RESUMO
BACKGROUND: Although immune checkpoint blockade (ICB) therapy has proven to be extremely effective at managing certain cancers, its efficacy in treating pancreatic ductal adenocarcinoma (PDAC) has been limited. Therefore, enhancing the effect of ICB could improve the prognosis of PDAC. In this study, we focused on the histamine receptor H1 (HRH1) and investigated its impact on ICB therapy for PDAC. METHODS: We assessed HRH1 expression in pancreatic cancer cell (PCC) specimens from PDAC patients through public data analysis and immunohistochemical (IHC) staining. The impact of HRH1 in PCCs was evaluated using HRH1 antagonists and small hairpin RNA (shRNA). Techniques including Western blot, flow cytometry, quantitative reverse transcription polymerase chain reaction (RT-PCR), and microarray analyses were performed to identify the relationships between HRH1 and major histocompatibility complex class I (MHC-I) expression in cancer cells. We combined HRH1 antagonism or knockdown with anti-programmed death receptor 1 (αPD-1) therapy in orthotopic models, employing IHC, immunofluorescence, and hematoxylin and eosin staining for assessment. RESULTS: HRH1 expression in cancer cells was negatively correlated with HLA-ABC expression, CD8+ T cells, and cytotoxic CD8+ T cells. Our findings indicate that HRH1 blockade upregulates MHC-I expression in PCCs via cholesterol biosynthesis signaling. In the orthotopic model, the combined inhibition of HRH1 and αPD-1 blockade enhanced cytotoxic CD8+ T cell penetration and efficacy, overcoming resistance to ICB therapy. CONCLUSIONS: HRH1 plays an immunosuppressive role in cancer cells. Consequently, HRH1 intervention may be a promising method to amplify the responsiveness of PDAC to immunotherapy.
Assuntos
Inibidores de Checkpoint Imunológico , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/genética , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Camundongos , Animais , Receptores Histamínicos H1/metabolismo , Receptores Histamínicos H1/genética , Antígenos de Histocompatibilidade Classe I/metabolismo , Antígenos de Histocompatibilidade Classe I/genética , Linhagem Celular Tumoral , Feminino , Antagonistas dos Receptores Histamínicos H1/farmacologia , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , MasculinoRESUMO
BACKGROUND: There is a lack of real-life safety data on treatment options for chronic urticaria in the presence of comedication and comorbidities. METHODS: We present a single-center UCARE pilot study of 212 outpatients with chronic urticaria. Patients were divided into three groups according to different CU therapies according to international guidelines. RESULTS: Of 212 patients, 108 (mean age 48.9 years, 71.3% female) had 59 comorbidities, including cardiovascular, autoimmune and malignant diseases. Patients were followed for a mean of 24.6 months (SD ± 21.3). Urticaria therapies were divided into three groups: A: 105 (97.2%) with omalizumab and 2nd generation antihistamines), B: 16 patients (14.8%): dual therapy with antihistamines and cyclosporine in 10 (9.3%), montelukast in five (4. 6%), dapsone in four (3.7%), hydroxychloroquine in one patient (0.9%), C: 12 (11.1%) patients received a third drug for 4.9 months (SD ± 3.2) and one quadruple therapy (2.1 months). 10 out of 12 (83.3%) patients received montelukast, two (16.7%) cyclosporine, two (16.7%) dapsone and one (8.3%) hydroxychloroquine as a third drug for chronic urticaria. CONCLUSIONS: Combining treatment modalities for chronic urticaria and comorbidities are available and feasible with a good safety profile.
Assuntos
Acetatos , Antialérgicos , Urticária Crônica , Ciclopropanos , Quinolinas , Sulfetos , Urticária , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Hidroxicloroquina/uso terapêutico , Projetos Piloto , Doença Crônica , Urticária Crônica/tratamento farmacológico , Urticária/tratamento farmacológico , Omalizumab/uso terapêutico , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Ciclosporina/uso terapêutico , Dapsona/uso terapêutico , Antialérgicos/uso terapêuticoRESUMO
INTRODUCTION: Anxiety and nosocomial infection are the most common reported problems in children undergoing cleft surgeries. Research shows that there is an enigma in the use of antihistamine therapy in children for the management of upper respiratory tract infection. 'Promethazine' is a first-generation H1 receptor antagonist, and antihistamine also has strong sedative effects. Our study aims at evaluating the Effectiveness of Promethazine (Phenergan) in preoperative and intra operative sequelae in cleft surgeries. MATERIALS AND METHODS: This is a single-centre, parallel, randomized, double-blinded randomized control clinical trial, which was conducted among 128 children between 2 and 4 years of age undergoing cleft palate surgery under general anaesthesia. After randomization, the case group was subjected to promethazine syrup 1 mg/kg body weight twice a day, orally for 3 days. The primary outcomes were preoperative anxiety levels which were recorded by children fear scale. The secondary outcomes include preoperative sleep quality and cough rate of children which are recorded by using sleep and cough objective scale respectively. The intraoperative heart rate is monitored with an ECG connected to a monitor. RESULTS: Promethazine causes a reduction in the anxiety level by 70%, 64% reduction in cold and cough, improvement in sleep score by 70% and the heart rate was found to be stable throughout the surgery when compared to the control group. CONCLUSION: As the benefits of promethazine in cleft palate surgery rule over its adverse effects, promethazine is considered safe to be used as premedication for children undergoing cleft palate surgeries.
