Publications by authors named "Franziska Ruëff"

69 Publications

Patch-test results in patients with suspected contact allergy to shoes: Retrospective IVDK data analysis 2009-2018.

Contact Dermatitis 2021 Apr 21. Epub 2021 Apr 21.

Information Network of Departments of Dermatology, University Medical Centre Göttingen, Göttingen, Germany.

Background: Allergic contact dermatitis caused by shoes is common and new relevant allergens have been identified.

Objectives: To investigate the pattern of type IV sensitization in patients with suspected allergic contact dermatitis of the feet related to shoes as a presumed culprit trigger.

Methods: Retrospective analysis of data of the Information Network of Departments of Dermatology (IVDK), 2009-2018.

Results: Six hundred twenty-five patients with presumed shoe dermatitis were identified in a cohort of 119 417 patients. Compared to patients with suspected contact sensitization from other allergen sources (n = 118 792), study group patients were more frequently sensitized to potassium dichromate (10.8% vs 3.5%), colophony (7.2% vs 3.7%), mercaptobenzothiazole (MBT; 4.0% vs 0.6%), mercapto mix (4.6% vs 0.6%), and p-tert-butylphenol formaldehyde resin (1.6% vs 0.5%). Sensitizations to urea formaldehyde resin, melamine formaldehyde resin, glutaraldehyde, tricresyl phosphate, and phenyl glycidylether were rare. Moreover, reactions to compounds in the leather or textile dyes test series were scarce.

Conclusion: A distinct sensitization pattern was observed in patients with suspected allergy to shoe materials. Although substances with low sensitization rates should be removed from the leather and shoe patch-test series, novel potential allergens should be added.
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http://dx.doi.org/10.1111/cod.13868DOI Listing
April 2021

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

Anaphylaxis in middle-aged patients.

Allergol Select 2021 23;5:133-139. Epub 2021 Mar 23.

Allergy and Immunology, Department of Dermatology, Venereology and Allergology, Charité - Universitätsmedizin Berlin, Berlin.

Age is one of the most important factors influencing the course of anaphylaxis: moreover, the frequency of elicitors of anaphylaxis is age-associated. We analyzed 8,465 anaphylactic episodes in adult patients in three age groups with a focus on patients in the middle-age group (35 - 65 years old). Insect venom was the most frequent trigger in this age group (51.2%) followed by drugs (22.8%) and food (17.3%). Severe reactions were observed in 40.1% of middle-aged patients and occurred more frequently in this age group than in patients below 35 years (27.6%) and less frequently than in patients over 65 years (55.6%). The symptoms and comorbidity profile also changed with age, most significantly regarding the increase in rates of concomitant cardiologic diseases and (severe) cardiovascular symptoms.
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http://dx.doi.org/10.5414/ALX02216EDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991893PMC
March 2021

Omalizumab ensures compatibility to bee venom immunotherapy (VIT) after VIT-induced anaphylaxis in a patient with systemic mastocytosis.

Allergol Select 2021 11;5:128-132. Epub 2021 Mar 11.

Interdisciplinary Allergy Outpatient Clinic, Department of Pneumology, University of Luebeck.

Background: Systemic reactions and anaphylaxis due to Hymenoptera venoms occur in up to 7.5% of the European population. Fatal sting reactions are very rare. Serum tryptase levels should be measured in all patients with a history of severe reactions in order to detect mastocytosis and to determine the risk of severe reactions to venom immunotherapy (VIT). The risk to experience severe or even fatal anaphylaxis due to insect stings is quite high in patients with mastocytosis. Therefore, lifelong VIT is recommended in these highly threatened patients. Multicenter studies involving a large population report that up to 20% of patients undergoing VIT have intolerance and systemic reactions to immunotherapy. Some of these side effects occur repeatedly and cannot be managed by standard treatment. A pre-treatment with the anti-IgE antibody omalizumab was useful in many cases. However, omalizumab is not approved for the indication anaphylaxis. Therefore, there is still no defined protocol for omalizumab pre-treatment, and the optimal duration, dosage as well as long-time benefits are still unclear.

