RESUMO
BACKGROUND: Hereditary angioedema with C1 inhibitor deficiency is characterized by recurrent, unpredictable swelling episodes caused by uncontrolled plasma kallikrein generation and excessive bradykinin release resulting from cleavage of high-molecular-weight kininogen. Lanadelumab (DX-2930) is a new kallikrein inhibitor with the potential for prophylactic treatment of hereditary angioedema with C1 inhibitor deficiency. METHODS: We conducted a phase 1b, multicenter, double-blind, placebo-controlled, multiple-ascending-dose trial. Patients with hereditary angioedema with C1 inhibitor deficiency were randomly assigned in a 2:1 ratio to receive either lanadelumab (24 patients) or placebo (13 patients), in two administrations 14 days apart. Patients assigned to lanadelumab were enrolled in sequential dose groups: total dose of 30 mg (4 patients), 100 mg (4 patients), 300 mg (5 patients), or 400 mg (11 patients). The pharmacodynamic profile of lanadelumab was assessed by measurement of plasma levels of cleaved high-molecular-weight kininogen, and efficacy was assessed by the rate of attacks of angioedema during a prespecified period (day 8 to day 50) in the 300-mg and 400-mg groups as compared with the placebo group. RESULTS: No discontinuations occurred because of adverse events, serious adverse events, or deaths in patients who received lanadelumab. The most common adverse events that emerged during treatment were attacks of angioedema, injection-site pain, and headache. Dose-proportional increases in serum concentrations of lanadelumab were observed; the mean elimination half-life was approximately 2 weeks. Lanadelumab at a dose of 300 mg or 400 mg reduced cleavage of high-molecular-weight kininogen in plasma from patients with hereditary angioedema with C1 inhibitor deficiency to levels approaching that from patients without the disorder. From day 8 to day 50, the 300-mg and 400-mg groups had 100% and 88% fewer attacks, respectively, than the placebo group. All patients in the 300-mg group and 82% (9 of 11) in the 400-mg group were attack-free, as compared with 27% (3 of 11) in the placebo group. CONCLUSIONS: In this small trial, administration of lanadelumab to patients with hereditary angioedema with C1 inhibitor deficiency reduced cleavage of high-molecular-weight kininogen and attacks of angioedema. (Funded by Dyax; ClinicalTrials.gov number, NCT02093923 .).
Assuntos
Angioedemas Hereditários/prevenção & controle , Anticorpos Monoclonais/administração & dosagem , Calicreína Plasmática/antagonistas & inibidores , Adulto , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/sangue , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais Humanizados , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: We conducted our first patient survey at the 2013 hereditary angioedema (HAE) patient summit and learned that, despite several novel therapies, the burden of disease was high. OBJECTIVE: To determine, from the patient's perspective, if any improvements in the current state of HAE care occurred over a two-year period between HAE patient summits. METHODS: A patient survey was conducted at the 2015 Hereditary Angioedema Association conference by using paper surveys that aimed at understanding the current state of HAE care. Questions included patient characteristics, burden of disease, and satisfaction with care and treatment options. Comparisons between patients with HAE with C1-inhibitor (HAE-C1INH) and patients with HAE with normal C1-inhibitor (HAE-nlC1INH), as well as between patients with HAE in 2013 and 2015, were performed by using χ2 tests. RESULTS: There were 232 surveys distributed, and 143 surveys were identified as complete for inclusion and analysis from patients with self-reported HAE. Most patients had type I or type II HAE (67.5% [n = 106]), with a smaller number of patients with HAE-nlC1INH (23.6% [n = 37]). In 2015, almost half of the patients with HAE-C1INH (47.1%) and 56.7% of the patients with HAE-nlC1INH experienced a delay of ≥10 years between initial symptoms and diagnosis. Among the patients with HAE-C1INH, 25% reported one or more attacks per week and another 48% reported experiencing one or more attacks per month (fewer than one attack per week). The patients with HAE-nlC1INH reported attacks more frequently than did the patients with HAE-C1INH (p = 0.002), with 59.5% who reported attacks at least once a week. Emergency care was reported one or more times per month in 5% of the patients with HAE-C1INH and in 24.3% of the patients with HAE-nlC1INH. CONCLUSION: Similar to 2013, although significant progress has been made, there is still a high burden of disease that faces patients with HAE.
