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BACKGROUND: Hypersensitivity reactions (HR) are common in mastocytosis. However, little is known about triggers and risk factors. The registry of the European Competence Network on Mastocytosis (ECNM) enables reliable studies in a larger cohort of mastocytosis patients. We assessed prevalence, triggers and risk factors of HR in adults with mastocytosis in the ECNM registry. METHODS: Data were collected in 27 ECNM centers. We analyzed potential triggers (Hymenoptera venoms, food, drug, inhalant and others) and risk factors at diagnosis and during follow-up. The study group consisted of 2485 adults with mastocytosis, 1379 women (55.5%) and 1106 men (44.5%). Median age was 48.2 years (range 18-91 years). RESULTS: Nine hundred and forty eight patients (38.1%) reported one or more HR`. Most common triggers were Hymenoptera venoms in cutaneous mastocytosis (CM) and indolent systemic mastocytosis (ISM), whereas in advanced SM (advSM), most common elicitors were drugs, including nonsteroidal anti-inflammatory agents and penicillin. In multivariate analyses, tryptase level < 90 ng/mL, <15% infiltration by mast cells in bone marrow biopsy-sections, and diagnosis of ISM were identified as independent risk factors for HR. For drug-induced HR, prominent risk factors were advSM and high tryptase levels. New reactions were observed in 4.8% of all patients during 4 years follow-up. CONCLUSIONS: HR are mainly triggered by Hymenoptera venoms in patients with CM and ISM and by drugs in patients with advSM. Tryptase levels <90 ng/mL, mast cell bone marrow infiltration <15%, and WHO category ISM are predictors of HR. New HR occur in 4.8% of all patients within 4 years.
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BACKGROUND: The diagnosis of allergic reactions to penicillins (AR-PEN) is very complex as there is a loss of sensitization over time, which leads to negative skin tests (STs) and specific IgE in serum, and even to tolerance to the drug involved. However, STs may become positive after subsequent exposure to the culprit drug (resensitization), with the risk of inducing potentially severe reactions. The exact rate of resensitization to penicillins is unknown, ranging from 0% to 27.9% in published studies. OBJECTIVES: To analyze the rate of resensitization in patients with suggestive AR-PEN by repeating STs (retest) after an initial evaluation (IE). MATERIAL AND METHODS: Patients with suspected AR-PEN were prospectively evaluated between 2017 and 2020. They underwent STs, and a randomized group also underwent a drug provocation test (DPT) with the culprit. Only patients with negative STs and/or DPT were included. All included cases were retested by STs at 2-8 weeks. RESULTS: A total of 545 patients were included: 296 reporting immediate reactions (IRs) and 249 non-immediate reactions (NIRs). Eighty (14.7%) cases had positive results in retest (RT+): 63 (21.3%) IRs and 17 (6.8%) NIRs (p < 0.0001). The rate of RT+ was higher in anaphylaxis compared with all other reactions (45.8% vs 9.1%, p < 0.0001). The risk of RT+ was higher from the fifth week after IE (OR: 4.64, CI: 2.1-11.6; p < 0.001) and increased with the patient's age (OR: 1.02; CI: 1.01-1.04; p = 0.009). CONCLUSIONS: Due to the high rate of resensitization, retest should be included in the diagnostic algorithm of IRs to penicillins after an initial negative study, especially in anaphylaxis, to avoid potentially severe reactions after subsequent prescriptions of these drugs.
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Anafilaxia , Hipersensibilidade a Drogas , Humanos , Anafilaxia/diagnóstico , Anafilaxia/induzido quimicamente , Testes Cutâneos/métodos , Imunoglobulina E , Penicilinas/efeitos adversos , Hipersensibilidade a Drogas/diagnóstico , Tetradecilsulfato de Sódio , Antibacterianos/efeitos adversosRESUMO
Conventional vaccines have been widely studied, along with their risk of causing allergic reactions. These generally consist of mild local reactions and only rarely severe anaphylaxis. Although all the current COVID-19 vaccines marketed in Europe have been shown to be safe overall in the general population, early post-marketing evidence has shown that mRNA-based vaccines using novel platforms (i.e., lipid nanoparticles) were associated with an increased risk of severe allergic reactions as compared to conventional vaccines. In this paper we performed an updated literature review on frequency, risk factors, and underlying mechanisms of COVID-19 vaccine-related allergies by searching MEDLINE and Google Scholar databases. We also conducted a qualitative search on VigiBase and EudraVigilance databases to identify reports of "Hypersensitivity" and "Anaphylactic reaction" potentially related to COVID-19 vaccines (Comirnaty, Spikevax, Vaxzevria and COVID-19 Janssen Vaccine), and in EudraVigilance to estimate the reporting rates of "Anaphylactic reaction" and "Anaphylactic shock" after COVID-19 vaccination in the European population. We also summarized the scientific societies' and regulatory agencies' recommendations for prevention and management of COVID-19 vaccine-related allergic reactions, especially in those with a history of allergy.
