Assuntos
Asma/imunologia , COVID-19/imunologia , Imunodeficiência de Variável Comum/imunologia , Deficiência de IgG/imunologia , Obesidade Mórbida/imunologia , Infecções Estafilocócicas/imunologia , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Adulto , Alanina/análogos & derivados , Alanina/uso terapêutico , Antivirais/uso terapêutico , Asma/patologia , Asma/terapia , Asma/virologia , COVID-19/patologia , COVID-19/terapia , COVID-19/virologia , Imunodeficiência de Variável Comum/patologia , Imunodeficiência de Variável Comum/terapia , Imunodeficiência de Variável Comum/virologia , Evolução Fatal , Humanos , Deficiência de IgG/patologia , Deficiência de IgG/terapia , Deficiência de IgG/virologia , Imunização Passiva , Imunoglobulina G/sangue , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Staphylococcus aureus Resistente à Meticilina , Obesidade Mórbida/patologia , Obesidade Mórbida/terapia , Obesidade Mórbida/virologia , SARS-CoV-2 , Infecções Estafilocócicas/patologia , Infecções Estafilocócicas/terapia , Infecções Estafilocócicas/virologia , Soroterapia para COVID-19RESUMO
These parameters were developed by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma & Immunology (AAAAI); the American College of Allergy, Asthma & Immunology (ACAAI); and the Joint Council of Allergy, Asthma and Immunology. The AAAAI and the ACAAI have jointly accepted responsibility for establishing "The Diagnosis and Management of Anaphylaxis Practice Parameter: 2010 Update." This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the Joint Task Force, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, or the Joint Council of Allergy, Asthma and Immunology. These parameters are not designed for use by pharmaceutical companies in drug promotion.
Assuntos
Anafilaxia , Alergia e Imunologia , Anafilaxia/diagnóstico , Anafilaxia/prevenção & controle , Anafilaxia/terapia , Gerenciamento Clínico , Humanos , Hipersensibilidade ao LátexRESUMO
gp49B1 is expressed on mast cells and inhibits immunoglobulin E-dependent activation and inflammation in vivo. We now show that gp49B1 is expressed on neutrophils and prevents neutrophil-dependent vascular injury in response to lipopolysaccharide (LPS). The intradermal (i.d.) injection of LPS into gp49B1-null (gp49B-/-) but not gp49B1-sufficient (gp49B+/+) mice elicited macroscopic hemorrhages by 24 h, which were preceded on microscopic analyses by significantly more intravascular thrombi (consisting of neutrophils, platelets, and fibrin) that occluded venules and by more tissue neutrophils than in gp49B+/+ mice. However, there were no differences in the number of intact (nondegranulating) mast cells or the tissue levels of mediators that promote neutrophil recruitment. Hemorrhage was prevented by depleting neutrophils, blocking beta2 integrin-intercellular adhesion molecule 1 interactions, or inhibiting coagulation. These characteristics indicate that gp49B-/- mice are exquisitely sensitive to a local Shwartzman reaction (LSR) after a single i.d. injection of LPS, whereas in the classic LSR, a second exposure is required for increased beta2 integrin function, intravascular neutrophil aggregation, formation of occlusive thrombi, and hemorrhage. Moreover, LPS increased gp49B1 expression on neutrophils in vivo. The results suggest that gp49B1 suppresses the LPS-induced increase in intravascular neutrophil adhesion, thereby providing critical innate protection against a pathologic response to a bacterial component.
Assuntos
Hemorragia/etiologia , Lipopolissacarídeos/farmacologia , Glicoproteínas de Membrana/metabolismo , Neutrófilos/metabolismo , Receptores Imunológicos/metabolismo , Trombose/etiologia , Animais , Adesão Celular , Masculino , Mastócitos/fisiologia , Glicoproteínas de Membrana/fisiologia , Camundongos , Camundongos Mutantes , Microcirculação , Receptores Imunológicos/fisiologia , VarfarinaRESUMO
Despite major progress in defining the genetic basis of Mendelian disorders, the molecular etiology of many cases remains unknown. Patients with these undiagnosed disorders often have complex presentations and require treatment by multiple health care specialists. Here, we describe an integrated clinical diagnostic and research program using whole-exome and whole-genome sequencing (WES/WGS) for Mendelian disease gene discovery. This program employs specific case ascertainment parameters, a WES/WGS computational analysis pipeline that is optimized for Mendelian disease gene discovery with variant callers tuned to specific inheritance modes, an interdisciplinary crowdsourcing strategy for genomic sequence analysis, matchmaking for additional cases, and integration of the findings regarding gene causality with the clinical management plan. The interdisciplinary gene discovery team includes clinical, computational, and experimental biomedical specialists who interact to identify the genetic etiology of the disease, and when so warranted, to devise improved or novel treatments for affected patients. This program effectively integrates the clinical and research missions of an academic medical center and affords both diagnostic and therapeutic options for patients suffering from genetic disease. It may therefore be germane to other academic medical institutions engaged in implementing genomic medicine programs.
