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) and the German Dermatological Society (DDG) in collaboration with the Association of German Allergologists (AeDA), the German Society for Pediatric Allergology and Environmental Medicine (GPA), the German Contact Dermatitis Research Group (DKG), the Swiss Society for Allergy and Immunology (SGAI), the Austrian Society for Allergology and Immunology (ÖGAI), the German Academy of Allergology and Environmental Medicine (DAAU), the German Center for Documentation of Severe Skin Reactions and the German Federal Institute for Drugs and Medical Products (BfArM).

Allergo J Int 2015;24(3):94-105

Department of Dermatology and Allergology, RTWH Aachen, Aachen, Germany.

Drug hypersensitivity reactions are unpredictable adverse drug reactions. They manifest either within 1-6 h following drug intake (immediate reactions) with mild to life-threatening symptoms of anaphylaxis, or several hours to days later (delayed reactions), primarily as exanthematous eruptions. It is not always possible to detect involvement of the immune system (allergy). Waiving diagnostic tests can result in severe reactions on renewed exposure on the one hand, and to unjustified treatment restrictions on the other. With this guideline, experts from various specialist societies and institutions have formulated recommendations and an algorithm for the diagnosis of allergies. The key principles of diagnosing allergic/hypersensitivity drug reactions are presented. Where possible, the objective is to perform allergy diagnostics within 4 weeks-6 months following the reaction. A clinical classification of symptoms based on the morphology and time course of the reaction is required in order to plan a diagnostic work-up. In the case of typical symptoms of a drug hypersensitivity reaction and unequivocal findings from validated skin and/or laboratory tests, a reaction can be attributed to a trigger with sufficient confidence. However, skin and laboratory tests are often negative or insufficiently reliable. In such cases, controlled provocation testing is required to clarify drug reactions. This method is reliable and safe when attention is paid to indications and contraindications and performed under appropriate medical supervision. The results of the overall assessment are discussed with the patient and documented in an "allergy passport" in order to ensure targeted avoidance in the future and allow the use of alternative drugs where possible.
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http://dx.doi.org/10.1007/s40629-015-0052-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4479479PMC
January 2015

Urticaria.

J Dtsch Dermatol Ges 2014 Nov 1;12(11):997-1007; quiz 1008-9. Epub 2014 Oct 1.

Department for Dermatology, Allergology, and Venereology, Hannover Medical School, Germany.

Urticaria is a very common skin disease which was already described in the ancient world. Questions still remain about its pathogenesis and management remain open. Compared to other common skin diseases, the published evidence is rather low. The clinical symptoms with pruritic transient wheals and/or angioedema are caused by mediators (particularly histamine) released by activated mast cells and basophils. The mechanism of target cell activation has not been clarified in detail for most urticaria subtypes. Different urticaria subtypes should be distinguished. Spontaneous forms are more common than inducible forms. Chronic urticaria and urticaria in certain age groups (children, pregnancy) can be difficult to manage. Therefore, international consensus resulting in the regular update of urticaria guidelines can be very helpful. Currently, these updated guidelines include a three-step treatment algorithm for chronic spontaneous urticaria. Only the first step of this algorithm, second generation H1-antihistamine in standard dose, utilized approved drugs. However after omalizumab was established as a third line choice in the guideline algorithm, it has approved in many countries for chronic spontaneous urticaria without response to H1-antihistamines. The exact mechanism of action of omalizumab in urticaria has not been fully elucidated. Unrevealing this mechanism might result in a deeper understanding of urticaria pathogenesis and the development of further therapeutic strategies.
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http://dx.doi.org/10.1111/ddg.12441DOI Listing
November 2014

Guideline on allergen-specific immunotherapy in IgE-mediated allergic diseases: S2k Guideline of the German Society for Allergology and Clinical Immunology (DGAKI), the Society for Pediatric Allergy and Environmental Medicine (GPA), the Medical Association of German Allergologists (AeDA), the Austrian Society for Allergy and Immunology (ÖGAI), the Swiss Society for Allergy and Immunology (SGAI), the German Society of Dermatology (DDG), the German Society of Oto- Rhino-Laryngology, Head and Neck Surgery (DGHNO-KHC), the German Society of Pediatrics and Adolescent Medicine (DGKJ), the Society for Pediatric Pneumology (GPP), the German Respiratory Society (DGP), the German Association of ENT Surgeons (BV-HNO), the Professional Federation of Paediatricians and Youth Doctors (BVKJ), the Federal Association of Pulmonologists (BDP) and the German Dermatologists Association (BVDD).

Allergo J Int 2014;23(8):282-319

German Allergy and Asthma Association, Mönchengladbach, Germany.