Case Report: We present a 60-year-old female patient with mastocytosis who developed a severe anaphylactic reaction during initiation of bee VIT. Serum tryptase was elevated, and a KIT mutation D816V was subsequently confirmed. Component-resolved diagnostic tests revealed specific IgE antibodies to recombinant Api m 1 only. The patient was treated with 150 mg omalizumab, administered subcutaneously 5 weeks, 3 weeks, and 1 week prior to re-start of immunotherapy and for 2 months in parallel to VIT. Updosing was done by a 7-day rush schedule. During this period, no anaphylactic reaction developed, and the bee VIT was well tolerated with up to 200 µg bee venom. The patient is currently in the 3 year of treatment and tolerates the treatment very well.

Conclusion: Omalizumab may be used as a premedication in patients with mastocytosis who do not tolerate VIT. Although there is no consensus on the treatment protocol, treatment for 2 - 6 months is considered adequate. The long-term benefits of such treatment require further research.
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http://dx.doi.org/10.5414/ALX02196EDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962470PMC
March 2021

Leitlinie zu Akuttherapie und Management der Anaphylaxie - Update 2021: S2k-Leitlinie der Deutschen Gesellschaft für Allergologie und klinische Immunologie (DGAKI), des Ärzteverbands Deutscher Allergologen (AeDA), der Gesellschaft für Pädiatrische Allergologie und Umweltmedizin (GPA), der Deutschen Akademie für Allergologie und Umweltmedizin (DAAU), des Berufsverbands der Kinder- und Jugendärzte (BVKJ), der Gesellschaft für Neonatologie und Pädiatrische Intensivmedizin (GNPI), der Deutschen Dermatologischen Gesellschaft (DDG), der Österreichischen Gesellschaft für Allergologie und Immunologie (ÖGAI), der Schweizerischen Gesellschaft für Allergologie und Immunologie (SGAI), der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin (DGAI), der Deutschen Gesellschaft für Pharmakologie (DGP), der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin (DGP), der Patientenorganisation Deutscher Allergie- und Asthmabund (DAAB) und der Arbeitsgemeinschaft Anaphylaxie - Training und Edukation (AGATE).

Allergo J 2021 12;30(1):20-49. Epub 2021 Feb 12.

Klinik f. Dermatologie und Allergologie am Biederstein, Biedersteiner Str. 29, 80802 München, Germany.

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http://dx.doi.org/10.1007/s15007-020-4750-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878028PMC
February 2021

A negative breakdown test in a fragrance mix I-positive patient does not rule out contact allergy to its fragrance constituents.

Contact Dermatitis 2021 Jun 1;84(6):407-418. Epub 2021 Mar 1.

Department of Dermatology, Venereology and Allergy, University Medical Center Göttingen, Göttingen, Germany.

Background: In about half of the patients reacting positive to fragrance mix I (FM I), breakdown testing remains negative. This raises the question of whether the reaction to FM I is false-positive, or the breakdown test is false-negative.

Objectives: To identify characteristics and sensitization patterns of patients positive to FM I, but not to its fragrance constituents.

Patients And Methods: Retrospective analysis of data from the Information Network of Departments of Dermatology (IVDK) between 2005 and 2019. Three patient groups were defined according to their reaction pattern: Group I, FM I positive and ≥1 single fragrance positive in the breakdown test (n = 1912); Group II, FM I positive and breakdown test negative (n = 1318); Group III, FM I negative (n = 19 790).

Results: Regarding the pattern of concomitant reactions to other fragrances, Group II had an intermediate position between Group I and Group III. In other respects (age and sex distribution, frequency of sensitization to non-fragrance baseline series allergens), Group II rather resembled Group I.