Assuntos
Angioedemas Hereditários/epidemiologia , Efeitos Psicossociais da Doença , Pacientes , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Diagnóstico Tardio , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Qualidade da Assistência à Saúde , Inquéritos e Questionários , Estados Unidos/epidemiologia , Adulto JovemRESUMO
Importance: Current treatments for long-term prophylaxis in hereditary angioedema have limitations. Objective: To assess the efficacy of lanadelumab, a fully human monoclonal antibody that selectively inhibits active plasma kallikrein, in preventing hereditary angioedema attacks. Design, Setting, and Participants: Phase 3, randomized, double-blind, parallel-group, placebo-controlled trial conducted at 41 sites in Canada, Europe, Jordan, and the United States. Patients were randomized between March 3, 2016, and September 9, 2016; last day of follow-up was April 13, 2017. Randomization was 2:1 lanadelumab to placebo; patients assigned to lanadelumab were further randomized 1:1:1 to 1 of the 3 dose regimens. Patients 12 years or older with hereditary angioedema type I or II underwent a 4-week run-in period and those with 1 or more hereditary angioedema attacks during run-in were randomized. Interventions: Twenty-six-week treatment with subcutaneous lanadelumab 150 mg every 4 weeks (n = 28), 300 mg every 4 weeks (n = 29), 300 mg every 2 weeks (n = 27), or placebo (n = 41). All patients received injections every 2 weeks, with those in the every-4-week group receiving placebo in between active treatments. Main Outcome and Measures: Primary efficacy end point was the number of investigator-confirmed attacks of hereditary angioedema over the treatment period. Results: Among 125 patients randomized (mean age, 40.7 years [SD, 14.7 years]; 88 females [70.4%]; 113 white [90.4%]), 113 (90.4%) completed the study. During the run-in period, the mean number of hereditary angioedema attacks per month in the placebo group was 4.0; for the lanadelumab groups, 3.2 for the every-4-week 150-mg group; 3.7 for the every-4-week 300-mg group; and 3.5 for the every-2-week 300-mg group. During the treatment period, the mean number of attacks per month for the placebo group was 1.97; for the lanadelumab groups, 0.48 for the every-4-week 150-mg group; 0.53 for the every-4-week 300-mg group; and 0.26 for the every-2-week 300-mg group. Compared with placebo, the mean differences in the attack rate per month were -1.49 (95% CI, -1.90 to -1.08; P < .001); -1.44 (95% CI, -1.84 to -1.04; P < .001); and -1.71 (95% CI, -2.09 to -1.33; P < .001). The most commonly occurring adverse events with greater frequency in the lanadelumab treatment groups were injection site reactions (34.1% placebo, 52.4% lanadelumab) and dizziness (0% placebo, 6.0% lanadelumab). Conclusions and Relevance: Among patients with hereditary angioedema type I or II, treatment with subcutaneous lanadelumab for 26 weeks significantly reduced the attack rate compared with placebo. These findings support the use of lanadelumab as a prophylactic therapy for hereditary angioedema. Further research is needed to determine long-term safety and efficacy. Trial Registration: EudraCT Identifier: 2015-003943-20; ClinicalTrials.gov Identifier: NCT02586805.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Angioedema Hereditário Tipos I e II/prevenção & controle , Calicreína Plasmática/antagonistas & inibidores , Adolescente , Adulto , Idoso , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Criança , Método Duplo-Cego , Feminino , Angioedema Hereditário Tipos I e II/classificação , Humanos , Injeções Subcutâneas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Adulto JovemRESUMO
BACKGROUND: The evaluation of antibiotic immediate-type hypersensitivity is intricate because of nonstandardized skin testing and challenge method variability. OBJECTIVE: To determine the safety outcomes and risk factors for antibiotic challenge reactions in patients reporting a history of antibiotic immediate-type hypersensitivity. METHODS: A 5-year retrospective review of patients evaluated for immediate-type antibiotic allergy was conducted. Data analyzed included patient demographics, index reaction details, and outcomes of skin testing and challenges, classified as single-step or multistep. RESULTS: Antibiotic hypersensitivity history was identified in 211 patients: 78% to penicillins, 10% to fluoroquinolones, 7.6% to cephalosporins, and 3.8% to carbapenems. In total, 179 patients completed the challenges (median age 67 years, range 50-76 years, 56% women), and compared with nonchallenged patients, they reported nonanaphylactic (P < .001) and remote index (P = .003) reactions. Sixteen patients (8.9%) experienced challenge reactions (5 of 28 for single-step challenge, 11 of 151 for multistep challenge), and 11 of these patients had negative skin testing results before the challenge. Challenge-reactive patients were significantly younger (P = .007), more often women (P = .036), and had additional reported antibiotic allergies (P = .005). No correlation was detected between the reported index and observed challenge reaction severities (κ = -0.05, 95% confidence interval -0.34 to 0.24). Anaphylactic rates were similar during single-step and multistep challenges (3.6% vs 3.3%). CONCLUSION: In the present population, younger women with multiple reported antibiotic allergies were at greatest risk for challenge reactions. Negative skin testing results did not exclude reactions, and index severity was not predictive of challenge outcome. The multistep and full-dose methods demonstrated a comparable reaction risk for anaphylaxis.
