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BACKGROUND: Approximately 10% of European children are classified as allergic to drugs. In the majority of these children, no allergy to ß-lactam antibiotics (BLA) can be found. In most cases, the exanthema is caused by the infection. MATERIALS AND METHODS: The objective of this paper is to describe the causes and consequences of a misdiagnosis of drug allergy. We propose a method for establishing a correct diagnosis in the case of a history of a delayed reaction during treatment with a BLA. For this purpose, a proposal was discussed via e-mail communication, and consensus was reached among the members of the drug allergy working groups of the participating medical societies. RESULTS: The suspicion of a BLA allergy based on the medical history alone can have a negative impact on future antibiotic treatment. Exanthema associated with febrile infections not related to drug administration is a frequent finding in children. This makes it all the more important to be able to recommend a standardized procedure for clarification in children and adolescents with suspected hypersensitivity reactions. The medical history should be the basis on which to diagnose either a drug allergy or another possible differential diagnosis. A mild maculopapular exanthema (MPE) can be an expression of a drug allergy or a nonspecific viral exanthema. Uncomplicated MPE is not associated with significant systemic involvement, and there is no involvement of the mucous membranes or cutaneous blistering. Only a small number of children with uncomplicated MPE show positive skin tests and only ~ 7 - 16% of suspected BLA diagnoses can be confirmed by provocation tests. Thus, in children with uncomplicated MPE, drug provocation can be performed in an outpatient setting even without prior skin testing. This paper presents a 3-day outpatient direct provocation scheme for BLA delabeling in children with uncomplicated MPE. CONCLUSION: Many children and adolescents are unnecessarily denied treatment with BLA after an uncomplicated MPE while being treated with a BLA.
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BACKGROUND: Clinical trials investigating drugs for the acute treatment of hereditary angioedema attacks have assessed many different outcomes. This heterogeneity limits the comparability of trial results and may lead to selective outcome reporting bias and a high burden on trial participants. OBJECTIVE: To achieve consensus on a core outcome set composed of key outcomes that ideally should be used in all clinical efficacy trials involving the acute treatment of hereditary angioedema attacks. METHODS: We conducted a Delphi consensus study involving all relevant parties: patients with hereditary angioedema, hereditary angioedema expert clinicians and clinical researchers, pharmaceutical companies, and regulatory bodies. Two Internet-based survey rounds were conducted. In round 1, panelists indicated the importance of individual outcomes used in clinical trials on a 9-point Likert scale. Based on these results, a core outcome set was developed and voted on by panelists in round 2. RESULTS: A total of 58 worldwide panelists completed both rounds. The first round demonstrated high importance scores and substantial agreement among the panelists. In the second round, a consensus of 90% or greater was achieved on a core outcome set consisting of five key outcomes: change in overall symptom severity at one predetermined time point between 15 minutes and 4 hours after treatment, time to end of progression of all symptoms, the need for rescue medication during the entire attack, impairment of daily activities, and treatment satisfaction. CONCLUSIONS: This international study obtained a high level of consensus on a core outcome set for the acute treatment of hereditary angioedema attacks, consisting of five key outcomes.
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Angioedemas Hereditários , Humanos , Angioedemas Hereditários/tratamento farmacológico , Resultado do Tratamento , Técnica Delphi , Inquéritos e Questionários , Ensaios Clínicos como Assunto , Consenso , Feminino , Avaliação de Resultados em Cuidados de SaúdeRESUMO
BACKGROUND: Angioedema (AE) manifests with intermittent, localized, self-limiting swelling of the subcutaneous and/or submucosal tissue. AE is heterogeneous, can be hereditary or acquired, may occur only once or be recurrent, may exhibit wheals or not, and may be due to mast cell mediators, bradykinin, or other mechanisms. Several different taxonomic systems are currently used, making it difficult to compare the results of studies, develop multicenter collaboration, and harmonize AE treatment. OBJECTIVE: We developed a consensus on the definition, acronyms, nomenclature, and classification of AE (DANCE). METHODS: The initiative involved 91 experts from 35 countries and was endorsed by 53 scientific and medical societies, and patient organizations. A consensus was reached by online discussion and voting using the Delphi process over a period of 16 months (June 2021 to November 2022). RESULTS: The DANCE initiative resulted in an international consensus on the definition, classification, and terminology of AE. The new consensus classification features 5 types and endotypes of AE and a harmonized vocabulary of abbreviations/acronyms. CONCLUSION: The DANCE classification complements current clinical guidelines and expert consensus recommendations on the diagnostic assessment and treatment of AE. DANCE does not replace current clinical guidelines, and expert consensus algorithms and should not be misconstrued in a way that affects reimbursement of medicines prescribed by physicians using sound clinical judgment. We anticipate that this new AE taxonomy and nomenclature will harmonize and facilitate AE research and clinical studies, thereby improving patient care.