The present guideline (S2k) on allergen-specific immunotherapy (AIT) was established by the German, Austrian and Swiss professional associations for allergy in consensus with the scientific specialist societies and professional associations in the fields of otolaryngology, dermatology and venereology, pediatric and adolescent medicine, pneumology as well as a German patient organization (German Allergy and Asthma Association; Deutscher Allergie- und Asthmabund, DAAB) according to the criteria of the Association of the Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF). AIT is a therapy with disease-modifying effects. By administering allergen extracts, specific blocking antibodies, toler-ance-inducing cells and mediators are activated. These prevent further exacerbation of the allergen-triggered immune response, block the specific immune response and attenuate the inflammatory response in tissue. Products for SCIT or SLIT cannot be compared at present due to their heterogeneous composition, nor can allergen concentrations given by different manufacturers be compared meaningfully due to the varying methods used to measure their active ingredients. Non-modified allergens are used for SCIT in the form of aqueous or physically adsorbed (depot) extracts, as well as chemically modified allergens (allergoids) as depot extracts. Allergen extracts for SLIT are used in the form of aqueous solutions or tablets. The clinical efficacy of AIT is measured using various scores as primary and secondary study endpoints. The EMA stipulates combined symptom and medication scores as primary endpoint. A harmonization of clinical endpoints, e. g., by using the combined symptom and medication scores (CSMS) recommended by the EAACI, is desirable in the future in order to permit the comparison of results from different studies. The current CONSORT recommendations from the ARIA/GA2LEN group specify standards for the evaluation, presentation and publication of study results. According to the Therapy allergen ordinance (TAV), preparations containing common allergen sources (pollen from grasses, birch, alder, hazel, house dust mites, as well as bee and wasp venom) need a marketing authorization in Germany. During the marketing authorization process, these preparations are examined regarding quality, safety and efficacy. In the opinion of the authors, authorized allergen preparations with documented efficacy and safety, or preparations tradeable under the TAV for which efficacy and safety have already been documented in clinical trials meeting WAO or EMA standards, should be preferentially used. Individual formulations (NPP) enable the prescription of rare allergen sources (e.g., pollen from ash, mugwort or ambrosia, mold Alternaria, animal allergens) for specific immunotherapy. Mixing these allergens with TAV allergens is not permitted. Allergic rhinitis and its associated co-morbidities (e. g., bronchial asthma) generate substantial direct and indirect costs. Treatment options, in particular AIT, are therefore evaluated using cost-benefit and cost-effectiveness analyses. From a long-term perspective, AIT is considered to be significantly more cost effective in allergic rhinitis and allergic asthma than pharmacotherapy, but is heavily dependent on patient compliance. Meta-analyses provide unequivocal evidence of the efficacy of SCIT and SLIT for certain allergen sources and age groups. Data from controlled studies differ in terms of scope, quality and dosing regimens and require product-specific evaluation. Therefore, evaluating individual preparations according to clearly defined criteria is recommended. A broad transfer of the efficacy of certain preparations to all preparations administered in the same way is not endorsed. The website of the German Society for Allergology and Clinical Immunology (www.dgaki.de/leitlinien/s2k-leitlinie-sit; DGAKI: Deutsche Gesellschaft für Allergologie und klinische Immunologie) provides tables with specific information on available products for AIT in Germany, Switzerland and Austria. The tables contain the number of clinical studies per product in adults and children, the year of market authorization, underlying scoring systems, number of randomized and analyzed subjects and the method of evaluation (ITT, FAS, PP), separately given for grass pollen, birch pollen and house dust mite allergens, and the status of approval for the conduct of clinical studies with these products. Strong evidence of the efficacy of SCIT in pollen allergy-induced allergic rhinoconjunctivitis in adulthood is well-documented in numerous trials and, in childhood and adolescence, in a few trials. Efficacy in house dust mite allergy is documented by a number of controlled trials in adults and few controlled trials in children. Only a few controlled trials, independent of age, are available for mold allergy (in particular Alternaria). With regard to animal dander allergies (primarily to cat allergens), only small studies, some with methodological deficiencies are available. Only a moderate and inconsistent therapeutic effect in atopic dermatitis has been observed in the quite heterogeneous studies conducted to date. SCIT has been well investigated for individual preparations in controlled bronchial asthma as defined by the Global Initiative for Asthma (GINA) 2007 and intermittent and mild persistent asthma (GINA 2005) and it is recommended as a treatment option, in addition to allergen avoidance and pharmacotherapy, provided there is a clear causal link between respiratory symptoms and the relevant allergen. The efficacy of SLIT in grass pollen-induced allergic rhinoconjunctivitis is extensively documented in adults and children, whilst its efficacy in tree pollen allergy has only been shown in adults. New controlled trials (some with high patient numbers) on house dust mite allergy provide evidence of efficacy of SLIT in adults. Compared with allergic rhinoconjunctivitis, there are only few studies on the efficacy of SLIT in allergic asthma. In this context, newer studies show an efficacy for SLIT on asthma symptoms in the subgroup of grass pollen allergic children, adolescents and adults with asthma and efficacy in primary house dust mite allergy-induced asthma in adolescents aged from 14 years and in adults. Aspects of secondary prevention, in particular the reduction of new