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3.
Int Arch Allergy Immunol ; 181(1): 24-30, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31752003

RESUMO

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) represent one of the most prevalent causes of drug hypersensitivity reactions (DHRs), yet the underlying processes are far from clear. Despite the established role of histamine in allergic reactions, its precise implication in DHRs is elusive. OBJECTIVES: This study aimed to explore the connection of basal blood histamine levels to the reported NSAID hypersensitivity. METHODS: Sixteen patients reporting hypersensitivity reactions to a single or multiple NSAIDs and/or paracetamol and 18 healthy volunteers serving as the normal control group enrolled in the study. The medical history was recorded and histamine was quantified spectrophotofluorometrically in whole peripheral blood and plasma. RESULTS: Compared to the normal group, plasma but not whole blood histamine levels were significantly higher in patients (p < 0.001), mainly in the subgroup reporting hypersensitivity to a single agent (p < 0.001). Plasma histamine levels were significantly correlated with the culprit drug selectivity for cyclooxygenase (COX) isozymes (p < 0.001), with higher levels being obtained in patients reporting reactions to COX-1 than to COX-2 selective inhibitors (p < 0.05). CONCLUSIONS: The findings provide first evidence connecting basal blood histamine levels to the reported NSAID-triggered DHRs. Prospective studies are expected to decipher the contribution of histamine-associated parameters to the mechanisms underlying DHRs.


Assuntos
Acetaminofen/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Hipersensibilidade a Drogas/imunologia , Histamina/sangue , Acetaminofen/imunologia , Acetaminofen/uso terapêutico , Adulto , Idoso , Alérgenos/imunologia , Anti-Inflamatórios não Esteroides/imunologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Biomarcadores/sangue , Inibidores de Ciclo-Oxigenase 2/imunologia , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Autorrelato , Adulto Jovem
4.
Cardiovasc Pathol ; 44: 107154, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31760242

RESUMO

Although the cause of eosinophilic coronary periarteritis (ECPA) remains unclear, an allergic background is present in fewer patients than expected. A 50-year-old man with no history of allergy or symptoms suggestive of cardiac or respiratory disorders suddenly died shortly after oral administration of loxoprofen sodium. Autopsy showed eosinophilic coronary periarteritis in three main branches of the coronary arteries, characterized by eosinophil-predominant inflammation without fibrinoid necrosis or granulomatous change in the adventitia and its surroundings of the three main branches of the coronary arteries, in addition to the localized sign of bronchial asthma in the lung. Immunohistochemical examination showed that many mast cells positive for human mast cell tryptase were evident in the perivascular tissue containing peripheral nerve trunks. Whereas the blood concentration of loxoprofen sodium was within the therapeutic range, significant elevation of the serum histamine and tryptase levels was found. The present case suggests that eosinophilic coronary periarteritis may be caused by a type I allergic reaction in some patients and that loxoprofen sodium can trigger a life-threatening type I allergic reaction, including eosinophilic coronary periarteritis, leading to sudden unexpected death.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Doença da Artéria Coronariana/induzido quimicamente , Vasos Coronários/efeitos dos fármacos , Morte Súbita Cardíaca/etiologia , Hipersensibilidade a Drogas/etiologia , Eosinofilia/induzido quimicamente , Fenilpropionatos/efeitos adversos , Dor de Ombro/tratamento farmacológico , Autopsia , Causas de Morte , Doença da Artéria Coronariana/imunologia , Doença da Artéria Coronariana/patologia , Vasos Coronários/imunologia , Vasos Coronários/patologia , Morte Súbita Cardíaca/patologia , Hipersensibilidade a Drogas/imunologia , Hipersensibilidade a Drogas/patologia , Eosinofilia/imunologia , Eosinofilia/patologia , Evolução Fatal , Humanos , Masculino , Mastócitos/efeitos dos fármacos , Mastócitos/imunologia , Mastócitos/patologia , Pessoa de Meia-Idade
8.
Immunogenetics ; 71(10): 605-615, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31776588