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Anafilaxia , Vacinas contra COVID-19 , Anafilaxia/epidemiologia , Anafilaxia/prevenção & controle , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Humanos , Lipossomos , Nanopartículas , Fatores de RiscoRESUMO
Systemic mastocytosis (SM) is a heterogeneous group of diseases that affect almost exclusively adults and are defined by the proliferation and accumulation of clonal mast cells (MC) in various tissues. Disease subtypes range from indolent to rare aggressive forms. Although SM is classified as a rare disease, it is believed to be likely underdiagnosed. Major signs and symptoms mainly depend on MC activation and less frequent organ infiltration, typical of more aggressive variants. Diagnosis may be challenging, and symptoms can be aspecific and involve several organs. Therefore, it is advisable to refer patients to specialized centers, having sufficient knowledge of the disease, sensitive diagnostic procedures, offering a personalized and multidisciplinary diagnostic approach, including at least hematological, allergological, dermatological, and rheumatological evaluations. A precise and timely diagnosis is required for: a) adequate counseling of patients and their physicians; b) beginning of symptomatic treatment (anti-mediator therapy); c) prevention of severe manifestations of the disease (i.e., recurrent anaphylaxis, osteoporosis, and bone fractures); d) cytoreductive treatment of advanced SM variants. This review summarizes the disease's main manifestations and describes the ideal diagnostic approach for adult patients with suspected SM, giving physicians the main notions for correct patient diagnosis and management. This review also highlights the importance of a multidisciplinary approach in this very complex disease.
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BACKGROUND: Up to 75% of patients with severe anaphylactic reactions after Hymenoptera sting are at risk of further severe reactions if re-stung. Venom immunotherapy (VIT) is highly effective in protecting individuals with ascertained Hymenoptera venom allergy (HVA) and previous severe reactions. After a 3- to 5-year VIT course, most patients remain protected after VIT discontinuation. Otherwise, a lifelong treatment should be considered in high-risk patients (eg, in mastocytosis). Several case reports evidenced that patients with mastocytosis and HVA, although protected during VIT, can re-experience severe and sometimes fatal reactions after VIT discontinuation. OBJECTIVE: To evaluate whether patients who lost protection after VIT discontinuation may suffer from clonal mast cell disorders. METHODS: The survey describes the characteristics of patients who received a full course of VIT for previous severe reactions and who experienced another severe reaction at re-sting after VIT discontinuation. Those with a Red Española de Mastocitosis score of 2 or more or a serum basal tryptase level of more than 25 ng/mL underwent a hematological workup (bone marrow biopsy, KIT mutation, expression of aberrant CD25) and/or skin biopsy. RESULTS: Nineteen patients (mean age, 56.3 years; 89.5% males) were evaluated. All of them had received at least 4 years of VIT and were protected. After VIT discontinuation they were re-stung and developed, in all but 1 case, severe anaphylactic reactions (12 with loss of consciousness, in the absence of urticaria/angioedema). Eighteen patients (94.7%) had a clonal mast cell disorder, 8 of them with normal tryptase. CONCLUSIONS: Looking at this selected population, we suggest that mastocytosis should be considered in patients developing severe reactions at re-sting after VIT discontinuation and, as a speculation, patients with mastocytosis and HVA should be VIT-treated lifelong.
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Anafilaxia/diagnóstico , Dessensibilização Imunológica/métodos , Hipersensibilidade/diagnóstico , Mordeduras e Picadas de Insetos/diagnóstico , Mastócitos/imunologia , Mastocitose/diagnóstico , Alérgenos/imunologia , Animais , Células Clonais , Feminino , Humanos , Himenópteros/imunologia , Masculino , Pessoa de Meia-Idade , Triptases/sangue , Inconsciência , Peçonhas/imunologia , Suspensão de TratamentoAssuntos
Angina Pectoris/imunologia , Hipersensibilidade/imunologia , Mordeduras e Picadas de Insetos/complicações , Vespas/imunologia , Angina Pectoris/diagnóstico , Angina Pectoris/terapia , Animais , Eletrocardiografia , Humanos , Hipersensibilidade/diagnóstico , Hipersensibilidade/terapia , Mordeduras e Picadas de Insetos/imunologia , Masculino , Pessoa de Meia-Idade , Síndrome , Venenos de Vespas/imunologiaAssuntos
Hipersensibilidade a Drogas , Hipersensibilidade , Mastocitose , Adulto , Anestesia Local , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/epidemiologia , Humanos , Mastócitos , Mastocitose/diagnóstico , Mastocitose/epidemiologia , Prevalência , Estudos RetrospectivosRESUMO
European Academy of Allergy and Clinical Immunology and World Allergy Organization. World Allergy and Asthma Congress. Milano, Italy, 22-26 June 2013 The European Academy of Allergy and Clinical Immunology and World Allergy Organization congress provided a meeting for researchers and clinicians interested in allergy and clinical immunology from all over the world and a unique opportunity to exchange experience with other professionals in this fields.