Conclusions: Not every positive reaction to FM I in patients with negative breakdown tests is false-positive. There may be false-negative reactions to the single fragrance components when patch tested at 1% pet. Raising patch concentrations of some single fragrances is recommended.
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http://dx.doi.org/10.1111/cod.13803DOI Listing
June 2021

Guideline (S2k) on acute therapy and management of anaphylaxis: 2021 update: S2k-Guideline of the German Society for Allergology and Clinical Immunology (DGAKI), the Medical Association of German Allergologists (AeDA), the Society of Pediatric Allergology and Environmental Medicine (GPA), the German Academy of Allergology and Environmental Medicine (DAAU), the German Professional Association of Pediatricians (BVKJ), the Society for Neonatology and Pediatric Intensive Care (GNPI), the German Society of Dermatology (DDG), the Austrian Society for Allergology and Immunology (ÖGAI), the Swiss Society for Allergy and Immunology (SGAI), the German Society of Anaesthesiology and Intensive Care Medicine (DGAI), the German Society of Pharmacology (DGP), the German Respiratory Society (DGP), the patient organization German Allergy and Asthma Association (DAAB), the German Working Group of Anaphylaxis Training and Education (AGATE).

Allergo J Int 2021 28;30(1):1-25. Epub 2021 Jan 28.

Department Dermatology and Allergology Biederstein, Technical University Munich, Biedersteiner Straße 29, 80802 Munich, Germany.

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http://dx.doi.org/10.1007/s40629-020-00158-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841027PMC
January 2021

Identification and Purification of Novel Low-Molecular-Weight Lupine Allergens as Components for Personalized Diagnostics.

Nutrients 2021 Jan 28;13(2). Epub 2021 Jan 28.

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

Lupine flour is a valuable food due to its favorable nutritional properties. In spite of its allergenic potential, its use is increasing. Three lupine species, , , and . are relevant for human nutrition. The aim of this study is to clarify whether the species differ with regard to their allergen composition and whether anaphylaxis marker allergens could be identified in lupine. Patients with the following characteristics were included: lupine allergy, suspected lupine allergy, lupine sensitization only, and peanut allergy. Lupine sensitization was detected via CAP-FEIA (ImmunoCAP) and skin prick test. Protein, DNA and expressed sequence tag (EST) databases were queried for lupine proteins homologous to already known legume allergens. Different extraction methods applied on seeds from all species were examined by SDS-PAGE and screened by immunoblotting for IgE-binding proteins. The extracts underwent different and successive chromatography methods. Low-molecular-weight components were purified and investigated for IgE-reactivity. Proteomics revealed a molecular diversity of the three species, which was confirmed when investigated for IgE-reactivity. Three new allergens, profilin, and . lipid transfer protein (LTP), were identified. LTP as a potential marker allergen for severity is a valuable additional candidate for molecular allergy diagnostic tests.
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http://dx.doi.org/10.3390/nu13020409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911308PMC
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

Risk Factors and Characteristics of Biphasic Anaphylaxis.

J Allergy Clin Immunol Pract 2020 Nov - Dec;8(10):3388-3395.e6. Epub 2020 Aug 4.

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: Anaphylaxis is an immediate hypersensitivity reaction. However, a biphasic course with the second onset of symptoms can occur hours after the initial phase. Little is known about the causes of biphasic anaphylaxis making the identification of patients at risk difficult.

Objective: To identify factors predisposing for biphasic anaphylaxis for the better understanding of these reactions.

Methods: Data from the Anaphylaxis Registry (from 11 countries) including 8736 patients with monophasic and 435 biphasic anaphylaxis were analyzed.

Results: The rate of biphasic reactions in this large cohort was 4.7%. The identified risk factors were reaction severity (grade III/IV vs grade II: odds ratio [OR] = 1.34; 95% confidence interval [CI]: 1.1-1.62); multiorgan involvement; skin, gastrointestinal, severe respiratory, and cardiac symptoms; anaphylaxis caused by peanut/tree nut (OR = 1.78; 95% CI: 1.38-2.23) or an unknown elicitor (OR = 1.96; 95% CI: 1.41-2.72); exercise as a cofactor (OR = 1.44; 95% CI: 1.17-1.78); chronic urticaria as a comorbidity (OR = 2.12; 95% CI: 1.19-3.78); a prolonged interval between the contact with the elicitor and start of primary symptoms (OR for >30 vs <30 min: 1.38; 95% CI: 1.08-1.76); and antihistamine treatment (OR = 1.52; 95% CI: 1.14-2.02).