RESUMO

Immunogenicity of biomolecules is one of the largest concerns in biological therapeutic drug development. Adverse immune responses as a result of immunogenicity to biotherapeutics range from mild hypersensitivity reactions to potentially life-threatening anaphylactic reactions and can negatively impact human health and drug efficacy. Numerous confounding patient-, product- or treatment-related factors can influence the development of an immune reaction against therapeutic proteins. The goal of this study was to investigate the relationship between pre-existing drug reactivity (PE-ADA), individual immunogenetics (MHC class II haplotypes), and development of treatment-induced antidrug antibodies (TE-ADA) in cynomolgus macaque. PE-ADA refers to the presence of antibodies immunoreactive against the biotherapeutic in treatment-naïve individuals. We observed that PE-ADA frequency against four different bispecific antibodies in naïve cynomolgus macaque is similar to that reported in humans. Additionally, we report a trend towards an increased incidence of TE-ADA development in macaques with high PE-ADA levels. In order to explore the relationship between MHC class II alleles and risk of ADA development, we obtained full-length MHC class II sequences from 60 cynomolgus macaques in our colony. We identified a total of 248 DR, DP, and DQ alleles and 236 unique haplotypes in our cohort indicating a genetically complex set of animals potentially reflective of the human population. Based on our observations, we propose the evaluation of the magnitude/frequency of pre-existing reactivity and consideration of MHC class II genetics as additional useful tools to understand the immunogenic potential of biotherapeutics.


Assuntos
Anticorpos Biespecíficos/imunologia , Hipersensibilidade a Drogas/imunologia , Genes MHC da Classe II/genética , Genes MHC da Classe II/imunologia , Imunogenética , Animais , Anticorpos Biespecíficos/administração & dosagem , Anticorpos Biespecíficos/sangue , Hipersensibilidade a Drogas/genética , Frequência do Gene , Haplótipos , Macaca fascicularis , Masculino , Filogenia
10.
Niger Postgrad Med J ; 26(4): 195-198, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31621657

RESUMO

Background: The presence of human leukocyte antigen (HLA) B*57:01 allele predicts hypersensitivity reaction (HSR) to abacavir (ABC), a nucleoside reverse-transcriptase inhibitor used for human immunodeficiency virus (HIV) treatment. However, the prevalence of this allele amongst Nigerians with HIV is yet to be established. We aimed to determine the prevalence of HLA-B*57:01 allele amongst Nigerians with HIV infection. Methods: We conducted a multicentre cross-sectional epidemiologic survey. Between April 2016 and April 2017, patients were enrolled across five HIV treatment facilities in Nigeria. Participants' demographic information and their history of ABC exposure were obtained, and venous blood was obtained for HLA typing. Results: One thousand five hundred and four (1504) adults were enrolled, with a mean age of 44.6 ± 10.7 years, 1078 (71.7%) were female. 1463 (97.3%) were on antiretroviral therapy. ABC use was reported by 12 (0.8%) participants and none reported HSR. Of 1500 blood samples that were processed, 1458 (97.2%) were successfully typed. Of these, 132 (9.1%) were HLA-B*57 positive using non-specific low-resolution HLA-B*5701 primer mix. On further analysis, none of the 132 samples (0%) had the HLA-B*5701 allele. Conclusion: HLA-B*5701allele is rare amongst Nigerians.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Didesoxinucleosídeos/uso terapêutico , Hipersensibilidade a Drogas/imunologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Antígenos HLA-B/genética , Inibidores da Transcriptase Reversa/uso terapêutico , Adulto , Grupo com Ancestrais do Continente Africano/genética , Idoso , Estudos Transversais , Didesoxinucleosídeos/efeitos adversos , Hipersensibilidade a Drogas/epidemiologia , Hipersensibilidade a Drogas/genética , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/genética , Antígenos HLA-B/sangue , Antígenos HLA-B/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Nigéria/epidemiologia , Prevalência , Inibidores da Transcriptase Reversa/efeitos adversos
11.
Int Immunopharmacol ; 75: 105800, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31401386