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Alergia e Imunologia , Dessensibilização Imunológica , Hipersensibilidade/imunologia , Hipersensibilidade/terapia , Alergia e Imunologia/educação , Alergia e Imunologia/tendências , Biomarcadores/metabolismo , Pesquisa Biomédica , Educação de Pós-Graduação em Medicina , Humanos , ItáliaRESUMO
Bronchodilators are central drugs in the management of patients with chronic obstructive pulmonary disease (COPD). Indacaterol was the first agent of the novel family of very long-acting ß2-agonists to be used as an inhaled bronchodilator for COPD and provides 24-hour therapeutic action, thus allowing once-daily administration. Data from clinical trials show that indacaterol has a bronchodilator effect similar to that of the anticholinergic tiotropium bromide and slightly higher efficacy compared with the long-acting ß2-agonists, salmeterol and formoterol. Moreover, the safety profile is excellent and comparable with that of placebo. Concerning adherence with drug treatment and real-life management in respect to long-acting ß2-agonists, once-daily dosing makes indacaterol more convenient for COPD patients and is likely to enhance patient adherence. Other very long-acting ß2-agonists currently in development include vilanterol, olodaterol, and carmoterol, and these have shown good characteristics for clinical use in the studies reported thus far.
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Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Broncodilatadores/uso terapêutico , Indanos/uso terapêutico , Pulmão/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Quinolonas/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Broncodilatadores/administração & dosagem , Broncodilatadores/efeitos adversos , Esquema de Medicação , Desenho de Fármacos , Humanos , Indanos/administração & dosagem , Indanos/efeitos adversos , Pulmão/fisiopatologia , Adesão à Medicação , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Quinolonas/administração & dosagem , Quinolonas/efeitos adversos , Fatores de Tempo , Resultado do TratamentoRESUMO
Mastocytosis is characterised by clonal proliferation of mast cells in the skin and in various internal organs, and by symptoms related to an acute release of mast cell-derived mediators. In 20-30 % of patients, mastocytosis occurs without the typical skin lesions of urticaria pigmentosa that are usually the first clinical sign of the disease. In these patients, anaphylaxis is often the presenting sign of the disease. We report three cases in which a cardiac emergency (cardiac arrest or ventricular fibrillation) was the first clinical manifestation of anaphylaxis associated with systemic mastocytosis. All patients were men, none of them had previous episodes of anaphylaxis or other mediator-related symptoms, and none had major pre-existing cardiovascular condition. An eliciting factor was identified in one case (a wasp sting), but one was found in the other two. Elevation of the serum tryptase suggested a mastocytosis, which was confirmed by bone marrow biopsy. This case series demonstrates that cardiovascular emergencies may be presenting signs of mastocytosis, and that elevation of serum tryptase after an acute cardiac event, if confirmed under basal conditions, may be useful for diagnosing this disease.
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Parada Cardíaca/etiologia , Mastocitose/complicações , Fibrilação Ventricular/etiologia , Idoso , Emergências , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Eosinophilic esophagitis is a chronic inflammatory disease of the esophagus, immune/antigens mediated, whose incidence is increasing both in adults and pediatric population. It is clinically characterised by symptoms related to esophageal dysfunction and associated with eosinophil-predominant esophageal inflammation. The role of atopy has been clearly demonstrated both in epidemiological and experimental studies and has important implications for diagnosis and therapy. In fact, many evidences show that food and inhalant allergens represent the most important factors involved in the progress of the disease. Several studies have reported that, in a range between 50 and 80%, patients with eosinophilic esophagitis have a prior history of atopy, and for them, the presence of allergic rhinitis, asthma or atopic dermatitis is frequent. Skin tests are able to identify in most patients the allergens involved, allowing a correct dietary approach in order to achieve the remission of symptoms and the biopsy normalization.