Conclusion: A biphasic course of anaphylaxis occurs more frequently in severely affected patients with multiorgan involvement. However, we identified multiple additional predictors, suggesting that the pathogenesis of biphasic reactions is more complex than being a rebound of a severe primary reaction.
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http://dx.doi.org/10.1016/j.jaip.2020.07.036DOI Listing
May 2021

Natural history and long-term follow-up of Hymenoptera allergy.

Authors:
Franziska Ruëff

Curr Opin Allergy Clin Immunol 2020 10;20(5):445-451

Department of Dermatology and Allergology, Ludwig-Maximilian University, Hospital of the University of Munich, Munich, Germany.

Purpose Of Review: Information on the natural history of hypersensitivity reactions is helpful for deciding which patient urgently needs a venom immunotherapy (VIT).

Recent Findings: The frequency of self-reported systemic allergic reactions (SAR) to Hymenoptera stings is approximately 3-7% in the Northern Hemisphere. About 25% of SAR are severe (anaphylactic shock). Fatal sting reactions are very rare. The most important risk factor for severe insect sting anaphylaxis is mast cell disease. Other risk factors are higher age, vespid venom allergy (in contrast to honeybee venom allergy), repeated stings, male sex, and treatment with ACE inhibitors. Preceding large local reactions seem not to play a risk factor for subsequent SAR.

Summary: The majority of risk factors for severe anaphylaxis are not modifiable. For patients presenting with well defined risk factors for a very severe or even fatal anaphylaxis, VIT is of utmost importance, and they should be performed for the rest of their life. Sting challenge tests are required to identify patients in whom treatment was ineffective. Those patients, who did not receive VIT although presenting with a firm indication, or in whom VIT was stopped, require yearly monitoring to teach preventive measures and to renew the emergency kit.
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http://dx.doi.org/10.1097/ACI.0000000000000671DOI Listing
October 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

Isobornyl acrylate contained in the insulin patch pump OmniPod as the cause of severe allergic contact dermatitis.

Contact Dermatitis 2018 Sep 15;79(3):178-180. Epub 2018 May 15.

Dermatologie Feldafing, Feldafing, Germany.

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http://dx.doi.org/10.1111/cod.13017DOI Listing
September 2018

Epinephrine in Severe Allergic Reactions: The European Anaphylaxis Register.

J Allergy Clin Immunol Pract 2018 Nov - Dec;6(6):1898-1906.e1. Epub 2018 Mar 30.

Department of Infectious Disease Epidemiology, Robert Koch-Institut, Berlin, Germany. Electronic address:

Background: Current guidelines recommend intramuscular administration of epinephrine as the first-line drug for the emergency treatment of severe allergic reactions (anaphylaxis), but no randomized trial evidence supports this consensus.

Objective: We aimed to assess anaphylaxis treatment practices over 10 years, covering several European regions, all allergen sources, and all age groups.

Methods: The European Anaphylaxis Register tracks elicitors, symptoms, emergency treatment, diagnostic workups, and long-term counseling for anaphylaxis incidents through web-based data entry from tertiary allergy specialists, covering information from the emergency respondent, patient, tertiary referral, and laboratory/clinical test results.

Results: We analyzed 10,184 anaphylaxis incidents. In total, 27.1% of patients treated by a health professional received epinephrine and, in total, 10.5% received a second dose. Successful administration was less frequent in German-speaking countries (minimum 19.6%) than in Greece, France, and Spain (maximum 66.7%). Over the last decade, epinephrine administration from a health professional almost doubled to reach 30.6% in 2015-2017, half of which was applied intramuscularly. A total of 14.7% of lay- or self-treated cases were treated with an autoinjector. Of those without treatment, 22.4% carried a device for administration. No change in successful administration by lay emergency respondents was found over the last 10 years. Of the reaction and patient characteristics analyzed, only clinical severity considerably influenced the likelihood of receiving epinephrine, with 66.9% of successful administrations in near-fatal (grade IV) reactions.

Conclusions: Despite clear recommendations, only a small proportion of anaphylaxis incidents are treated with epinephrine. We demonstrated a slight increase in treated patients when handled by professionals, but stagnation in lay- or self-treated anaphylaxis. The reaction circumstances, the respondent's professional background, and patient characteristics did not explain which reactions were treated.
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http://dx.doi.org/10.1016/j.jaip.2018.02.026DOI Listing
November 2019

Risk and safety requirements for diagnostic and therapeutic procedures in allergology: World Allergy Organization Statement.