Assuntos
Fissura Palatina , Prometazina , Humanos , Prometazina/uso terapêutico , Fissura Palatina/cirurgia , Pré-Escolar , Masculino , Feminino , Método Duplo-Cego , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Ansiedade , Cuidados Pré-Operatórios , Resultado do Tratamento , Frequência Cardíaca/efeitos dos fármacos , Período Pré-OperatórioRESUMO
PURPOSE: Paclitaxel is associated with hypersensitivity reactions (HSRs). Intravenous premedication regimens have been devised to decrease the incidence and severity of HSRs. At our institution oral histamine 1 receptor antagonists (H1RA) and histamine 2 receptor antagonists (H2RA) were adopted as standard. Standardizations were implemented for consistent premedication use in all disease states. The purpose of this retrospective study was to compare the incidence and severity of HSRs before and after standardization. METHODS: Patients who received paclitaxel from 20 April 2018 to 8 December 2020 having an HSR were included in analysis. An infusion was flagged for review if a rescue medication was administered after the start of the paclitaxel infusion. The incidences of all HSR prior to and post-standardization were compared. A subgroup analysis of patients receiving paclitaxel for the first and second time was performed. RESULTS: There were 3499infusions in the pre-standardization group and 1159infusions in the post-standardization group. After review, 100 HSRs pre-standardization and 38 HSRs post-standardization were confirmed reactions. The rate of overall HSRs was 2.9% in the pre-standardization group and 3.3% in the post-standardization group (p = 0.48). HSRs, during the first and second doses of paclitaxel, occurred in 10.2% of the pre-standardization and 8.5% of the post-standardization group (p = 0.55). CONCLUSIONS: This retrospective interventional study demonstrated that same-day intravenous dexamethasone, oral H1RA, and oral H2RA are safe premedication regimens for paclitaxel. No change in the severity of reactions was seen. Overall, better adherence to premedication administration was seen post-standardization.
Assuntos
Antineoplásicos Fitogênicos , Hipersensibilidade a Drogas , Antagonistas dos Receptores Histamínicos H1 , Antagonistas dos Receptores H2 da Histamina , Paclitaxel , Humanos , Dexametasona/uso terapêutico , Hipersensibilidade a Drogas/epidemiologia , Hipersensibilidade a Drogas/prevenção & controle , Hipersensibilidade a Drogas/tratamento farmacológico , Histamina , Antagonistas dos Receptores Histamínicos H1/administração & dosagem , Paclitaxel/uso terapêutico , Pré-Medicação/efeitos adversos , Estudos Retrospectivos , Antagonistas dos Receptores H2 da Histamina/administração & dosagemRESUMO
Recently, a cellular mini-immune system comprising infinitely expandable dendritic cells and T cells led to the discovery that histamine receptor H1 antagonists act on T cells to stimulate their proliferation and polarization toward a Th1/Tc1 phenotype and to increase their anticancer activity in the context of immunochemotherapy.