Assuntos
Antibacterianos/efeitos adversos , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade Imediata/diagnóstico , Testes Cutâneos , Idoso , Antibacterianos/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados da Assistência ao Paciente , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Testes Cutâneos/efeitos adversos , Testes Cutâneos/métodosRESUMO
BACKGROUND: Hereditary angioedema (HAE) is a rare genetic disorder with substantial morbidity and mortality. Despite expanded choices for effective acute treatment, prophylactic options are more limited. Intravenous C1 esterase inhibitor (C1-INH[IV]) is licensed and used to prevent HAE symptoms. OBJECTIVE: To better understand patient experiences with using C1-INH(IV), including level of satisfaction and types and frequency of complications. METHODS: Fifty adult members (≥18 years of age) of the US HAE Association who had HAE type I or II completed a self-administered internet survey. Eligible participants were experiencing at least 1 HAE attack per month and must have been receiving treatment with C1-INH(IV) as prophylaxis or acute therapy. RESULTS: Almost all respondents (n = 47; 94%) were using C1-INH(IV) for HAE prophylaxis. Most patients reported administration of C1-INH(IV) through a peripheral vein (n = 34) and 19 were currently (n = 17) or previously (n = 2) using a central venous port. Most respondents (62%) who used a peripheral vein to administer treatment reported having difficulty finding a usable vein or getting the infusion to work properly at least some of the time. Issues accessing veins, exhausted veins, and frequency of attacks were the main reasons physicians recommended ports to respondents. Although ports allow easier administration of therapy, 47% of respondents with ports experienced problems such as occlusion, thrombosis, and infection. Respondents using C1-INH prophylaxis reported a mean of 2.3 attacks per month during the previous 6 months. CONCLUSION: The survey results identified clinical challenges with IV HAE medication use, including venous access issues and ongoing monthly attack occurrence despite prophylactic C1-INH(IV) administration.
Assuntos
Proteína Inibidora do Complemento C1/administração & dosagem , Angioedema Hereditário Tipos I e II/epidemiologia , Angioedema Hereditário Tipos I e II/terapia , Satisfação do Paciente , Administração Intravenosa , Adolescente , Adulto , Idoso , Proteína Inibidora do Complemento C1/efeitos adversos , Progressão da Doença , Feminino , Pesquisas sobre Atenção à Saúde , Angioedema Hereditário Tipos I e II/diagnóstico , Angioedema Hereditário Tipos I e II/prevenção & controle , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Fenótipo , Pré-Medicação , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto JovemRESUMO
Hereditary angioedema (HAE) is a rare genetic disease caused by a deficiency in functional C1-esterase inhibitor characterized by recurrent episodes of angioedema in the absence of associated urticaria. Subcutaneous swellings are experienced by virtually all patients with HAE, and dermatologists are likely to encounter this manifestation, requiring that they be knowledgeable about diagnosis and treatment options. Diagnosis of HAE is often delayed because several of the symptoms can mimic other disease states. Delays in diagnosis can lead to increased inappropriate treatment and decreased patient quality of life. Once a proper diagnosis is made, treatment needs to be targeted to the individual patient and includes on-demand therapy and an option for short- and long-term prophylaxis. On-demand therapy is required for all patients who are diagnosed with HAE and effective options include plasma-derived and recombinant C1 inhibitors, kallikrein inhibitors, and bradykinin B2-receptor antagonists. Options available for prophylaxis include plasma-derived C1 inhibitors, attenuated androgens, and antifibrinolytic agents, although the latter 2 options are associated with significant adverse events. This article reviews the diagnosis and options for effective management of patients with HAE.