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Angioedema , Consenso , Terminologia como Assunto , Humanos , Angioedema/classificação , Angioedema/diagnóstico , Abreviaturas como Assunto , Técnica DelphiRESUMO
This S3 guideline was created based on the European S3 guideline, with special consideration of the medical conditions in the German-speaking region and incorporating additions from the previous German-language version. The interdisciplinary guideline commission consisted of representatives from the German Dermatological Society, the Professional Association of German Dermatologists, the Austrian Society of Dermatology and Venereology, the Swiss Society of Dermatology and Venereology, the German Society for Allergology and Clinical Immunology, the German Society for Pediatric and Adolescent Medicine, the Professional Association of Pediatricians and Adolescent Medicine, the Society for Pediatric Allergology and Environmental Medicine, the German Society for Pediatric Rehabilitation and Prevention, the German Society for Psychosomatic Medicine and Medical Psychotherapy, the German Network for Health Services Research, the German Eczema Association and the German Allergy and Asthma Association. This first part of the guideline focuses on the definition and diagnostic aspects of atopic dermatitis (AD), addressing topical therapy as well as non-pharmacological treatment approaches such as UV therapy, psychoeducational therapy, dietary interventions for AD, allergen immunotherapy for AD, and complementary medicine. This part of the guideline also covers specific aspects of AD in children and adolescents, during pregnancy and lactation, and in the context of family planning. Additionally, it addresses occupational aspects of AD and highlights the perspective of the patients. The second part of the guideline, published separately, addresses the systemic therapy of AD.
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Asma , Dermatite Atópica , Adolescente , Feminino , Gravidez , Humanos , Criança , Dermatite Atópica/terapia , Dermatite Atópica/tratamento farmacológicoRESUMO
The present S3 guideline was created based on the European English-language S3 guideline, with special consideration given to the medical conditions in the German-speaking region, and with additions from the previous German-language version, in accordance with the criteria of the AWMF. This second part of the guideline addresses the systemic therapy of atopic dermatitis (AD). It covers topics such as the indication for systemic therapy in children, adolescents, and adult patients with AD. Furthermore, it addresses all medications approved for AD, such as the biologics dupilumab and tralokinumab, the Janus kinase inhibitors abrocitinib, baricitinib, and upadacitinib, as well as conventional immunosuppressive therapies with systemic glucocorticosteroids and ciclosporin. Additionally, it discusses systemic off-label therapies. The first part of the guideline, published separately, includes the definition and diagnostic aspects of AD, describes topical therapy, non-drug therapy approaches, and addresses aspects related to special patient groups.
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Produtos Biológicos , Dermatite Atópica , Adolescente , Adulto , Criança , Humanos , Dermatite Atópica/diagnóstico , Dermatite Atópica/tratamento farmacológico , Administração Cutânea , Ciclosporina , Terapia de Imunossupressão , Resultado do TratamentoRESUMO
Hereditary angioedema (HAE) is a rare, painful, disabling and potentially fatal disease, where early diagnosis and effective treatment are critical. These Austrian guidelines for the diagnosis and management of HAE provide instructions and advice on the state of the art management of HAE in Austria in contrast to global guidelines, where the situation of all countries worldwide must be taken into account. Our goal is to help Austrian physicians to consider HAE as a differential diagnosis with corresponding symptoms, to make rational decisions for the diagnosis and management of HAE with C1-inhibitor deficiency (type 1 or type 2). The guidelines provide information on common and important clinical symptoms, diagnostic methods, treatment modalities, available HAE-specific medications in Austria and last but not least to motivate physicians to refer patients to HAE centers for confirmation of the diagnosis and adequate treatment decisions.
