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INTRODUCTION: Guidelines recommend treating asthma exacerbations (AAEs) with bronchodilators combined with inhaled and/or systemic corticosteroids. Indications for antibiotic prescriptions for AAEs are usually not incorporated although the literature shows antibiotics are frequently prescribed. AIM: To investigate the antibiotic prescription rates in AAEs and explore the possible determining factors of those practices. METHODS: A digital survey was created to determine the antibiotic prescription rates in AAEs and the influencing factors for the prescription practices. The survey was distributed among European academy of allergy and clinical immunology (EAACI) members by mass emailing and through regional/national societies in the Netherlands, Italy, Greece, and Poland. Furthermore, we retrieved local antibiotic prescription rates. RESULTS: In total, 252 participants completed the survey. Respondents stated that there is a lack of guidelines to prescribe antibiotics in AAEs. The median antibiotic prescription rate in this study was 19% [IQR: 0%-40%] and was significantly different between 4 professions: paediatrics 0% [IQR: 0%-37%], pulmonologists 25% [IQR: 10%-50%], general practitioners 25% [IQR: 0%-50%], and allergologists 17% [IQR: 0%-33%]) (p = 0.046). Additional diagnostic tests were performed in 71.4% of patients before prescription and the most common antibiotic classes prescribed were macrolides (46.0%) and penicillin (42.9%). Important clinical factors for health care providers to prescribe antibiotics were colorised/purulent sputum, abnormal lung sounds during auscultation, fever, and presence of comorbidities. CONCLUSION: In 19% of patients with AAEs, antibiotics were prescribed in various classes with a broad range among different subspecialities. This study stresses the urgency to compose evidence-based guidelines to aim for more rational antibiotic prescriptions for AAE.
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Proton pump inhibitors (PPIs) are invaluable therapeutic options in a variety of dyspeptic diseases. In addition to their well-known risk profile, PPI consumption is related to food and environmental allergies, dysbiosis, osteoporosis, as well as immediate and delayed hypersensitivity reactions (HSRs). The latter, although a rare event, around 1%-3%, due to the extraordinarily high rate of prescription and consumption of PPIs are related to a substantial risk. In this Position Paper, we provide clinicians with practical evidence-based recommendations for the diagnosis and management of HSRs to PPIs. Furthermore, the unmet needs proposed in the document aim to stimulate more in-depth investigations in the topic.
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Hipersensibilidade a Drogas , Hipersensibilidade Imediata , Hipersensibilidade , Humanos , Inibidores da Bomba de Prótons/efeitos adversos , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/etiologia , Hipersensibilidade a Drogas/terapia , Hipersensibilidade Imediata/diagnóstico , Testes CutâneosAssuntos
Hipersensibilidade a Drogas , Doenças do Sistema Imunitário , Doença do Soro , Criança , Humanos , beta-Lactamas/efeitos adversos , Doença do Soro/induzido quimicamente , Doença do Soro/diagnóstico , Antibacterianos/efeitos adversos , Testes Cutâneos , Hipersensibilidade a Drogas/diagnósticoAssuntos
Inteligência Artificial , Hipersensibilidade , Humanos , Criança , Hipersensibilidade/terapiaRESUMO
BACKGROUND: Anaphylaxis, which is rare, has been reported after COVID-19 vaccination, but its management is not standardized. METHOD: Members of the European Network for Drug Allergy and the European Academy of Allergy and Clinical Immunology interested in drug allergy participated in an online questionnaire on pre-vaccination screening and management of allergic reactions to COVID-19 vaccines, and literature was analysed. RESULTS: No death due to anaphylaxis to COVID-19 vaccines has been confirmed in scientific literature. Potential allergens, polyethylene glycol (PEG), polysorbate and tromethamine are excipients. The authors propose allergy evaluation of persons with the following histories: 1-anaphylaxis to injectable drug or vaccine containing PEG or derivatives; 2-anaphylaxis to oral/topical PEG containing products; 3-recurrent anaphylaxis of unknown cause; 4-suspected or confirmed allergy to any mRNA vaccine; and 5-confirmed allergy to PEG or derivatives. We recommend a prick-to-prick skin test with the left-over solution in the suspected vaccine vial to avoid waste. Prick test panel should include PEG 4000 or 3500, PEG 2000 and polysorbate 80. The value of in vitro test is arguable. CONCLUSIONS: These recommendations will lead to a better knowledge of the management and mechanisms involved in anaphylaxis to COVID-19 vaccines and enable more people with history of allergy to be vaccinated.