Assuntos
Proteína Inibidora do Complemento C1/genética , Angioedema Hereditário Tipos I e II/tratamento farmacológico , Qualidade de Vida , Animais , Diagnóstico Tardio , Angioedema Hereditário Tipos I e II/diagnóstico , Angioedema Hereditário Tipos I e II/fisiopatologia , HumanosRESUMO
Availability of effective treatment for acute attacks is expected to transform the care of hereditary angioedema (HAE) patients. We felt that it would be of interest to test these assumptions by examining the perceptions of HAE patients regarding the impact that these therapies have had on their lives. Patients at a United States HAE Association summit meeting were asked to rate the burden of HAE currently and compare by recall with 2009 when these therapies were not available. Questions covered five domains: psychological/emotional status, ability to carry out daily activities, fear of suffocation, worry about their children inheriting HAE, and medication side effects. Data were analyzed using Wilcoxon signed-rank tests or analysis of variance. Responses were obtained from 134 self-identified HAE subjects: 85 type I, 21 type II, and 28 with normal C1 inhibitor (C1INH). Burden of disease showed significant improvement in all domains except worry about children inheriting HAE. With the introduction of newer therapies, subjects with the most severe burden of illness improved more than those with milder burdens. However, significant burden of illness remained. The availability of the current treatments has substantially improved the quality of life for HAE patients in the United States, similar to a survey of Danish HAE patients regarding the introduction of home treatment. Nevertheless, our study shows that a substantial burden of illness remains for HAE patients.
Assuntos
Angioedemas Hereditários/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Percepção , Atividades Cotidianas/psicologia , Angioedemas Hereditários/complicações , Angioedemas Hereditários/psicologia , Criança , Dinamarca , Progressão da Doença , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/psicologia , Medo/psicologia , Acessibilidade aos Serviços de Saúde , Humanos , Qualidade de Vida , Resultado do Tratamento , Estados UnidosRESUMO
Hereditary angioedema (HAE) is a chronic disease with a high burden of disease that is poorly understood and often misdiagnosed. Availability of treatments, including C1 esterase inhibitor (C1INH) replacement, ecallantide, and icatibant, marks a significant advance for HAE patients. We aimed to better understand the current state of HAE care, from a patient perspective, after the introduction of several novel therapies. One session of the United States Hereditary Angioedema Association 2013 patient summit was devoted to data collection for this study. Patients attending the summit were self-selected, and HAE diagnosis was self-reported. Survey questions assessed patient characteristics, burden of disease, and treatment. Participant responses were captured using an audience response system. We surveyed 149 (80%) type I and II HAE (HAE-C1INH) and 37 (20%) HAE with normal C1INH (HAE-nlC1INH) patients. HAE-C1INH (72%) and HAE-nlCINH patients (76%) equally reported that HAE had a significant impact on quality of life (QOL). A third of HAE-C1INH patients were diagnosed within one year of their first HAE attack, but another third reported a delay of more than 10 years. Most HAE-C1INH (88%) and HAE-nlC1INH (76%) patients had on-demand treatment available. HAE-C1INH patients frequently had an individual treatment plan (76%) compared with 50% of HAE-nlC1INH patients. Most HAE-C1INH patients went to the emergency department (ED) or were hospitalized less than once every six months (80%). Our findings show that HAE management is improving with good access to on-demand and prophylactic treatment options. However, HAE patients still have a significant burden of disease and continued research and educational efforts are needed.