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Angioedemas Hereditários , Humanos , Angioedemas Hereditários/terapia , Angioedemas Hereditários/tratamento farmacológico , Diagnóstico Diferencial , Resultado do Tratamento , Dor , Gerenciamento ClínicoRESUMO
BACKGROUND: The specificity of extract-based pollen allergy diagnosis is decreased due to cross-reactivity via cross-reactive carbohydrate determinants (CCDs) or panallergens such as profilins or polcalcins. This study aimed to explore the prevalence of sensitization to seasonal extracts, CCDs, profilin and polcalcin and investigate the sensitivity and specificity of seasonal molecular allergy diagnosis (MAD) using commercially available test methods. METHODS: 2948 patients were screened for specific immunoglobulin E to ash, birch, mugwort, ragweed and timothy grass pollen extracts and grouped according to the number of positive tests (1-5). 100 patients from each group and a control group were randomly selected to calculate the prevalence of CCD and panallergen sensitization. With 742 patients, sensitivity and specificity of MAD (Alt a 1, Fra/Ole e 1, Bet v 1, Phl p 1, Art v 1, and Amb a 1) was determined. RESULTS: 1627 patients (55.2%) were positive to at least one, and 1002 patients (34.0%) were positive to multiple of the five pollen allergens investigated; 18.5% of the pollen-sensitized patients had sensitization to CCDs or panallergens. Specifically, sensitization to CCDs, profilins, and polcalcins was observed in 8.7%, 10.9%, and 2.9% of these patients, respectively. The sensitivity of MAD was high, with sensitivities between 96.2% and 100% using ImmunoCAP and 91.5% and 100% using ALEX2 . Specificity was 100% for both assays. CONCLUSIONS: Due to cross-reactivity, about one-fifth of pollen-sensitized patients is at risk of misdiagnosis. However, MAD is sensitive, specific and helps to avoid misdiagnosis and select primary allergen sources for immunotherapy.
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In patients with hereditary angioedema (HAE), bradykinin causes swelling episodes by activating bradykinin B2 receptors. Icatibant, a selective bradykinin B2 receptor antagonist, is approved for on-demand treatment of HAE attacks. The Icatibant Outcome Survey (IOS; NCT01034969) is an ongoing observational registry initiated in 2009 to monitor the effectiveness/safety of icatibant in routine clinical practice. As of March 2019, 549 patients with HAE type 1 or 2 from the IOS registry had been treated of 5995 total attacks. This article reviews data published from IOS over time which have demonstrated that the effectiveness of icatibant in a real-world setting is comparable to efficacy in clinical trials; one dose is effective for the majority of attacks; early treatment (facilitated by self-administration) leads to faster resolution and shorter attack duration; effectiveness/safety of icatibant has been shown across a broad range of patient subgroups, including children/adolescents and patients with HAE with normal C1 inhibitor levels; and tolerability has been demonstrated in patients aged ≥65 years. Additionally, this review highlights how IOS data have provided valuable insights into patients' diagnostic journeys and treatment behaviours across individual countries. Such findings have helped to inform clinical strategies and guidelines to optimise HAE management and limit disease burden. This research was sponsored by Takeda Development Center Americas, Inc. Takeda Development Center Americas, Inc., provided funding to Excel Medical Affairs for support in writing and editing this manuscript.
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Angioedemas Hereditários , Adolescente , Angioedemas Hereditários/diagnóstico , Angioedemas Hereditários/tratamento farmacológico , Bradicinina/análogos & derivados , Bradicinina/farmacologia , Bradicinina/uso terapêutico , Antagonistas de Receptor B2 da Bradicinina/efeitos adversos , Criança , Humanos , Resultado do TratamentoRESUMO
Hereditary Angioedema (HAE) is a rare and disabling disease for which early diagnosis and effective therapy are critical. This revision and update of the global WAO/EAACI guideline on the diagnosis and management of HAE provides up-to-date guidance for the management of HAE. For this update and revision of the guideline, an international panel of experts reviewed the existing evidence, developed 28 recommendations, and established consensus by an online DELPHI process. The goal of these recommendations and guideline is to help physicians and their patients in making rational decisions in the management of HAE with deficient C1-inhibitor (type 1) and HAE with dysfunctional C1-inhibitor (type 2), by providing guidance on common and important clinical issues, such as: 1) How should HAE be diagnosed? 2) When should HAE patients receive prophylactic on top of on-demand treatment and what treatments should be used? 3) What are the goals of treatment? 4) Should HAE management be different for special HAE patient groups such as children or pregnant/breast feeding women? 5) How should HAE patients monitor their disease activity, impact, and control? It is also the intention of this guideline to help establish global standards for the management of HAE and to encourage and facilitate the use of recommended diagnostics and therapies for all patients.