Assuntos
Antagonistas dos Receptores Histamínicos , Neoplasias , Humanos , Monitorização Imunológica , Antagonistas dos Receptores Histamínicos H1 , Neoplasias/tratamento farmacológico , Linfócitos TRESUMO
BACKGROUND: Panic disorder and panic attacks are two of the most common problems in psychiatry. A psychoimmunological correlation between allergic diseases and panic disorder has been strongly suggested. Histamine H1 receptor antagonists have been suggested as alternative drugs for the treatment of panic disorder. Chronic spontaneous urticaria (CSU) and panic disorder improved simultaneously with selective serotonin reuptake inhibitor antidepressants. Panic disorder has also been treated with the antihistamine chlorpheniramine. The immunoglobulin/histamine complex is a histamine-fixed immunoglobulin preparation that was reported to be effective in treating CSU. This case report describes the successful treatment of a patient with concomitant panic disorder and CSU for 23 years using immunoglobulin/histamine complex therapy. CASE PRESENTATION: This report describes a 52-year-old female Korean patient who suffered from CSU with panic disorder for 23 years. Basic allergy tests (blood tests and skin prick tests) were conducted before and after treatment for the evaluation of allergic conditions. A multiple allergosorbent test (MAST) for the detection of allergen-specific IgE levels was also performed. The clinical severity of CSU was evaluated using the urticaria severity score system. Diagnostic interviews systematically assessed the diagnostic criteria outlined by the DSM-V, and the patient was evaluated before, during and after treatment using the Beck Depression Inventory (BDI-2) for depression, the State-Trait Anxiety Inventory (STAI) for anxiety and the Beck Hopelessness Score (BHS) for hopelessness. The patient received 2 ml of Histobulin™ (12 mg human immunoglobulin/0.15 µg histamine complex) once a week by subcutaneous injection for the treatment of CSU. Initial improvement of CSU was achieved after the third injection. After the twenty-seventh injection of Histobulin™, she showed no symptoms or signs and ceased allergic medication use. With the remission of CSU, allergic rhinitis was also completely resolved. The frequency of the common cold was significantly decreased during and after treatment. The medication frequency and development of clinical manifestations of panic disorder changed in parallel with the clinical severity of CSU. Moreover, the patient exhibited no clinical manifestations and ceased medication for panic disorder and sleeping pills for insomnia simultaneously with the remission of CSU. In the psychological evaluation, the BDI, STAI and BHS scores improved accordingly. CONCLUSIONS: The immunoglobulin/histamine complex was effective in treating CSU and concomitant panic disorder in this patient and could be effective in treating some types of panic disorder. Considering the mechanisms of action of histamine and the immunoglobulin/histamine complex together with the patient's clinical progress, histamine seemed to be related to panic disorder in this case. The concept of histamine-mediated syndromes, including allergies and psychiatric disorders, shows that a wider disease identity may be needed. Further studies on the immunopathogenesis of panic disorder and the mechanisms of action of the immunoglobulin/histamine complex are necessary.
Assuntos
Urticária Crônica , Transtorno de Pânico , Urticária , Feminino , Humanos , Pessoa de Meia-Idade , Histamina/uso terapêutico , Transtorno de Pânico/complicações , Transtorno de Pânico/tratamento farmacológico , Doença Crônica , Urticária Crônica/complicações , Urticária Crônica/tratamento farmacológico , Urticária/complicações , Urticária/tratamento farmacológico , Urticária/diagnóstico , Antagonistas dos Receptores Histamínicos H1/uso terapêuticoRESUMO
Kaposi sarcoma (KS) is one of the most common AIDS-related malignant neoplasms, which can leave lesions on the skin among HIV patients. These lesions can be treated with 9-cis-retinoic acid (9-cis-RA), an endogenous ligand of retinoic acid receptors that has been FDA-approved for treatment of KS. However, topical application of 9-cis-RA can induce several unpleasant side effects, like headache, hyperlipidemia, and nausea. Hence, alternative therapeutics with less side effects are desirable. There are case reports associating over-the-counter antihistamine usage with regression of KS. Antihistamines competitively bind to H1 receptor and block the action of histamine, best known for being released in response to allergens. Furthermore, there are already dozens of antihistamines that are FDA-approved with less side effects than 9-cis-RA. This led our team to conduct a series of in-silico assays to determine whether antihistamines can activate retinoic acid receptors. First, we utilized high-throughput virtual screening and molecular dynamics simulations to model high-affinity interactions between antihistamines and retinoic acid receptor beta (RARß). We then performed systems genetics analysis to identify a genetic association between H1 receptor itself and molecular pathways involved in KS. Together, these findings advocate for exploration of antihistamines against KS, starting with our two promising hit compounds, bepotastine and hydroxyzine, for experimental validation study in the future.