Assuntos
Angioedemas Hereditários/diagnóstico , Angioedemas Hereditários/terapia , Adolescente , Adulto , Angioedemas Hereditários/epidemiologia , Angioedemas Hereditários/prevenção & controle , Criança , Pré-Escolar , Efeitos Psicossociais da Doença , Gerenciamento Clínico , Progressão da Doença , Humanos , Lactente , Pessoa de Meia-Idade , Recidiva , Inquéritos e Questionários , Adulto JovemRESUMO
OBJECTIVES: To evaluate the use of Cinryze (nanofiltered C1-esterase inhibitor [C1 INH-nf]) for the acute management and prevention of hereditary angioedema attacks in the subgroup of children and adolescents who participated in 2 placebo-controlled and 2 open-label extension studies. STUDY DESIGN: In the acute-attack treatment studies, the efficacy of 1000 U of C1 INH-nf (with an additional 1000 U given 1 hour later if needed) was assessed based on the time to the start of symptomatic relief and the proportion of patients experiencing relief within 4 hours of therapy. In the prophylaxis studies, C1 INH-nf 1000 U was given twice weekly, and efficacy was based on the frequency of attacks. RESULTS: Across 4 studies, 46 children received a total of 2237 C1 INH-nf infusions. The median time to the start of unequivocal relief in the acute-attack treatment study (n = 12) was 30 minutes with C1 INH-nf, compared with 2 hours for placebo. In the open-label extension (n = 22), clinical relief began within 4 hours of therapy in 89% of attacks. In the prophylaxis study (n = 4), the number of attacks was reduced by approximately 2-fold with C1 INH-nf compared with placebo. In the prophylaxis open-label extension (n = 23), the median monthly attack rate decreased from 3.0 before treatment to 0.39 with C1 INH-nf use. CONCLUSION: In children, C1 INH-nf was well tolerated, provided relief from symptoms of hereditary angioedema attacks, and reduced the rate of attacks.
Assuntos
Angioedemas Hereditários/tratamento farmacológico , Proteína Inibidora do Complemento C1/uso terapêutico , Angioedema Hereditário Tipos I e II/tratamento farmacológico , Adolescente , Angioedemas Hereditários/prevenção & controle , Criança , Pré-Escolar , Proteína Inibidora do Complemento C1/administração & dosagem , Proteína Inibidora do Complemento C1/efeitos adversos , Filtração , Angioedema Hereditário Tipos I e II/complicações , Humanos , Resultado do TratamentoAssuntos
Antineoplásicos/efeitos adversos , Carboplatina/efeitos adversos , Dessensibilização Imunológica , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/terapia , Oxaliplatina/efeitos adversos , Idoso , Dessensibilização Imunológica/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Testes CutâneosRESUMO
When faced with a patient with recurrent swelling, a thorough laboratory evaluation to determine the underlying etiology ensues. When the laboratory work-up is unrevealing, health care practitioners are frequently left in a quandary. This review will attempt to provide up-to-date information on how to approach the diagnosis and management of angioedema in a patient with normal laboratory values. The subtypes that will be reviewed in detail include: hereditary angioedema with normal C1 inhibitor (HAE with normal C1INH), drug-induced angioedema, and idiopathic angioedema. We present literature to aid the physician in the diagnosis and treatment of these disorders.
Assuntos
Angioedema/diagnóstico , Angioedema/metabolismo , Angioedema/fisiopatologia , Angioedema/terapia , Proteínas Inativadoras do Complemento 1/metabolismo , Proteína Inibidora do Complemento C1 , Diagnóstico Diferencial , HumanosRESUMO
BACKGROUND: Although the identification and management of anaphylaxis in an emergency department setting has been well studied, our understanding of the risk factors for admission in a community-based hospital is lacking. OBJECTIVE: To determine the demographics and the predictors of hospitalization, in patients presenting with anaphylaxis to a community-based emergency department (ED). METHODS: We performed a five-year retrospective chart review of all patients seen in the ED of Winthrop University Hospital, a community-based institution, with an International Classification of Diseases, 9(th)Edition code related to anaphylaxis. RESULTS: Fifty-eight visits met inclusion criteria, of which 34% resulted in hospital admission (95% CI: 22-48%). Univariate predictors for admission included (1) the involvement of 2, 3, and 4 organ systems (26%, 55%, and 75%, respectively; P < .02); (2) gastrointestinal symptoms vs no symptoms (59% vs 24%, P < .02); (3) non-sting (ingested and other allergens) vs insect sting allergen (50% vs 12.5%, P < .005); and (4) a history of an ED visit for anaphylaxis vs none (67% vs 30%, P < .05). Multivariate analysis (logistic regression) confirmed non-sting allergens (p < 0.02) and number of organ systems involved (P < .05) as independent predictors of hospitalization. CONCLUSION: In our study population, the involvement of multiple organ systems, particularly gastrointestinal involvement, a history of ED visits for anaphylaxis, and involvement of ingested or other allergens (non-sting) demonstrated higher admission rates.