sensitizations and reduced asthma risk, are important rationales for choosing to initiate treatment early in childhood and adolescence. In this context, those products for which the appropriate effects have been demonstrated should be considered. SCIT or SLIT with pollen or mite allergens can be performed in patients with allergic rhinoconjunctivitis using allergen extracts that have been proven to be effective in at least one double-blind placebo-controlled (DBPC) study. At present, clinical trials are underway for the indication in asthma due to house dust mite allergy, some of the results of which have already been published, whilst others are still awaited (see the DGAKI table "Approved/potentially completed studies" via www.dgaki.de/Leitlinien/s2k-Leitlinie-sit (according to www.clinicaltrialsregister.eu)). When establishing the indication for AIT, factors that favour clinical efficacy should be taken into consideration. Differences between SCIT and SLIT are to be considered primarily in terms of contraindications. In individual cases, AIT may be justifiably indicated despite the presence of contraindications. SCIT injections and the initiation of SLIT are performed by a physician experienced in this type of treatment and who is able to administer emergency treatment in the case of an allergic reaction. Patients must be fully informed about the procedure and risks of possible adverse events, and the details of this process must be documented (see "Treatment information sheet"; available as a handout via www.dgaki.de/Leitlinien/s2k-Leitlinie-sit). Treatment should be performed according to the manufacturer's product information leaflet. In cases where AIT is to be performed or continued by a different physician to the one who established the indication, close cooperation is required in order to ensure that treatment is implemented consistently and at low risk. In general, it is recommended that SCIT and SLIT should only be performed using preparations for which adequate proof of efficacy is available from clinical trials. Treatment adherence among AIT patients is lower than assumed by physicians, irrespective of the form of administration. Clearly, adherence is of vital importance for treatment success. Improving AIT adherence is one of the most important future goals, in order to ensure efficacy of the therapy. Severe, potentially life-threatening systemic reactions during SCIT are possible, but - providing all safety measures are adhered to - these events are very rare. Most adverse events are mild to moderate and can be treated well. Dose-dependent adverse local reactions occur frequently in the mouth and throat in SLIT. Systemic reactions have been described in SLIT, but are seen far less often than with SCIT. In terms of anaphylaxis and other severe systemic reactions, SLIT has a better safety profile than SCIT. The risk and effects of adverse systemic reactions in the setting of AIT can be effectively reduced by training of personnel, adhering to safety standards and prompt use of emergency measures, including early administration of i. m. epinephrine. Details on the acute management of anaphylactic reactions can be found in the current S2 guideline on anaphylaxis issued by the AWMF (S2-AWMF-LL Registry Number 061-025). AIT is undergoing some innovative developments in many areas (e. g., allergen characterization, new administration routes, adjuvants, faster and safer dose escalation protocols), some of which are already being investigated in clinical trials. Pfaar O, Bachert C, Bufe A, Buhl R, Ebner C, Eng P, Friedrichs F, Fuchs T, Hamelmann E, Hartwig-Bade D, Hering T, Huttegger I, Jung K, Klimek L, Kopp MV, Merk H, Rabe U, Saloga J, Schmid-Grendelmeier P, Schuster A, Schwerk N, Sitter H, Umpfenbach U, Wedi B, Wöhrl S, Worm M, Kleine-Tebbe J. Guideline on allergen-specific immunotherapy in IgE-mediated allergic diseases - S2k Guideline of the German Society for Allergology and Clinical Immunology (DGAKI), the Society for Pediatric Allergy and Environmental Medicine (GPA), the Medical Association of German Allergologists (AeDA), the Austrian Society for Allergy and Immunology (ÖGAI), the Swiss Society for Allergy and Immunology (SGAI), the German Society of Dermatology (DDG), the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery (DGHNO-KHC), the German Society of Pediatrics and Adolescent Medicine (DGKJ), the Society for Pediatric Pneumology (GPP), the German Respiratory Society (DGP), the German Association of ENT Surgeons (BV-HNO), the Professional Federation of Paediatricians and Youth Doctors (BVKJ), the Federal Association of Pulmonologists (BDP) and the German Dermatologists Association (BVDD). Allergo J Int 2014;23:282-319.
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http://dx.doi.org/10.1007/s40629-014-0032-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4479478PMC
January 2014

Management of childhood urticaria: current knowledge and practical recommendations.

Acta Derm Venereol 2013 Sep;93(5):500-8

Department of Immunoallergy, Hospital Dona Estefania, Centro Hospitalar Lisboa Central Rua Jacinta Marto, Lisbon, Portugal.

Urticaria, defined by the presence of wheals and/or angio-edema, is a common condition in children, prompting parents to consult physicians. For its successful management, paediatric-specific features must be taken into account, regarding the identification of eliciting triggers and pharmacological therapy. This review systematically discusses the current best-available evidence on spontaneous acute and chronic urticaria as well as physical and other urticaria types in children. Potential underlying causes, namely infections, food and drug hypersensitivity, autoreactivity and autoimmune or other conditions, and eliciting stimuli are considered, with practical recommendations for specific diagnostic approaches. Second-generation antihistamines are the mainstay of pharmacological treatment aimed at relief of symptoms, which require dose adjustment for pae-diatric use. Other therapeutic interventions are also discussed. In addition, unmet needs are highlighted, aiming to promote research into the paediatric population, ultimately aiming at the effective management of childhood urticaria.
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http://dx.doi.org/10.2340/00015555-1573DOI Listing
September 2013