Assuntos
Infecções por HIV , Simulação de Dinâmica Molecular , Humanos , Receptores Histamínicos H1/genética , Receptores do Ácido Retinoico/genética , Receptores do Ácido Retinoico/metabolismo , Antagonistas dos Receptores Histamínicos/farmacologia , Antagonistas dos Receptores Histamínicos/uso terapêutico , Antagonistas dos Receptores Histamínicos H1/farmacologia , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Alitretinoína , Tretinoína/metabolismo , Tretinoína/farmacologiaRESUMO
Histamine is a biogenic amine implicated in various biological and pathological processes. Convenient cellular models are needed to screen and develop new antihistamine agents. This report aimed to characterize the response of neurons differentiated from mouse P19 embryonal carcinoma cells to histamine treatment, and to investigate the modulation of this response by antihistamine drugs, vegetal diamine oxidase, and catalase. The exposure of P19 neurons to histamine reduced cell viability to 65% maximally. This effect involves specific histamine receptors, since it was prevented by treatment with desloratadine and cimetidine, respectively, H1 and H2 antagonists, but not by the H3 antagonist ciproxifan. RT-PCR analysis showed that P19 neurons express H1 and H2 receptors, and the H3 receptor, although it seemed not involved in the histamine effect on these cells. The H4 receptor was not expressed. H1 and H2 antagonists as well as vegetal diamine oxidase diminished the intracellular Ca2+ mobilization triggered by histamine. The treatment with vegetal diamine oxidase or catalase protected against mortality and a significant reduction of H2O2 level, generated from the cells under the histamine action, was found upon treatments with desloratadine, cimetidine, vegetal diamine oxidase, or catalase. Overall, the results indicate the expression of functional histamine receptors and open the possibility of using P19 neurons as model system to study the roles of histamine and related drugs in neuronal pathogenesis. This model is less expensive to operate and can be easily implemented by current laboratories of analysis and by Contract Research Organizations.
Assuntos
Amina Oxidase (contendo Cobre) , Produtos Biológicos , Animais , Camundongos , Histamina/farmacologia , Histamina/metabolismo , Cimetidina/farmacologia , Catalase , Peróxido de Hidrogênio/farmacologia , Antagonistas dos Receptores Histamínicos/farmacologia , Receptores Histamínicos/genética , Antagonistas dos Receptores Histamínicos H1/farmacologia , Neurônios/metabolismo , Produtos Biológicos/farmacologiaRESUMO
Numerous studies have confirmed that in addition to interfering with the tumor inflammatory environment, anti-inflammatory agents can directly increase apoptosis and sensitivity to conventional therapies and decrease invasion and metastasis, making them useful candidates for cancer therapy. Here, we first used high-throughput screening and had screened one compound candidate, ebastine (a H1-histamine receptor antagonist), for osteosarcoma therapy. Cell viability assays, colony formation assays, wound healing assays, and Transwell assays demonstrated that ebastine elicited antitumor effects in osteosarcoma cells. In addition, ebastine treatment exerted obvious effects on cell cycle arrest, metastasis inhibition, apoptosis and autophagy induction both in vitro and in vivo. Mechanistically, we observed that ebastine treatment triggered proapoptotic autophagy by activating AMPK/ULK1 signaling in osteosarcoma cells. Treatment with the AMPK inhibitor dorsomorphin reversed ebastine-induced apoptosis and autophagy. More importantly, we found that IPMK interacted with AMPK and functioned as a positive regulator of AMPK protein in osteosarcoma cells. A rescue study showed that the induction of autophagy and activation of the AMPK/ULK1 signaling pathway by ebastine treatment were reversed by IPMK knockdown, indicating that the activity of ebastine was IPMK dependent. We provide experimental evidence demonstrating that ebastine has antitumor activity in osteosarcoma and promotes autophagy by activating the AMPK/ULK1 signaling pathway, which is IPMK dependent. Our results provide insight into the clinical application potential of ebastine, which may represent a new potential therapeutic candidate for the treatment of osteosarcoma.