Assuntos
Anafilaxia/diagnóstico , Anafilaxia/epidemiologia , Insuficiência de Múltiplos Órgãos/diagnóstico , Insuficiência de Múltiplos Órgãos/epidemiologia , Admissão do Paciente/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alérgenos/efeitos adversos , Alérgenos/imunologia , Anafilaxia/complicações , Criança , Pré-Escolar , Serviços Médicos de Emergência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/complicações , Prognóstico , Características de Residência , Estudos Retrospectivos , Fatores de Risco , Estados Unidos , Adulto JovemRESUMO
Hereditary angioedema (HAE) results from mutations in the C1-esterase inhibitor (C1 INH) gene that decrease production of C1 INH or render it dysfunctional. HAE is characterized by recurrent, unpredictable, bradykinin-mediated edema of the extremities, face, genitalia, trunk, gastrointestinal tract, or upper airway. Attacks causing laryngeal edema can be fatal. Patients with HAE need medications for acute attacks; some also require prophylaxis. Management requires consideration of the patient's disease burden and effect on the patient's quality of life. This review examines an individualized approach to identifying HAE patients who may benefit from prophylaxis. A literature search was performed for HAE and prophylaxis. HAE guidelines, case reports, safety studies, and randomized, controlled clinical prophylaxis trials were selected. Authors provided cases demonstrating individualized prophylaxis. U.S. Food and Drug Administration-approved options for prophylaxis of HAE include attenuated androgens and nanofiltered C1 INH (C1 INH-nf). In other countries, pasteurized C1 INH and purified C1 INH are also available. Alternative therapies include fresh frozen plasma for preprocedural prophylaxis and antifibrinolytics for long-term prophylaxis. Attenuated androgens reduce attack frequency in many patients. Adverse effects include weight gain, virilization, increased hair growth, hypercholesterolemia, depression, and liver adenomas. C1 INH-nf reduces frequency of attacks and is well tolerated. Each patient with HAE has unique needs, based on the nature and frequency of past attacks, proximity to a medical center, occupation, and the patient's wishes. These factors should be used to create a patient-centered approach to management of HAE.
Assuntos
Angioedemas Hereditários/tratamento farmacológico , Proteína Inibidora do Complemento C1/uso terapêutico , Adulto , Angioedemas Hereditários/diagnóstico , Feminino , Humanos , Pré-Medicação , Estados UnidosRESUMO
Induction of tolerance protocols have been applied successfully to manage allergic reactions to many medications. Hypersensitivity reactions to natalizumab (TYSABRI®) have been recognized as a growing problem. In circumstances where a hypersensitivity reaction to a medication has occurred, but no suitable alternative exists, drug induction of tolerance protocols may be considered. Drug induction of tolerance protocols were performed in three patients with prior hypersensitivity reactions to natalizumab. All three patients tolerated the protocol without adverse reactions, allowing for the safe reintroduction of natalizumab. To conclude, this case series demonstrates success with an induction of tolerance procedure to a highly effective biological agent for multiple sclerosis, in patients with allergic reactions to natalizumab.
Assuntos
Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Dessensibilização Imunológica/métodos , Hipersensibilidade a Drogas/tratamento farmacológico , Tolerância Imunológica , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/efeitos adversos , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados , Hipersensibilidade a Drogas/etiologia , Hipersensibilidade a Drogas/imunologia , Feminino , Humanos , Infusões Parenterais , Pessoa de Meia-Idade , Natalizumab , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Studies assessing patch testing (PT) in allergy practices are limited. OBJECTIVES: To determine whether PT results using a limited panel of allergens such as in the Thin-Layer Rapid-Use Epicutaneous Test (TT) as compared with an expanded panel, such as the addition of supplemental allergens (North American Contact Dermatitis [NACD] Panel, Dormer Cosmetics, hairdressing series, corticosteroid series, and personal products) will miss a significant number of positive PTs. To compare our PT results with published data from dermatology practices. METHODS: This is a 5-year multicenter retrospective chart review of PT at 3 separate allergy practices. RESULTS: Four hundred twenty-seven patients (mean age, 49.8 years) were patch tested. Eighty-two percent were female; 54% reported an atopic history. Of the standardized allergens, the 5 most common positives were nickel sulfate, fragrance mix I, p-phenylenediamine (PPD), thimerosal, and cobalt chloride. Two hundred eighteen (56.9%; 95% CI = 51.9-61.8%) patients were positive to at least 1 TT allergen. Ninety-eight (25.6%; 95% CI = 21.5-30.2%) patients were positive to both a TT and a supplemental allergen. Forty-eight (12.5%; 95% CI = 9.6-16.2%) patients were negative to a TT allergen but positive to a supplemental allergen. CONCLUSION: Positive allergens would have been missed in 12.5% of patients when evaluating with TT allergens alone, whereas 25.6% would be partially evaluated. Patch test performance characteristics for these allergy practices appear to parallel that seen for dermatology. The TT remains an adequate screening tool in an allergy practice, but a more comprehensive panel may be needed to fully evaluate contact dermatitis.