RESUMO

Iopamidol is a radiographic contrast media which caused a very high incidence of anaphylactic reactions. Mast cells are sentinel cells in host defense reactions during immediate hypersensitivity responses and anaphylactic responses. Mas-related G protein-coupled receptor X2 (MRGPRX2) is a kind of mast cell specific receptor, which triggers mast cell degranulation in anaphylactic reactions. Mice MrgprB2 is a homologous gene of MRGPRX2. We sought to better understand the anaphylactic reactions induced by Iopamidol and the mechanisms involving MRGPRX2. The MRGPRX2-related anaphylactic reactions induced by Iopamidol were investigated using the hindpaw swelling and extravasation assay in vivo and a calcium imaging assay was used for mast cell intracellular calcium responses detection and mast cell release of anaphylactic mediators, such as ß-hexosaminidase, histamine and TNF-α, was also detected in vitro. The mast cell deficient KitW-sh/W-sh mice and MrgprB2 knockout mice exhibited a reduced Iopamidol-induced inflammation effect compared with wild type mice. Furthermore, human mast cells that express MRGPRX2 were activated by Iopamidol in a dose-dependent manner, meanwhile MRGPRX2 knockdown mast cells showed reduced intracellular calcium responses and anaphylactic mediators release effect. It could be concluded that Iopamidol-induced anaphylactoid reactions were MRGPRX2 mediated to provoke mast cells Ca2+ mobilization and degranulation.


Assuntos
Hipersensibilidade a Drogas/imunologia , Iopamidol , Mastócitos/imunologia , Anafilaxia Cutânea Passiva/imunologia , Receptores Acoplados a Proteínas-G/imunologia , Animais , Cálcio/imunologia , Linhagem Celular , Humanos , Imunoglobulina E , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores Acoplados a Proteínas-G/genética , Fator de Necrose Tumoral alfa/imunologia
12.
Int Arch Allergy Immunol ; 180(2): 103-112, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31394524

RESUMO

Within the broad category of adverse drug reactions in children, there has been a recent focus specifically on the evaluation of children with antibiotic allergy, in particular, beta-lactam allergy. The potential consequences of being labeled beta-lactam allergy are increasingly recognized. Appropriate evaluation of children with suspected reactions to antibiotics is essential as it is increasingly being recognized that the label of "penicillin allergy" is associated with adverse health and economic outcomes. This review will focus on the 3 main classes of antibiotics reported to cause allergic reactions in children: beta lactams (penicillin derivatives and cephalosporins), macrolides, and sulfonamides. This article is a narrative review of the prevalence, diagnosis, and management of different types of antibiotic allergies in children. Our review reveals that antibiotic allergy is often overreported and not appropriately diagnosed in the pediatric age groups. There is a recent shift in the diagnostic paradigm from the use of skin tests and if negative challenges to the use of challenge only in the pediatric age group. Larger studies to establish the usefulness and safety of this new approach as well as updated guidelines are needed.


Assuntos
Hipersensibilidade a Drogas/imunologia , Macrolídeos/imunologia , Testes Cutâneos/métodos , Sulfonamidas/imunologia , beta-Lactamas/imunologia , Anafilaxia/imunologia , Criança , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/epidemiologia , Humanos , Lactente
13.
Pediatr Hematol Oncol ; 36(5): 277-286, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31296092

RESUMO

Asparaginase is an important component of multi-agent chemotherapy for the treatment of pediatric acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LLy). Hypersensitivity to the PEGylated form, pegaspargase, is the most common toxicity observed and is ideally addressed by substituting multiple doses of erwinia asparaginase for each subsequent dose of pegaspargase. An international shortage of erwinia asparaginase has limited the therapeutic options for those experiencing pegaspargase hypersensitivity. Here, we report pegaspargase can be safely administered, while maintaining sustained levels of asparaginase activity, to patients who have had a prior hypersensitivity reaction to pegaspargase by using a standard rapid desensitization protocol. Ten patients with prior hypersensitivity reactions to pegaspargase were treated by using a standardized rapid desensitization protocol. Eight patients had therapeutic asparaginase levels between days 4 and 7 of ≥0.05 IU/mL, and seven patients continued to have sustained levels above ≥0.1 IU/mL between days 10 and 14. Based on chemotherapy regimens, five of these patients successfully received more than one dose of pegaspargase utilizing this protocol.