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Anafilaxia , Vacinas contra COVID-19 , COVID-19 , Hipersensibilidade a Drogas , Vacinas , Anafilaxia/diagnóstico , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/etiologia , Hipersensibilidade a Drogas/terapia , Humanos , Vacinas Sintéticas , Vacinas de mRNARESUMO
Microbiota composition and associated metabolic activities are essential for the education and development of a healthy immune system. Microbial dysbiosis, caused by risk factors such as diet, birth mode, or early infant antimicrobial therapy, is associated with the inception of allergic diseases. In turn, allergic diseases increase the risk for irrational use of antimicrobial therapy. Microbial therapies, such as probiotics, have been studied in the prevention and treatment of allergic diseases, but evidence remains limited due to studies with high heterogeneity, strain-dependent effectiveness, and variable outcome measures. In this review, we sketch the relation of microbiota with allergic diseases, the overuse and rationale for the use of antimicrobial agents in allergic diseases, and current knowledge concerning the use of bacterial products in allergic diseases. We urgently recommend 1) limiting antibiotic therapy in pregnancy and early childhood as a method contributing to the reduction of the allergy epidemic in children and 2) restricting antibiotic therapy in exacerbations and chronic treatment of allergic diseases, mainly concerning asthma and atopic dermatitis. Future research should be aimed at antibiotic stewardship implementation strategies and biomarker-guided therapy, discerning those patients that might benefit from antibiotic therapy.
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Asma , Dermatite Atópica , Hipersensibilidade , Antibacterianos/uso terapêutico , Bactérias , Criança , Pré-Escolar , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/epidemiologia , Feminino , Humanos , Hipersensibilidade/tratamento farmacológico , Hipersensibilidade/epidemiologia , Lactente , GravidezRESUMO
Allergen-specific immunotherapy (AIT) is a desensitizing treatment for allergic diseases that corrects the underlined pathological immune response to innocuous protein antigens, called allergens. Recombinant allergens employed in the AIT allowed the production of well-defined formulations that possessed consistent quality but were often less efficient than natural allergen extracts. Combining recombinant allergens with an adjuvant or immunomodulatory agent could improve AIT efficacy. This study aimed to perform structural and functional characterization of newly designed recombinant chimera composed of the Bet v 1, the major birch pollen allergen, and Banana Lectin (BanLec), TLR2, and CD14 binding protein, for the application in AIT. rBet v 1-BanLec chimera was designed in silico and expressed as a soluble fraction in Escherichia coli. Purified rBet v 1-BanLec (33.4 kDa) retained BanLec-associated biological activity of carbohydrate-binding and preserved IgE reactive epitopes of Bet v 1. The chimera revealed secondary structures with predominant ß sheets. The immunomodulatory capacity of rBet v 1-BanLec tested on macrophages showed changes in myeloperoxidase activity, reduced NO production, and significant alterations in the production of cytokines when compared to both rBanLec and rBet v 1. Comparing to rBet v 1, rBet v 1-BanLec was demonstrated to be more efficient promoter of IL-10 production as well as weaker inducer of NO production and secretion of pro-inflammatory cytokines TNFα, and IL-6. The ability of rBet v 1-BanLec to promote IL-10 in together with the preserved 3D structure of Bet v 1 part implies that the construct might exert a beneficial effect in the allergen-specific immunotherapy.