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Hereditary angioedema (HAE) is a rare and disabling disease for which early diagnosis and effective therapy are critical. This revision and update of the global WAO/EAACI guideline on the diagnosis and management of HAE provides up-to-date guidance for the management of HAE. For this update and revision of the guideline, an international panel of experts reviewed the existing evidence, developed 28 recommendations, and established consensus by an online DELPHI process. The goal of these recommendations and guideline is to help physicians and their patients in making rational decisions in the management of HAE with deficient C1 inhibitor (type 1) and HAE with dysfunctional C1 inhibitor (type 2), by providing guidance on common and important clinical issues, such as: (1) How should HAE be diagnosed? (2) When should HAE patients receive prophylactic on top of on-demand treatment and what treatments should be used? (3) What are the goals of treatment? (4) Should HAE management be different for special HAE patient groups such as children or pregnant/breast-feeding women? and (5) How should HAE patients monitor their disease activity, impact, and control? It is also the intention of this guideline to help establish global standards for the management of HAE and to encourage and facilitate the use of recommended diagnostics and therapies for all patients.
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Angioedemas Hereditários , Angioedemas Hereditários/prevenção & controle , Angioedemas Hereditários/terapia , Criança , Proteína Inibidora do Complemento C1/genética , Proteína Inibidora do Complemento C1/uso terapêutico , Consenso , Feminino , Humanos , GravidezRESUMO
BACKGROUND: Food anaphylaxis is commonly elicited by unintentional ingestion of foods containing the allergen above the tolerance threshold level of the individual. While labeling the 14 main allergens used as ingredients in food products is mandatory in the EU, there is no legal definition of declaring potential contaminants. Precautionary allergen labeling such as "may contain traces of" is often used. However, this is unsatisfactory for consumers as they get no information if the contamination is below their personal threshold. In discussions with the food industry and technologists, it was suggested to use a voluntary declaration indicating that all declared contaminants are below a threshold of 0.5 mg protein per 100 g of food. This concentration is known to be below the threshold of most patients, and it can be technically guaranteed in most food production. However, it was also important to assess that in case of accidental ingestion of contaminants below this threshold by highly allergic patients, no fatal anaphylactic reaction could occur. Therefore, we performed a systematic review to assess whether a fatal reaction to 5mg of protein or less has been reported, assuming that a maximum portion size of 1kg of a processed food exceeds any meal and thus gives a sufficient safety margin. METHODS: MEDLINE and EMBASE were searched until 24 January 2021 for provocation studies and case reports in which one of the 14 major food allergens was reported to elicit fatal or life-threatening anaphylactic reactions and assessed if these occurred below the ingestion of 5mg of protein. A Delphi process was performed to obtain an expert consensus on the results. RESULTS: In the 210 studies included, in our search, no reports of fatal anaphylactic reactions reported below 5 mg protein ingested were identified. However, in provocation studies and case reports, severe reactions below 5 mg were reported for the following allergens: eggs, fish, lupin, milk, nuts, peanuts, soy, and sesame seeds. CONCLUSION: Based on the literature studied for this review, it can be stated that cross-contamination of the 14 major food allergens below 0.5 mg/100 g is likely not to endanger most food allergic patients when a standard portion of food is consumed. We propose to use the statement "this product contains the named allergens in the list of ingredients, it may contain traces of other contaminations (to be named, e.g. nut) at concentrations less than 0.5 mg per 100 g of this product" for a voluntary declaration on processed food packages. This level of avoidance of cross-contaminations can be achieved technically for most processed foods, and the statement would be a clear and helpful message to the consumers. However, it is clearly acknowledged that a voluntary declaration is only a first step to a legally binding solution. For this, further research on threshold levels is encouraged.