RESUMO
Food-dependent, exercise-induced anaphylaxis is a disorder in which anaphylaxis develops most predictably during exercise, when exercise takes place within a few hours of ingesting a specific food. IgE to that food should be demonstrable. It is the combination of the food and exercise that precipitates attacks, whereas the food and exercise are each tolerated independently. Recently, it was demonstrated that exercise is not essential for the development of symptoms, and that if enough of the culprit food is ingested, often with additional augmentation factors, such as alcohol or acetylsalicylic acid, symptoms can be induced at rest in the challenge setting. Thus, food-dependent, exercise-induced anaphylaxis appears to be more correctly characterized as a food allergy syndrome in which symptoms develop only in the presence of various augmentation factors, with exercise being the primary one. However, additional factors are not usually present when the patient exercises normally, so ongoing investigation is needed into the physiologic and cellular changes that occur during exercise to facilitate food-induced anaphylaxis.
Assuntos
Anafilaxia/diagnóstico , Anafilaxia/terapia , Asma Induzida por Exercício/complicações , Hipersensibilidade Alimentar/complicações , Bebidas Alcoólicas/efeitos adversos , Assistência Ambulatorial , Anafilaxia/etiologia , Aspirina/imunologia , Gerenciamento Clínico , Feminino , Humanos , Imunoglobulina E/sangue , Pessoa de Meia-IdadeRESUMO
Exercise-induced anaphylaxis is an uncommon disorder in which anaphylaxis occurs in response to physical exertion. Food-dependent exercise-induced anaphylaxis is a disorder with similar symptoms, although symptoms develop only if exercise takes place within a few hours of eating and, in most cases, only if a specific food is eaten. Management includes education about safe conditions for exercise, the importance of ceasing exercise immediately if symptoms develop, appropriate use of epinephrine, and, for patients with food-dependent exercise-induced anaphylaxis, avoidance of the culprit food for at least 4 hours before exercise.
Assuntos
Anafilaxia/diagnóstico , Anafilaxia/etiologia , Exercício Físico , Anafilaxia/epidemiologia , Anafilaxia/mortalidade , Anafilaxia/prevenção & controle , Anafilaxia/terapia , Diagnóstico Diferencial , Gerenciamento Clínico , Alimentos/efeitos adversos , Humanos , Prognóstico , Fatores de RiscoRESUMO
BACKGROUND: A large percentage of patients with aspirin exacerbated respiratory disease (AERD) report the development of alcohol-induced respiratory reactions, but the true prevalence of respiratory reactions caused by alcoholic beverages in these patients was not known. OBJECTIVE: We sought to evaluate the incidence and characteristics of alcohol-induced respiratory reactions in patients with AERD. METHODS: A questionnaire designed to assess alcohol-induced respiratory symptoms was administered to patients at Brigham and Women's Hospital and Scripps Clinic. At least 50 patients were recruited into each of 4 clinical groups: (1) patients with aspirin challenge-confirmed AERD, (2) patients with aspirin-tolerant asthma (ATA), (3) patients with aspirin tolerance and with chronic rhinosinusitis, and (4) healthy controls. Two-tailed Fisher exact tests with Bonferroni corrections were used to compare the prevalence of respiratory symptoms among AERD and other groups, with P ≤ .017 considered significant. RESULTS: The prevalence of alcohol-induced upper (rhinorrhea and/or nasal congestion) respiratory reactions in patients with AERD was 75% compared with 33% with aspirin-tolerant asthma, 30% with chronic rhinosinusitis, and 14% with healthy controls (P < .001 for all comparisons). The prevalence of alcohol-induced lower (wheezing and/or dyspnea) respiratory reactions in AERD was 51% compared with 20% in aspirin-tolerant asthma and with 0% in both chronic rhinosinusitis and healthy controls (P < .001 for all comparisons). These reactions were generally not specific to one type of alcohol and often occurred after ingestion of only a few sips of alcohol. CONCLUSION: Alcohol ingestion causes respiratory reactions in the majority of patients with AERD, and clinicians should be aware that these alcohol-induced reactions are significantly more common in AERD than in controls who are aspirin tolerant.