World Allergy Organ J 2016 12;9(1):33. Epub 2016 Oct 12.

Universitatsklinikum GI & MR GmbH, Institut fur Laboratoriumsmedizin & Path, Standort Marburg, Marburg, Germany.

One of the major concerns in the practice of allergy is related to the safety of procedures for the diagnosis and treatment of allergic disease. Management (diagnosis and treatment) of hypersensitivity disorders involves often intentional exposure to potentially allergenic substances (during skin testing), deliberate induction in the office of allergic symptoms to offending compounds (provocation tests) or intentional application of potentially dangerous substances (allergy vaccine) to sensitized patients. These situations may be associated with a significant risk of unwanted, excessive or even dangerous reactions, which in many instances cannot be completely avoided. However, adverse reactions can be minimized or even avoided if a physician is fully aware of potential risk and is prepared to appropriately handle the situation. Information on the risk of diagnostic and therapeutic procedures in allergic diseases has been accumulated in the medical literature for decades; however, except for allergen specific immunotherapy, it has never been presented in a systematic fashion. Up to now no single document addressed the risk of the most commonly used medical procedures in the allergy office nor attempted to present general requirements necessary to assure the safety of these procedures. Following review of available literature a group of allergy experts within the World Allergy Organization (WAO), representing various continents and areas of allergy expertise, presents this report on risk associated with diagnostic and therapeutic procedures in allergology and proposes a consensus on safety requirements for performing procedures in allergy offices. Optimal safety measures including appropriate location, type and required time of supervision, availability of safety equipment, access to specialized emergency services, etc. for various procedures have been recommended. This document should be useful for allergists with already established practices and experience as well as to other specialists taking care of patients with allergies.
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http://dx.doi.org/10.1186/s40413-016-0122-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5062928PMC
October 2016

Career Advice for Young Allergy Patients.

Dtsch Arztebl Int 2016 Aug;113(31-32):519-24

Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, AllergieZENTRUM, Klinikum der Universität München, Comprehensive Pneumology Center, DZL, Deutsches Zentrum für Lungenforschung, München, Department of Pediatrics, University Hospital Carl Gustav Carus, Dresden, Department of Dermatology and Allergology, AllergieZENTRUM, Klinikum der Universität München.

Background: One-third of all young persons entering the work force have a history of atopic disease. Occupationally induced allergy and asthma generally arise in the first few months on the job, while pre-existing symptoms tend to worsen. Young persons with a history of an atopic disease should receive evidence-based advice before choosing a career.

Methods: We systematically searched PubMed for cohort studies investigating the new onset of asthma, rhinitis, or hand eczema among job trainees from before the start of training and onward into the first few years on the job. The search revealed 514 articles; we read their abstracts and selected 85 full-text articles for further analysis. 24 of these met the inclusion criteria.

Results: According to present evidence, atopy and a history of allergic disease (allergic rhinitis, atopic dermatitis) are the main risk factors for occupationally induced disease. The predictive value of a personal history of allergic diseases for the later development of an occupationally induced disease varies from 9% to 64% in the studies we analyzed. It follows that only young people with severe asthma or severe atopic eczema should be advised against choosing a job that is associated with a high risk of allergy, e.g., hairdressing or working with laboratory animals. Young people with a history of other atopic diseases should be counseled about their individual risk profile.

Conclusion: In view of the relatively poor predictive value of pre-existing atopic disease, secondary prevention is particularly important. This includes frequent medical follow-up of the course of symptoms over the first few years on the job. If sensitization or allergic symptoms arise, it should be carefully considered whether exposure reduction will enable the apprentice to stay on the job.
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http://dx.doi.org/10.3238/arztebl.2016.0519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5012160PMC
August 2016

Predominant Api m 10 sensitization as risk factor for treatment failure in honey bee venom immunotherapy.

J Allergy Clin Immunol 2016 12 24;138(6):1663-1671.e9. Epub 2016 May 24.