Assuntos
Autofagia , Neoplasias Ósseas , Antagonistas dos Receptores Histamínicos H1 , Osteossarcoma , Humanos , Proteínas Quinases Ativadas por AMP/metabolismo , Autofagia/efeitos dos fármacos , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/genética , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Neoplasias Ósseas/tratamento farmacológico , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Osteossarcoma/tratamento farmacológico , Transdução de Sinais , Antagonistas dos Receptores Histamínicos H1/farmacologia , Antagonistas dos Receptores Histamínicos H1/uso terapêuticoRESUMO
BACKGROUND: A systematic research was performed to review the relationship between use of histamine-1 receptor antagonists and cancer risk. METHOD: Databases were searched up to December 2021. Case-control and cohort studies evaluating the relationship between use of histamine-1 receptor antagonists and risk of cancer were selected. The major outcome was cancer risk. Odds ratio (OR) with 95% confidence intervals (CIs) was calculated. Subgroup, cumulative, and sensitivity analysis and Egger test were performed. RESULTS: Five case-controls and one cohort study were included. According to cohort study, use of antihistamines were not associated with cancer risk (RR = 0.92, 95% CI = (0.78-1.07). In case-controls, the frequency of antihistamine use in cases and controls was 11.28% and 14.82% respectively which was associated with decreased cancer risk (p value = 0.02, OR = 0.93, 95%CI = (0.87, 0.99)). Sensitivity analysis showed a change in direction of pooled OR by omitting some studies. Sub-group analysis according to type of cancer showed a decrease in cancer risk in antihistamine users in glioma (p value = 0.03). CONCLUSION: Antihistamines might reduce the risk of certain cancers. More studies with defined background of allergy are needed which can clarify the relevancy of different types of cancer with anti-H1 receptors.
Assuntos
Glioma , Histamina , Humanos , Estudos de Coortes , Antagonistas dos Receptores Histamínicos H1 , Antagonistas dos Receptores HistamínicosRESUMO
Doxorubicin (DOX) is widely used in the treatment of various cancers, increasing the great risk of adverse cardiovascular events, while the clinical intervention effect is not ideal. Histamine has been documented to participate in pathophysiological processes of cardiovascular diseases and inflammation-associated carcinogenesis. However, the potential roles of histamine in antitumor-related cardiotoxicity have not been fully elucidated. In this study, cardiomyocytes (hiPSC-CMs, HL-1 cells) and mice were treated with DOX to establish DOX-induced cardiotoxicity (DIC) models. Histidine decarboxylase knockout mice (HDC-/-) mice and histamine 1 receptor (H1R) antagonist were used to explore the effect of histamine/H1R signaling on DIC. Our results demonstrated that histamine deficiency or pharmaceutical inhibition of H1R accelerated myocardial ferroptosis, which is responsible for the aggravated DIC both in vivo and in vitro, while the supplementation of exogenous histamine reversed these changes. Our data revealed that the dysfunction of histamine/H1R signaling repressed the activation of transducer and activator of transcription 3 (STAT3), accompanying with decreased expression of solute carrier family7member11 (SLC7A11), a major modulator of ferroptosis. Conclusively, the disruption of histamine/H1R axis triggered ferroptosis and exacerbated DIC possibly by modulating STAT3-SLC7A11 pathway. Our findings point to a potential therapeutic target for DIC and provide more consideration on the usage of antihistamine drugs.
Assuntos
Ferroptose , Histamina , Animais , Cardiotoxicidade/genética , Doxorrubicina/metabolismo , Doxorrubicina/toxicidade , Ferroptose/genética , Histamina/metabolismo , Histamina/farmacologia , Antagonistas dos Receptores Histamínicos/metabolismo , Antagonistas dos Receptores Histamínicos/farmacologia , Antagonistas dos Receptores Histamínicos H1/farmacologia , Histidina Descarboxilase/metabolismo , Histidina Descarboxilase/farmacologia , Camundongos , Camundongos Knockout , Miócitos Cardíacos/metabolismo , Preparações Farmacêuticas/metabolismoRESUMO
BACKGROUND: Chronic spontaneous urticaria (CSU) is a common skin disease and has a significant impact on patients' quality of life. The aim of treatment is complete symptom control. AIM: To identify potential factors associated with antihistamine-refractory isolated CSU and to determine the factors that predict response to second-generation H1 antihistamines at dosages from one- to fourfold. METHODS: We conducted a retrospective cohort study, which included adult patients diagnosed with isolated CSU and had complete symptom control. Clinical and laboratory findings were compared between the patients who were responsive to second-generation H1 antihistamines (< fourfold) and those who were refractory to a fourfold dose. Clinical and laboratory data were compared by dosage in the antihistamine-responsive group. RESULTS: There were 182 isolated CSU patients who met the study criteria, of whom 150 (82.4%) were responsive to treatment with up to a fourfold dose of second-generation H1 antihistamines, while 32 (17.6%) were refractory. In univariate analysis, age at onset, body mass index, baseline Urticaria Activity Score-7 (UAS7), white blood cell count, total neutrophil count, neutrophil-lymphocyte ratio, platelet count, and new generation antihistamines were significantly higher in the antihistamine-refractory group. According to multivariate analysis, baseline UAS7 was the only independent factor associated with antihistamine-refractory isolated CSU (odds ratio 1.14, 95% CI 1.01-1.28, P = .03). In the antihistamine-responsive group, white blood cell count tended to predict response to antihistamine treatment (P < .001, 0.04, 0.34 between onefold and twofold, twofold and threefold, and threefold and fourfold, respectively). CONCLUSION: Baseline UAS7 was an independent factor associated with antihistamine-refractory isolated CSU.