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Antígenos de Plantas/imunologia , Dessensibilização Imunológica/métodos , Interleucina-10/metabolismo , Macrófagos Peritoneais/imunologia , Musa/imunologia , Lectinas de Plantas/imunologia , Animais , Epitopos de Linfócito B/imunologia , Imunoglobulina E/imunologia , Interleucina-10/imunologia , Camundongos , Proteínas Recombinantes/imunologiaRESUMO
PURPOSE OF REVIEW: The true exanthematous reactions to drugs in children are rare and overdiagnosed. Drugs may cause exanthema either due to inducing an immune response or because of their interaction with viruses, if drugs are taken in the course of a viral infection. Also, viral infections are very often in children and they can provoke an exanthema which is difficult to differentiate from exanthematous reactions to drugs. Consequently, the majority of children are incorrectly labeled as 'allergic'. RECENT FINDINGS: The correct diagnosis of exanthematous drug reactions in children is still an important and hot topic. Most information about the approach and management of drug hypersensitivity in children is applied from available guidelines and consensus statement for adults. Recently, a systematic clinical approach for timely differential diagnosis and management of rashes in children who present a cutaneous exanthema while receiving a drug, is proposed. SUMMARY: It is important to consider the detailed clinical history of appearing and developing exanthematous drug reaction, as well as physical examination which includes the description and the distribution of exanthema and at the end making the appropriate diagnosis. Thus, it could reduce overdiagnosis and promote appropriate procedures, that will prevent the overlabeling of drug hypersensitivity in children.
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Hipersensibilidade a Drogas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Exantema , Criança , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/epidemiologia , Exantema/induzido quimicamente , Exantema/diagnóstico , Humanos , VirosesRESUMO
Beta-lactam (BL) allergy suspicion is common in children and constitutes a major public health problem, with an impact on patient's health and on medical costs. However, it has been found that most of these reactions are not confirmed by a complete allergic workup. The diagnostic value of the currently available allergy tests has been investigated intensively recently by different groups throughout the world. This has led to major changes in the management of children with a suspected BL allergy. Particularly, it is now well accepted that skin tests can be skipped before the drug provocation test in children with a benign non-immediate reaction to BL. However, there is still a debate on the optimal allergic workup to perform in children with a benign immediate reaction. In addition, management of children with severe cutaneous adverse drug reactions remains difficult. In this review, based on a selection of the most relevant studies found in the literature, we will review and discuss the diagnosis of different forms of BL allergy in children.
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Hipersensibilidade a Drogas , beta-Lactamas , Antibacterianos/efeitos adversos , Criança , Hipersensibilidade a Drogas/diagnóstico , Humanos , Testes Cutâneos , beta-Lactamas/efeitos adversosRESUMO
Older adults, especially men and/or those with diabetes, hypertension, and/or obesity, are prone to severe COVID-19. In some countries, older adults, particularly those residing in nursing homes, have been prioritized to receive COVID-19 vaccines due to high risk of death. In very rare instances, the COVID-19 vaccines can induce anaphylaxis, and the management of anaphylaxis in older people should be considered carefully. An ARIA-EAACI-EuGMS (Allergic Rhinitis and its Impact on Asthma, European Academy of Allergy and Clinical Immunology, and European Geriatric Medicine Society) Working Group has proposed some recommendations for older adults receiving the COVID-19 vaccines. Anaphylaxis to COVID-19 vaccines is extremely rare (from 1 per 100,000 to 5 per million injections). Symptoms are similar in younger and older adults but they tend to be more severe in the older patients. Adrenaline is the mainstay treatment and should be readily available. A flowchart is proposed to manage anaphylaxis in the older patients.