Assuntos
Asma Induzida por Aspirina/complicações , Etanol/efeitos adversos , Transtornos Respiratórios/induzido quimicamente , Adulto , Idoso , Rinorreia de Líquido Cefalorraquidiano/induzido quimicamente , Dispneia/induzido quimicamente , Feminino , Humanos , Leucotrieno E4/urina , Masculino , Pessoa de Meia-Idade , Sons Respiratórios/efeitos dos fármacosRESUMO
OBJECTIVE: To report clinical cases of autoimmune progesterone (P) dermatitis, its relationship to IVF, and the potential for P desensitization to treat these cases to achieve viable pregnancies. DESIGN: Clinical description. SETTING: Institutional hospitalary practice. Allergy Division. PATIENT(S): Six patients from the Allergy Clinic consulting for cyclic rashes or anaphylaxis related to the luteal phase of the menstrual cycle. Three of the conditions were related to IVF. INTERVENTION(S): Skin tests were performed with P. For IVF, rapid 8- and 10-step P desensitization protocols were performed, with increasing doses administered every 20 minutes via intravaginal suppositories. A rapid oral desensitization protocol was performed in one patient who required an oral contraceptive for uterine bleeding. MAIN OUTCOME MEASURE(S): Progesterone skin test results. Tolerance to P desensitization. Achievement of viable pregnancies. RESULT(S): Skin tests were positive in all patients and negative in 10 controls. Desensitization was successful in four patients: three patients for IVF, resulting in viable pregnancies. Another patient achieved tolerance to oral contraceptives. CONCLUSION(S): Women with autoimmune P dermatitis can be desensitized successfully to P. We provide the first evidence of successful P desensitization in patients requiring IVF culminating in successful pregnancies.
Assuntos
Dessensibilização Imunológica/métodos , Toxidermias/imunologia , Fertilização in vitro , Infertilidade Feminina/tratamento farmacológico , Infertilidade Feminina/imunologia , Progesterona , Adulto , Doenças Autoimunes/imunologia , Feminino , Humanos , Gravidez , Resultado da Gravidez , Progesterona/administração & dosagem , Progesterona/efeitos adversos , Progesterona/imunologiaRESUMO
OBJECTIVE: Administration of paclitaxel is associated with hypersensitivity reactions (HSRs) in up to 9% of patients despite premedication. The purpose of this study was to evaluate the effectiveness of a standardized desensitization protocol in patients with HSRs to taxanes, based on our experience with carboplatin desensitization. METHODS: We analyzed seventeen consecutive patients with documented HSRs to taxanes who required continued treatment with a taxane agent. The patients were treated with either paclitaxel or docetaxel using the 6- to 7-h standard desensitization protocol. RESULTS: Seventeen patients who previously had severe taxane HSRs successfully completed 77 planned cycles of desensitization to paclitaxel or docetaxel, 72 of which were without reactions. Four patients developed HSRs during the desensitization protocol that were much less severe than their original HSRs and tolerated the re-administration of infusions without further reactions. Of these four patients, the first had palmar erythema 8 h after her 1st desensitization. The second patient had mild abdominal pain during her 1st cycle, and the third patient developed mild chest burning during her 2nd and 4th cycles. These three patients also completed subsequent desensitization cycles without reactions. The fourth patient developed a delayed urticaria reaction and gastrointestinal symptoms 6 h after completing her 1st desensitization. She elected to be treated with an alternative chemotherapy and did not receive additional courses of desensitization. CONCLUSION: The rapid standard desensitization protocol provides a safe and effective strategy for the re-administration of paclitaxel or docetaxel even after severe HSRs.
Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Dessensibilização Imunológica/métodos , Hipersensibilidade a Drogas/prevenção & controle , Neoplasias dos Genitais Femininos/tratamento farmacológico , Paclitaxel/administração & dosagem , Taxoides/administração & dosagem , Adulto , Idoso , Antineoplásicos Fitogênicos/efeitos adversos , Antineoplásicos Fitogênicos/imunologia , Neoplasias da Mama/imunologia , Docetaxel , Hipersensibilidade a Drogas/etiologia , Feminino , Neoplasias dos Genitais Femininos/imunologia , Humanos , Pessoa de Meia-Idade , Paclitaxel/efeitos adversos , Paclitaxel/imunologia , Taxoides/efeitos adversos , Taxoides/imunologiaRESUMO
We report that gp49B1, a mast cell membrane receptor with two immunoreceptor tyrosine-based inhibitory motifs (ITIM), constitutively inhibits mast cell activation-secretion induced by stem cell factor (SCF), a tissue-derived cytokine that also regulates mast cell development. The intradermal injection of SCF into the ears of gp49B1 null (gp49B(-/-)) mice elicited approximately 4- and 2.5-fold more degranulating mast cells and tissue swelling caused by edema, respectively, than in gp49B(+/+) mice. SCF did not induce tissue swelling in mast cell-deficient mice, and the responsiveness of gp49B(-/-) mice to mast cell-associated amine and lipid mediators was unaltered. When gp49B(+/+) and gp49B(-/-) mice were pretreated with antagonists of the amines, SCF-induced tissue swelling was reduced by >90% and 60%, respectively, and it was reduced by >90% in both genotypes when a cysteinyl leukotriene receptor antagonist was also provided. Hence, the dominant contribution of secretory granule amines to SCF-induced tissue swelling is the result of gp49B1-mediated inhibition of the production of cysteinyl leukotrienes by mast cells. Our findings also provide the first example of an ITIM-bearing receptor that constitutively suppresses inflammation generated in vivo independently of the adaptive immune response by a receptor that signals through intrinsic tyrosine kinase activity rather than immunoreceptor tyrosine-based activation motifs.