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Anafilaxia , Hipersensibilidade Alimentar , Alérgenos/análise , Anafilaxia/diagnóstico , Anafilaxia/etiologia , Anafilaxia/prevenção & controle , Animais , Ovos , Hipersensibilidade Alimentar/diagnóstico , Rotulagem de Alimentos , HumanosRESUMO
BACKGROUND: The determination of functional C1-INH is complex and depends on methodology, sample transport, and storage conditions. In clinical practice, we encounter individuals with pathological values which then cannot be proved true, and HAE patients in whom the values were wrongly found to be normal under non-optimum conditions. We aimed to test realistic real-life sample processing conditions for accurate C1-INH determination. METHODS: We conducted two national inter-laboratory comparisons with optimal sample preparation but different dispatch conditions. We also investigated variations of temperature and time, and their influence on C1-INH. RESULTS: C1-INH levels showed a significantly wider dispersion under suboptimal transport conditions than under optimal conditions (p < 0.00001). Two putatively healthy patient samples turned out to be pathological. Contrary to our expectations, we found no significant trend in a specific direction when the variables of temperature, time and sample material were combined and varied under realistic conditions. However, the range of variation in [%] functionality was markedly greater in supposedly healthy volunteers. Thus, under experimental conditions we obtained false pathological results that were not far from reality. CONCLUSION: C1- INH determination is crucial for the diagnosis of HAE. Time, temperature, and sample handling have a significant impact on this laboratory value, sometimes leading to incorrect values, inaccurate diagnoses, and inappropriate therapies. This underlines the importance of proper handling of samples. If a patient has ambiguous C1-INH values despite optimized conditions, thus hindering a conclusive diagnosis of HAE, we recommend genetic testing.
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Angioedemas Hereditários/diagnóstico , Proteína Inibidora do Complemento C1/análise , Técnicas Imunológicas , Manejo de Espécimes , Angioedemas Hereditários/sangue , Angioedemas Hereditários/imunologia , Biomarcadores/sangue , Estudos de Casos e Controles , Centrifugação , Humanos , Ensaio de Proficiência Laboratorial , Variações Dependentes do Observador , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Temperatura , Fatores de TempoAssuntos
Complicações Infecciosas na Gravidez , Sífilis , Antibacterianos/uso terapêutico , Feminino , Humanos , Penicilinas/uso terapêutico , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Sistema de Registros , Sífilis/diagnóstico , Sífilis/tratamento farmacológicoRESUMO
BACKGROUND: There is controversy whether taking ß-blockers or ACE inhibitors (ACEI) is a risk factor for more severe systemic insect sting reactions (SSR) and whether it increases the number or severity of adverse events (AE) during venom immunotherapy (VIT). METHODS: In this open, prospective, observational, multicenter trial, we recruited patients with a history of a SSR and indication for VIT. The primary objective of this study was to evaluate whether patients taking ß-blockers or ACEI show more systemic AE during VIT compared to patients without such treatment. RESULTS: In total, 1,425 patients were enrolled and VIT was performed in 1,342 patients. Of all patients included, 388 (27.2%) took antihypertensive (AHT) drugs (10.4% took ß-blockers, 11.9% ACEI, 5.0% ß-blockers and ACEI). Only 5.6% of patients under AHT treatment experienced systemic AE during VIT as compared with 7.4% of patients without these drugs (OR: 0.74, 95% CI: 0.43-1.22, p = 0.25). The severity of the initial sting reaction was not affected by the intake of ß-blockers or ACEI (OR: 1.14, 95% CI: 0.89-1.46, p = 0.29). In total, 210 (17.7%) patients were re-stung during VIT and 191 (91.0%) tolerated the sting without systemic symptoms. Of the 19 patients with VIT treatment failure, 4 took ß-blockers, none an ACEI. CONCLUSIONS: This trial provides robust evidence that taking ß-blockers or ACEI does neither increase the frequency of systemic AE during VIT nor aggravate SSR. Moreover, results suggest that these drugs do not impair effectiveness of VIT. (Funded by Medical University of Graz, Austria; Clinicaltrials.gov number, NCT04269629).