Department of Dermatology and Allergology, University Medical Center Gießen-Marburg, Justus Liebig University, Gießen, Germany; Allergy Research Group, Department of Dermatology, Medical Center, University of Freiburg, Freiburg, Germany. Electronic address:

Background: Component resolution recently identified distinct sensitization profiles in honey bee venom (HBV) allergy, some of which were dominated by specific IgE to Api m 3 and/or Api m 10, which have been reported to be underrepresented in therapeutic HBV preparations.

Objective: We performed a retrospective analysis of component-resolved sensitization profiles in HBV-allergic patients and association with treatment outcome.

Methods: HBV-allergic patients who had undergone controlled honey bee sting challenge after at least 6 months of HBV immunotherapy (n = 115) were included and classified as responder (n = 79) or treatment failure (n = 36) on the basis of absence or presence of systemic allergic reactions upon sting challenge. IgE reactivity to a panel of HBV allergens was analyzed in sera obtained before immunotherapy and before sting challenge.

Results: No differences were observed between responders and nonresponders regarding levels of IgE sensitization to Api m 1, Api m 2, Api m 3, and Api m 5. In contrast, Api m 10 specific IgE was moderately but significantly increased in nonresponders. Predominant Api m 10 sensitization (>50% of specific IgE to HBV) was the best discriminator (specificity, 95%; sensitivity, 25%) with an odds ratio of 8.444 (2.127-33.53; P = .0013) for treatment failure. Some but not all therapeutic HBV preparations displayed a lack of Api m 10, whereas Api m 1 and Api m 3 immunoreactivity was comparable to that of crude HBV. In line with this, significant Api m 10 sIgG induction was observed only in those patients who were treated with HBV in which Api m 10 was detectable.

Conclusions: Component-resolved sensitization profiles in HBV allergy suggest predominant IgE sensitization to Api m 10 as a risk factor for treatment failure in HBV immunotherapy.
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http://dx.doi.org/10.1016/j.jaci.2016.04.024DOI Listing
December 2016

Allergen immunotherapy for insect venom allergy: protocol for a systematic review.

Clin Transl Allergy 2015 16;6. Epub 2016 Feb 16.

Allergy and Respiratory Research Group, The University of Edinburgh, Edinburgh, UK.

Background: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines for Allergen Immunotherapy (AIT) for the Management of Insect Venom Allergy. We seek to critically assess the effectiveness, cost-effectiveness and safety of AIT in the management of insect venom allergy.

Methods: We will undertake a systematic review, which will involve searching international biomedical databases for published, in progress and unpublished evidence. Studies will be independently screened against pre-defined eligibility criteria and critically appraised using established instruments. Data will be descriptively and, if possible and appropriate, quantitatively synthesised.

Discussion: The findings from this review will be used to inform the development of recomendations for EAACI's Guidelines on AIT.
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http://dx.doi.org/10.1186/s13601-016-0095-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754882PMC
February 2016

Anaphylaxis in children and adolescents: The European Anaphylaxis Registry.

J Allergy Clin Immunol 2016 Apr 21;137(4):1128-1137.e1. Epub 2016 Jan 21.

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

Background: Anaphylaxis in children and adolescents is a potentially life-threatening condition. Its heterogeneous clinical presentation and sudden occurrence in virtually any setting without warning have impeded a comprehensive description.

Objective: We sought to characterize severe allergic reactions in terms of elicitors, symptoms, emergency treatment, and long-term management in European children and adolescents.

Methods: The European Anaphylaxis Registry recorded details of anaphylaxis after referral for in-depth diagnosis and counseling to 1 of 90 tertiary allergy centers in 10 European countries, aiming to oversample the most severe reactions. Data were retrieved from medical records by using a multilanguage online form.