Assuntos
Urticária Crônica , Urticária , Adulto , Humanos , Urticária Crônica/tratamento farmacológico , Qualidade de Vida , Estudos Retrospectivos , Doença Crônica , Urticária/diagnóstico , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Antagonistas dos Receptores Histamínicos/uso terapêutico , Resultado do TratamentoRESUMO
A simple, rapid, sensitive and specific LC-MS/MS method was developed and validated for the quantitative determination of doxylamine in human plasma, using isotope doxylamine-d5 as internal standard (IS). The detection was conducted on a QTRAP 5500 tandem mass spectrometer coupled with electrospray ionization (ESI) source in positive ion mode. Quantification was achieved by positive electrospray ionization containing multiple reaction monitoring (MRM) transitions of m/z 271.0â182.0 for doxylamine and m/z 276.2â187.3 for IS. The mobile phase A was methanol, and mobile phase B was 20 mM ammonium acetate (0.2 % formic acid) in water, using a gradient elution procedure at a flow rate of 0.6 mL/min. The method was validated with a sensitivity of 0.500 ng/mL and a linear concentration range of 0.500-200 ng/mL. The inter-batch precision (%CV) was less than 5.4 %, and the accuracy deviation (%RE) ranged from - 10.6 % to 3.7 %; the inter-batch precision (%CV) was less than 6.6 %, and the accuracy deviation (%RE) was ranged from - 2.7 % to 0.1 %. The selectivity, sensitivity, extraction recovery, matrix effect, carryover, dilution reliability, stability and other characteristics were within the acceptable range. This validated method was successfully applied to a bioequivalence study that orally administered 25 mg of doxylamine succinate tablets in 60 healthy Chinese volunteers.
Assuntos
Doxilamina/sangue , Doxilamina/farmacocinética , Antagonistas dos Receptores Histamínicos H1/sangue , Antagonistas dos Receptores Histamínicos H1/farmacocinética , Espectrometria de Massas em Tandem/métodos , Administração Oral , China , Cromatografia Líquida/métodos , Doxilamina/administração & dosagem , Voluntários Saudáveis , Antagonistas dos Receptores Histamínicos H1/administração & dosagem , Humanos , Metanol , Reprodutibilidade dos Testes , Espectrometria de Massas por Ionização por Electrospray , Comprimidos , Equivalência TerapêuticaRESUMO
A urticária crônica é uma condição que afeta mais de um milhão de brasileiros, com grande impacto na qualidade de vida. Mesmo com diretrizes bem difundidas para o seu diagnóstico e tratamento, seu manejo pode ser desafiador em pacientes pediátricos, idosos e gestantes. Para auxiliar o médico especialista nestes casos, o Departamento Científico de Urticária da Associação Brasileira de Alergia e Imunologia elaborou esta revisão com as principais dúvidas e dificuldades referentes ao tema nestes grupos de pacientes.
Chronic urticaria is a condition that affects more than a million Brazilians with a significant impact on quality of life. Although there are well-established guidelines for diagnosis and treatment, the management of chronic urticaria may be challenging in pediatric, older, and pregnant patients. With the purpose of helping specialists manage these cases, the Urticaria Scientific Department of the Brazilian Association of Allergy and Immunology prepared this review with the most common doubts and difficulties about this topic in those patient groups.
Assuntos
Humanos , Gravidez , Lactente , Pré-Escolar , Criança , Idoso , Idoso de 80 Anos ou mais , Gestantes , Diagnóstico Diferencial , Omalizumab , Urticária Crônica , Antagonistas dos Receptores Histamínicos H1 , Pacientes , Médicos , Qualidade de Vida , Sociedades Médicas , Terapêutica , Urticária , Lactação , Diagnóstico , Alergia e Imunologia , AngioedemaRESUMO
A urticária aguda é uma causa frequente de consulta com alergistas, caracterizada por urticas e/ou angioedema. Embora autolimitada e benigna, pode causar desconforto significativo e raramente representar uma doença sistêmica grave ou reação alérgica com risco de vida. Nesta revisão, elaborada pelo Departamento Científico de Urticária da Associação Brasileira de Alergia e Imunologia, foram abordadas as principais questões referentes ao tema para auxiliar o médico especialista e generalista.