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Anafilaxia , COVID-19 , Idoso , Anafilaxia/etiologia , Anafilaxia/prevenção & controle , Vacinas contra COVID-19 , Epinefrina , Humanos , Masculino , SARS-CoV-2RESUMO
Childhood rashes or exanthemas are common and are usually relatively benign. There are many causes of rash in children, including mainly viruses, and less often bacterial toxins, drugs, allergens and other diseases. Viral exanthema often appears while children are taking a medication in the course of a viral infection; it can mimic drug exanthema and is perceived as a drug allergy in 10% of cases. In the vast majority of cases, the distinction between virus-induced and drug-induced skin eruption during the acute phase is not possible. The drugs most commonly implicated are beta-lactams (BL) and non-steroidal anti-inflammatory drugs (NSAIDs). Viruses, commonly Epstein-Barr virus (EBV), human herpesvirus 6 (HHV6) and cytomegalovirus (CMV), and the bacterium, Mycoplasma pneumoniae, may cause exanthema either from the infection itself (active or latent) or because of interaction with drugs that are taken simultaneously. Determination of the exact diagnosis requires a careful clinical history and thorough physical examination. Haematological and biochemical investigations and histology are not always helpful in differentiating between the two types of exanthema. Serological and polymerase chain reaction (PCR) assays can be helpful, although a concomitant acute infection does not exclude drug hypersensitivity. A drug provocation test (DPT) is although considered the gold standard for the diagnosis and is not preferred by the patients. Skin tests are not well tolerated, and in vitro tests, such as the basophil activation test and lymphocyte transformation, are of low sensitivity and specificity and their relevance is debatable. Based on current evidence, we propose a systematic clinical approach for timely differential diagnosis and management of rashes in children who present a cutaneous eruption while receiving a drug.
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Hipersensibilidade a Drogas , Infecções por Vírus Epstein-Barr , Exantema , Viroses , Criança , Hipersensibilidade a Drogas/diagnóstico , Exantema/diagnóstico , Herpesvirus Humano 4 , Humanos , Testes Cutâneos , Viroses/diagnósticoRESUMO
This review highlights the novelties in understanding the underlying immunologic mechanisms of drug hypersensitivity reactions (DHRs) with special reference to beta-lactams (BLs) in the pediatric population, as well as tiny changes in clinical classification and diagnosis of DHRs, in the last couple of years. BLs are still the most commonly prescribed and used antibiotics in children. Viral infections are very often in children, and they can provoke skin rashes which are difficult to differentiate from DHRs. The majority of children are incorrectly labeled as "allergic." Therefore, allergy to BLs in children is overdiagnosed. These children often receive suboptimal treatment with second-line broad-spectrum antibiotics, which are less effective, more costly, and associated with an increased risk of antibiotic-resistant infections. This prolongs hospitalization and thus more uses health care. The correct diagnosis of BL allergy in children is still an important and hot topic. This review has outlined the need for correct diagnosis of BL allergy in children and all the controversies encountered by pediatricians and pediatric allergists. It is also necessary to change the paradigm.
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Hipersensibilidade a Drogas , beta-Lactamas , Alergistas , Antibacterianos/efeitos adversos , Criança , Hipersensibilidade a Drogas/tratamento farmacológico , Hipersensibilidade a Drogas/terapia , Humanos , Testes Cutâneos , beta-Lactamas/efeitos adversosRESUMO
BACKGROUND: Antiepileptic drugs (AEDs) are widely used for the treatment of epilepsy, but they can be associated with the development of mainly delayed/non-immediate hypersensitivity reactions (HRs). Although these reactions are usually cutaneous, self-limited, and spontaneously resolve within days after drug discontinuation, sometime HR reactions to AEDs can be severe and life-threatening. AIM: This paper seeks to show examples on practical management of AED HRs in children starting from a review of what it is already known in literature. RESULTS: Risk factors include age, history of previous AEDs reactions, viral infections, concomitant medications, and genetic factors. The diagnostic workup consists of in vivo (intradermal testing and patch testing) and in vitro tests [serological investigation to exclude the role of viral infection, lymphocyte transformation test (LTT), cytokine detection in ELISpot assays, and granulysin (Grl) in flow cytometry. Treatment is based on a prompt drug discontinuation and mainly on the use of glucocorticoids. CONCLUSION: Dealing with AED HRs is challenging. The primary goal in the diagnosis and management of HRs to AEDs should be trying to accurately identify the causal trigger and simultaneously identify a safe and effective alternative anticonvulsant. There is therefore an ongoing need to improve our knowledge of HS reactions due to AED medications and in particular to improve our diagnostic capabilities.