Assuntos
Alérgenos/análise , Dermatite Alérgica de Contato/diagnóstico , Testes do Emplastro/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alérgenos/imunologia , Criança , Pré-Escolar , Dermatite Alérgica de Contato/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes do Emplastro/normas , Estudos Retrospectivos , Adulto JovemRESUMO
Scientific and clinical progress together with the development of effective novel therapeutic options has engendered multiple important changes in the diagnosis and management of hereditary angioedema (HAE). We now update and extend the 2013 United States Hereditary Angioedema Association Medical Advisory Board guidelines for the treatment and management of HAE. The guidelines are based on a comprehensive literature review with recommendations indicating both the strength of our recommendation and the quality of the underlying evidence. Guidelines are provided regarding the classification, diagnosis, on-demand treatment, prophylactic treatment, special considerations for women and children, development of a comprehensive management and monitoring plan, and assessment of burden of illness for both HAE due to C1 inhibitor deficiency and HAE with normal C1 inhibitor. Advances in HAE treatment now allow the development of management plans that can help many patients with HAE lead a normal life. Achieving this goal requires that physicians be familiar with the diagnostic and therapeutic transformations that have occurred in recent years.
Assuntos
Angioedemas Hereditários , Médicos , Comitês Consultivos , Angioedemas Hereditários/diagnóstico , Angioedemas Hereditários/tratamento farmacológico , Criança , Proteína Inibidora do Complemento C1 , Feminino , Humanos , Estados UnidosRESUMO
BACKGROUND: Hereditary angioedema (HAE) symptoms may be triggered by dental procedures, thereby complicating dental care in individuals affected by the condition. OBJECTIVE: This study investigated the self-perceived dental care needs, perceived susceptibility to acute angioedema (AE) attacks after dental procedures, and dental care behavior of patients with HAE. METHODS: A self-administered semistructured web-based questionnaire was distributed to 250 adult patients with HAE (type 1 or 2; 88% type 1) and 256 matched non-HAE controls. Data were analyzed using stratified χ2 tests, logistic regression, and classification trees. RESULTS: A total of 46.4% of HAE versus 55.5% of control patients had dental visits within 6 months (P = .04). Dental insurance was a barrier to seeking routine dental visits among both groups. However, significantly fewer patients with HAE had routine dental visits within 6 months despite having dental insurance compared with control patients (48% vs 60%, P = .01). Within the HAE group, a significantly greater number of patients with dental visits at intervals greater than 6 months had a history of recurrent postprocedural AE attacks (odds ratio [OR]: 3.9 [1.7, 8.8], P = .0005) and used antibacterial toothpaste more frequently than those without recurrent AE attacks (OR: 4.7 [1.5, 15.4], P = .005). CONCLUSIONS: These data support the hypothesis that patients with HAE who are predisposed to having AE episodes in response to medical or physical trauma visit the dentist less and engage in specific oral hygiene practices more frequently than matched control patients and patients with HAE who reported that they were less likely to swell after a dental procedure.
Assuntos
Angioedema , Angioedemas Hereditários , Adulto , Angioedemas Hereditários/epidemiologia , Proteína Inibidora do Complemento C1 , Humanos , Higiene Bucal , Autorrelato , Inquéritos e QuestionáriosRESUMO
Hereditary angioedema (HAE) is a rare genetic disease resulting in unpredictable and potentially life-threatening subcutaneous and submucosal attacks mediated by the vasoactive peptide, bradykinin. HAE often presents within the first or second decade of life, with attacks increasing in both frequency and severity over time. First-line therapies exert their action by replacing C1 inhibitor (C1-INH) or via blocking the production or function of bradykinin. Cinryze® is a nanofiltered C1-INH, approved in Europe for the acute treatment, preprocedure prevention and routine prophylaxis of HAE attacks, and for routine prophylaxis of attacks in the USA. Of the current C1-INH preparations available, Cinryze shows particular promise in the safe and effective treatment and prophylaxis of HAE attacks in pediatric age patients.