Acute urticaria is a frequent cause of consultations with allergists, being characterized by wheals and/or angioedema. Although self-limited and benign, it may cause significant discomfort and uncommonly represent a serious systemic disease or life-threatening allergic reaction. In this review prepared by the Urticaria Scientific Department of the Brazilian Association of Allergy and Immunology, the main questions about this topic are addressed to help specialists and general practitioners.
Assuntos
Humanos , Urticária , Epinefrina , Hipersensibilidade a Leite , Hipersensibilidade a Ovo , Hipersensibilidade a Drogas , Hipersensibilidade a Frutos do Mar , Hipersensibilidade a Nozes e Amendoim , Antagonistas dos Receptores Histamínicos H1 , Anafilaxia , Picada de Aranha , Médicos , Sociedades Médicas , Terapêutica , Anti-Inflamatórios não Esteroides , Síndrome de Sweet , Dermatite Alérgica de Contato , Corticosteroides , Síndrome Hipereosinofílica , Síndrome de Schnitzler , Mastocitose Cutânea , Diagnóstico , Alergia e Imunologia , Eritema , Angioedemas Hereditários , Hipersensibilidade Alimentar , Alergistas , Hipersensibilidade , AngioedemaRESUMO
AIMS: The aim of this study is to investigate the rates of hypersensitivity reactions (HSRs) in patients receiving paclitaxel chemotherapy, with and without a histamine-2 (H2 ) antagonists. METHOD: This prospective, multi-centre, cohort study compared patients receiving paclitaxel treated with premedication regimens containing chlorphenamine, dexamethasone and an H2 antagonist vs patients treated without an H2 antagonist. Rates of HSRs were described and logistic multivariable regression was used to investigate any associations with H2 antagonist treatment, adjusting for confounding variables. RESULTS: A total of 1043 individuals were included in the study; of these, 638 (61%) patients received an H2 antagonist and 405 (49%) were not given an H2 antagonist. Incidence of HSR in the cohort treated with H2 antagonists was 11.31% (n = 70) vs 9.86% (n = 41) in the cohort without. There was no statistically significant difference between the rates of HSR observed in those receiving and not receiving an H2 antagonist (odds ratio 1.04, 95% CI 0.65, 1.66, P = .9). CONCLUSIONS: Results presented within the study are consistent with other recently published evidence to suggest that H2 antagonists do not confer any advantage as part of premedication regimens in reducing the incidence of HSR in patients treated with paclitaxel.
Assuntos
Antineoplásicos Fitogênicos , Hipersensibilidade a Drogas , Antineoplásicos Fitogênicos/efeitos adversos , Estudos de Coortes , Dexametasona/uso terapêutico , Hipersensibilidade a Drogas/etiologia , Histamina , Antagonistas dos Receptores Histamínicos H1/efeitos adversos , Antagonistas dos Receptores H2 da Histamina/uso terapêutico , Humanos , Paclitaxel/efeitos adversos , Pré-Medicação/efeitos adversos , Pré-Medicação/métodos , Estudos ProspectivosRESUMO
INTRODUCTION: Osimertinib is an approved therapy for patients with a Thr790met (T790M) mutation diagnosed with non-small cell lung cancer (NSCLC) that progresses during epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy. However, in 7-13% of patients, drug-related side effects lead to discontinuation of osimertinib treatment. In such cases, osimertinib desensitization is a treatment option that can be considered. CASE REPORT: A 59-year-old female patient, who was followed up with the diagnosis of stage 4 NSCLC, was consulted to the allergy clinic because of urticaria. The patient developed urticaria plaques 20â h after the third dose of osimertinib tablet. MANAGEMENT & OUTCOME: With the diagnosis of osimertinib-induced urticaria, desensitization was planned for the patient. Treatment was started with a dose of 0.1â mg/day osimertinib. The procedure was completed in approximately 50 days, and a dose of 80â mg/day was reached with antihistamine suppression. DISCUSSION: Here, a successful osimertinib desensitization in a patient with a history of osimertinib-related type 1 allergic reaction is reported. Osimertinib desensitization is a treatment option that should be considered in cases where treatment has to be ceased due to drug-related side effects.
Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Urticária , Acrilamidas , Compostos de Anilina/efeitos adversos , Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Feminino , Antagonistas dos Receptores Histamínicos/uso terapêutico , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Humanos , Indóis , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Pessoa de Meia-Idade , Mutação , Inibidores de Proteínas Quinases/efeitos adversos , Pirimidinas , Urticária/induzido quimicamenteRESUMO
Since 1955, the only available H1 antihistamines for intravenous administration have been first-generation formulations and, of those, only intravenously administered (IV) diphenhydramine is still approved in the USA. Orally administered cetirizine hydrochloride, a second-generation H1 antihistamine, has been safely used over-the-counter for many years. In 2019, IV cetirizine was approved for the treatment of acute urticaria. In light of this approval, this narrative review discusses the changing landscape of IV antihistamines for the treatment of histamine-mediated conditions. Specifically, IV antihistamines will be discussed as a treatment option for acute urticaria and angioedema, as premedication to prevent infusion reactions related to anticancer agents and other biologics, and as an adjunct treatment for anaphylaxis and other allergic reactions. Before the development of IV cetirizine, randomized controlled trials of IV antihistamines for these indications were lacking. Three randomized controlled trials have been conducted with IV cetirizine versus IV diphenhydramine in the ambulatory care setting. A phase 3 trial of IV cetirizine 10 mg versus IV diphenhydramine 50 mg was conducted in 262 adults who presented to the urgent care/emergency department with acute urticaria requiring antihistamines. For the primary efficacy endpoint, defined as change from baseline in a 2-h patient-rated pruritus score, non-inferiority of IV cetirizine to IV diphenhydramine was demonstrated (score - 1.6 vs - 1.5, respectively; 95% CI - 0.1, 0.3). Compared with IV diphenhydramine, IV cetirizine demonstrated fewer adverse effects including less sedation, a significantly shorter length of stay in the treatment center, and fewer returns to the treatment center at 24 and 48 h. Similar findings were demonstrated in another phase 2 acute urticaria trial and in a phase 2 trial assessing IV cetirizine for pretreatment for infusion reactions in the oncology/immunology setting. IV cetirizine is associated with similar patient outcomes, fewer adverse effects, and increased treatment center efficiency than IV diphenhydramine.
Assuntos
Cetirizina , Urticária , Administração Intravenosa , Adulto , Cetirizina/efeitos adversos , Difenidramina/efeitos adversos , Antagonistas dos Receptores Histamínicos H1/efeitos adversos , Humanos , Urticária/induzido quimicamente , Urticária/tratamento farmacológicoRESUMO
BACKGROUND: Chronic urticaria (CU) is a debilitating mast cell-driven disease, often refractory to standard therapy (ie, antihistamines). Lirentelimab, an anti-sialic acid-binding immunoglobulin-like lectin 8 mAb, selectively inhibits mast cells and depletes eosinophils. OBJECTIVE: We sought to determine safety and efficacy of lirentelimab in patients with CU. METHODS: This phase 2a study enrolled patients with CU refractory to up to 4-fold H1-antihistamine doses. Patients received 6 monthly intravenous doses of lirentelimab (0.3, 1, and up to 3 mg/kg). Primary efficacy end point was change in Urticaria Control Test score at week 22. Urticaria Activity Score weekly average (UAS7) was assessed in patients with chronic spontaneous urticaria (CSU), and Cholinergic UAS7 was used for patients with cholinergic urticaria (CholU). RESULTS: A total of 45 patients were enrolled in 4 cohorts (n = 13 omalizumab-naive CSU, n = 11 omalizumab-refractory CSU, n = 11 CholU, n = 10 symptomatic dermographism). Urticaria Control Test scores increased with lirentelimab across cohorts, with mean changes at week 22 of 11.1 ± 4.1, 4.8 ± 7.0, 6.5 ± 6.2, and 3.4 ± 4.1 and complete response rates (Urticaria Control Test score ≥ 12) of 92%, 36%, 82%, and 40%, respectively. In omalizumab-naive and omalizumab-refractory patients with CSU, disease activity decreased at week 22 (mean UAS7 change, -73% and -47%, respectively), with UAS7 response rates (≥50% reduction) of 77% and 45%, respectively. In patients with symptomatic dermographism, 50% (5 of 10) and 40% (4 of 10) had complete itch and hive resolution by FricTest, respectively, and 100% (7 of 7) evaluable patients with CholU had negative responses to Pulse-Controlled Ergometry exercise test. Most common adverse events included infusion-related reactions (43%; all mild/moderate and transient), nasopharyngitis (21%), and headache (19%). No treatment-related serious adverse events occurred. CONCLUSIONS: Lirentelimab demonstrated activity across 3 forms of antihistamine-refractory CU.