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Hipersensibilidade a Drogas , Hipersensibilidade Tardia , Anticonvulsivantes/efeitos adversos , Criança , Hipersensibilidade a Drogas/tratamento farmacológico , Hipersensibilidade a Drogas/terapia , Humanos , Hipersensibilidade Tardia/diagnóstico , Hipersensibilidade Tardia/tratamento farmacológico , Testes Intradérmicos , Fatores de Risco , PeleRESUMO
The aim of this study was to identify short digestion-resistant peptides (SDRPs) released by pepsin digestion of the whole cow's milk and examine their IgE reactivity and allergenicity. Raw milk was subjected to simulated gastric digestion. SDRPs were fractionated from the digests and identified by MS. Milk SDRPs were evaluated for aggregability, propensity to compete for IgE binding with individual milk allergens, and ability to bind IgG4 from allergic and milk-tolerant individuals. The majority of milk SDRPs originated from caseins (97% of peptides) and overlapped with the known IgE epitopes of cow's milk allergens. SDRPs competed with milk proteins for binding to human IgE and readily formed aggregates. The average peptide length was 10.6 ± 3.5 amino acids. The ability to provoke allergenic in vivo responses was confirmed by skin-prick testing (SPT) in five milk-allergic subjects. This was attributed to the peptide ability to aggregate into non-covalent complexes. SDRPs are able to induce response in SPT, but only in 50% of the sera SDRPs were able to inhibit IgG4 binding to caseins. Hence, SDRPs corresponding to the mainly continuous epitopes of milk proteins induce allergenic in vivo responses in milk-allergic subjects due to aggregation.
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Coronavirus disease 2019 (COVID-19), a respiratory tract infection caused by a novel human coronavirus, the severe acute respiratory syndrome coronavirus 2, leads to a wide spectrum of clinical manifestations ranging from asymptomatic cases to patients with mild and severe symptoms, with or without pneumonia. Given the huge influence caused by the overwhelming COVID-19 pandemic affecting over three million people worldwide, a wide spectrum of drugs is considered for the treatment in the concept of repurposing and off-label use. There is no knowledge about the diagnosis and clinical management of the drug hypersensitivity reactions that can potentially occur during the disease. This review brings together all the published information about the diagnosis and management of drug hypersensitivity reactions due to current and candidate off-label drugs and highlights relevant recommendations. Furthermore, it gathers all the dermatologic manifestations reported during the disease for guiding the clinicians to establish a better differential diagnosis of drug hypersensitivity reactions in the course of the disease.
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COVID-19/complicações , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/tratamento farmacológico , Academias e Institutos , Hipersensibilidade a Drogas/complicações , Europa (Continente) , Humanos , PandemiasRESUMO
Drug hypersensitivity reactions (DHRs) are associated with high global morbidity and mortality. Cutaneous T cell-mediated reactions classically occur more than 6 hours after drug administration and include life-threatening conditions such as toxic epidermal necrolysis, Stevens-Johnson syndrome, and hypersensitivity syndrome. Over the last 20 years, significant advances have been made in our understanding of the pathogenesis of DHRs with the identification of human leukocyte antigens as predisposing factors. This has led to the development of pharmacogenetic screening tests, such as HLA-B*57:01 in abacavir therapy, which has successfully reduced the incidence of abacavir hypersensitivity reactions. We have completed a PRISMA-compliant systematic review to identify genetic associations that have been reported in DHRs. In total, 105 studies (5554 cases and 123 548 controls) have been included in the review reporting genetic associations with carbamazepine (n = 31), other aromatic antiepileptic drugs (n = 24), abacavir (n = 11), nevirapine (n = 14), trimethoprim-sulfamethoxazole (n = 11), dapsone (n = 4), allopurinol (n = 10), and other drugs (n = 5). The most commonly reported genetic variants associated with DHRs are located in human leukocyte antigen genes and genes involved in drug metabolism pathways. Increasing our understanding of genetic variants that contribute to DHRs will allow us to improve diagnosis, develop new treatments, and predict and prevent DHRs in the future.