Results: Between July 2007 and March 2015, anaphylaxis was identified in 1970 patients younger than 18 years. Most incidents occurred in private homes (46%) and outdoors (19%). One third of the patients had experienced anaphylaxis previously. Food items were the most frequent trigger (66%), followed by insect venom (19%). Cow's milk and hen's egg were prevalent elicitors in the first 2 years, hazelnut and cashew in preschool-aged children, and peanut at all ages. There was a continuous shift from food- to insect venom- and drug-induced anaphylaxis up to age 10 years, and there were few changes thereafter. Vomiting and cough were prevalent symptoms in the first decade of life, and subjective symptoms (nausea, throat tightness, and dizziness) were prevalent later in life. Thirty percent of cases were lay treated, of which 10% were treated with an epinephrine autoinjector. The fraction of intramuscular epinephrine in professional emergency treatment increased from 12% in 2011 to 25% in 2014. Twenty-six (1.3%) patients were either admitted to the intensive care unit or had grade IV/fatal reactions.

Conclusions: The European Anaphylaxis Registry confirmed food as the major elicitor of anaphylaxis in children, specifically hen's egg, cow's milk, and nuts. Reactions to insect venom were seen more in young adulthood. Intensive care unit admissions and grade IV/fatal reactions were rare. The registry will serve as a systematic foundation for a continuous description of this multiform condition.
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http://dx.doi.org/10.1016/j.jaci.2015.11.015DOI Listing
April 2016

Boletus dermatitis: a new variant of flagellate erythema.

Ann Allergy Asthma Immunol 2015 Sep 17;115(3):254-5. Epub 2015 Jul 17.

Department of Dermatology and Allergy, Ludwig Maximilian University, Munich, Germany. Electronic address:

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http://dx.doi.org/10.1016/j.anai.2015.06.028DOI Listing
September 2015

Ramipril and metoprolol intake aggravate human and murine anaphylaxis: evidence for direct mast cell priming.

J Allergy Clin Immunol 2015 Feb 16;135(2):491-9. Epub 2014 Oct 16.

Allergy Center Charité, CCM, Department of Dermatology and Allergology, Charité-Universitätsmedizin Berlin, Berlin, Germany. Electronic address:

Background: Cofactors contribute to the elicitation of anaphylaxis. β-Blockers and angiotensin-converting enzyme (ACE) inhibitors are widely used cardiovascular drugs. We specially designed a mouse model to further analyze the cofactor potential of these drugs.

Objective: We sought to test the hypothesis that β-blockers and ACE inhibitors alter the risk for severe anaphylaxis and to pinpoint the associated mechanism.

Methods: The risk factor potency of cardiovascular drugs on the severity of anaphylaxis in patients from German-speaking countries was analyzed. In vivo interaction of the cardiovascular drugs metoprolol (β-blocker) and ramipril (ACE inhibitor) with the anaphylactic response was determined. Mast cell (MC) mediators (histamine, serotonin, leukotriene C₄, prostaglandin D2, and mouse mast cell protease 1) were quantified in serum. Bone marrow-derived cultured MCs served to identify whether the therapeutics targeted MCs directly.

Results: Our anaphylaxis database indicated a higher risk of severe anaphylaxis after monotherapy with β-blockers or ACE inhibitors, which was more pronounced when both drugs were combined. This was confirmed in our mouse model. While single therapeutics had either no significant (ramipril) or a modestly aggravating (metoprolol) effect, their combined administration exacerbated anaphylactic symptoms potently and simultaneously enhanced MC mediators, hinting at MCs as direct targets. In fact, FcεRI-mediated MC histamine release was synergistically increased by metoprolol/ramipril or metoprolol/bradykinin (the latter increased after ACE inhibitor intake), whereas the substances had no significant effect on their own. MC priming was particularly pronounced when FcεRI aggregation was in the suboptimal range, reflecting common clinical settings.

Conclusion: β-Blockers and ACE inhibitors synergistically aggravate anaphylaxis at least partly by decreasing the threshold of MC activation.
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http://dx.doi.org/10.1016/j.jaci.2014.09.004DOI Listing
February 2015

Recombinant allergens rarely allow identification of Hymenoptera venom-allergic patients with negative specific IgE to whole venom preparations.

J Allergy Clin Immunol 2014 Aug;134(2):493-4

Department of Dermatology, Allergy Research Group, Medical Center - University of Freiburg, Freiburg, Germany. Electronic address:

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http://dx.doi.org/10.1016/j.jaci.2014.05.035DOI Listing
August 2014