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Síndrome de Hipersensibilidade a Medicamentos , Hipersensibilidade a Drogas , Preparações Farmacêuticas , Síndrome de Stevens-Johnson , Carbamazepina , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/epidemiologia , Hipersensibilidade a Drogas/genética , Síndrome de Hipersensibilidade a Medicamentos/diagnóstico , Síndrome de Hipersensibilidade a Medicamentos/epidemiologia , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Antígenos HLA-B/genética , Humanos , Linfócitos TRESUMO
BACKGROUND: Diagnosis of hypersensitivity (HS) reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) in children is complex. The real prevalence of NSAID HS remains unknown because a drug provocation test (DPT) is not always performed with the culprit NSAID. OBJECTIVE: To describe and compare the diagnostic workup among different European centers and to find out the real proportion of NSAID HS by performing a DPT with the culprit drug. METHODS: We retrospectively collected data from children (0-10 years) and adolescents (10-18 years) with a history of NSAID reactions and who underwent a complete allergy workup including DPTs with the culprit in 6 different pediatric centers: Belgrade, Florence, Geneva, Madrid, Porto, and Rome. RESULTS: A total of 693 children with a history of NSAID reactions were enrolled, and a total of 526 DPTs were performed with the culprit NSAID. The diagnosis of NSAID HS was confirmed in 19.6% (103 of 526) of children by performing a DPT with the culprit drug. The major differences in the allergy workup among the 6 centers concerned the duration of the DPT and the practical use of skin tests for diagnosing NSAID HS. In addition, the use of acetyl salicylic acid to differentiate single reactor or cross-intolerance patients is not common, except in Spain. CONCLUSION: The value of this study is that although different approaches are used around Europe to diagnose NSAID HS, we found that the percentage of confirmed NSAID HS is less than 20%. This highlights the importance of the DPT in confirming or excluding NSAID HS in the pediatric population.
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Hipersensibilidade a Drogas , Preparações Farmacêuticas , Adolescente , Anti-Inflamatórios não Esteroides/efeitos adversos , Criança , Pré-Escolar , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/epidemiologia , Europa (Continente) , Humanos , Estudos Retrospectivos , EspanhaRESUMO
Mobile health (mHealth) uses mobile communication devices such as smartphones and tablet computers to support and improve health-related services, data and information flow, patient self-management, surveillance, and disease management from the moment of first diagnosis to an optimized treatment. The European Academy of Allergy and Clinical Immunology created a task force to assess the state of the art and future potential of mHealth in allergology. The task force endorsed the "Be He@lthy, Be Mobile" WHO initiative and debated the quality, usability, efficiency, advantages, limitations, and risks of mobile solutions for allergic diseases. The results are summarized in this position paper, analyzing also the regulatory background with regard to the "General Data Protection Regulation" and Medical Directives of the European Community. The task force assessed the design, user engagement, content, potential of inducing behavioral change, credibility/accountability, and privacy policies of mHealth products. The perspectives of healthcare professionals and allergic patients are discussed, underlining the need of thorough investigation for an effective design of mHealth technologies as auxiliary tools to improve quality of care. Within the context of precision medicine, these could facilitate the change in perspective from clinician- to patient-centered care. The current and future potential of mHealth is then examined for specific areas of allergology, including allergic rhinitis, aerobiology, allergen immunotherapy, asthma, dermatological diseases, food allergies, anaphylaxis, insect venom, and drug allergy. The impact of mobile technologies and associated big data sets are outlined. Facts and recommendations for future mHealth initiatives within EAACI are listed.