Assuntos
Asparaginase , Proteínas de Bactérias , Dessensibilização Imunológica , Hipersensibilidade a Drogas/prevenção & controle , Polietilenoglicóis , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Adulto , Asparaginase/administração & dosagem , Asparaginase/efeitos adversos , Asparaginase/imunologia , Proteínas de Bactérias/administração & dosagem , Proteínas de Bactérias/efeitos adversos , Proteínas de Bactérias/imunologia , Criança , Pré-Escolar , Hipersensibilidade a Drogas/imunologia , Escherichia coli/enzimologia , Feminino , Humanos , Masculino , Pectobacterium chrysanthemi/enzimologia , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia
17.
Ann Allergy Asthma Immunol ; 123(1): 48-56.e1, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31108181

RESUMO

BACKGROUND: Severe hypersensitivity reactions (HSRs) interfere with the administration of necessary drugs for patients; drug desensitization can be a good alternative strategy. Although rapid drug desensitization (RDD) has been shown to be safe and effective, some patients still experience breakthrough reactions (BTRs) during desensitization. OBJECTIVE: We aimed to estimate clinical outcomes of RDD and to identify risk factors for BTR. METHODS: From January 2015 to December 2017, retrospective analysis was done in cancer patients with HSRs to chemotherapy and monoclonal antibody who underwent 3-bag, 12-step RDD in Asan Medical Center. RESULTS: A total of 58 patients (42 females; mean age, 54.7 ± 11.0) underwent 234 desensitization procedures. The most common underlying malignancy was gynecologic cancer (n = 26, 44.8%), and platinum-based drugs were common target drugs (135 cases of 36 patients). Twenty-six of 58 patients (44.8%) experienced 56 BTRs, whereas 178 cases (76.1%) of total desensitization did not show any reactions. Among them, 12 patients (20.7%) had moderate BTRs requiring systemic steroids, and 3 (5.1%) experienced severe BTRs requiring epinephrine administration. Logistic regression analysis revealed more severe initial HSRs (OR = 17.94, 95% CI = 1.78-181.68, P = .015), drug allergy history (OR = 7.83, 95% CI = 1.48-41.44, P = .035), and frequency of exposure to the chemotherapeutic agents (OR = 1.14, 95% CI = 1.01-1.28, P = .016) increased the risk of moderate to severe BTR. CONCLUSION: The standardized 12-step protocol for RDD was effective and safe for most patients. Severity of initial HSR, history of drug allergy, and previous high exposure to the chemotherapeutic agent showed a positive correlation with BTR above moderate grade. Studies are needed to propose an individualized protocol according to patient-specific risk assessment.


Assuntos
Antineoplásicos/efeitos adversos , Antineoplásicos/imunologia , Hipersensibilidade a Drogas/tratamento farmacológico , Hipersensibilidade a Drogas/imunologia , Antineoplásicos/uso terapêutico , Dessensibilização Imunológica/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Testes Cutâneos/métodos
19.
Br J Anaesth ; 123(1): e144-e150, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30961915

RESUMO

BACKGROUND: Following diagnosis of neuromuscular blocking agent (NMBA) anaphylaxis, identifying safe alternatives for subsequent anaesthesia is critical. A patient with anaphylaxis to one NMBA can also have an allergic reaction to other NMBAs (cross-reactivity). Whilst drug provocation testing is standard for identifying or excluding allergy, there is significant risk. In vitro, after an allergen activates basophils, basophils express surface activation markers that can be measured by basophil activation testing (BAT). We compared cross-reactivity between NMBAs assessed by BAT against that by skin testing. METHODS: All patients attending an anaesthetic allergy clinic in Sydney, Australia between May 2017 and July 2018 diagnosed with NMBA anaphylaxis qualified for this study comparing intradermal skin tests and BAT with a panel of NMBAs (rocuronium, vecuronium, pancuronium, suxamethonium, cisatracurium). RESULTS: Of the 61 patients participating, sensitisation on skin testing and on BAT completely matched in only nine patients (15%). Sensitisation was not in agreement for pancuronium, cisatracurium and rocuronium, but was in agreement for vecuronium and suxamethonium. Nine patients with negative skin tests subsequently tolerated cisatracurium, and one false positive on BAT to cisatracurium was detected. CONCLUSIONS: The utility of BAT in identifying safe NMBAs for subsequent anaesthesia needs further evaluation. BAT detects a different cross-reactivity profile to skin tests. Negative skin testing and BAT might increase confidence in performing drug provocation testing, but this and follow-up of subsequent anaesthesia in our cohort is necessary to determine the clinical significance of BAT sensitisation.


Assuntos
Anafilaxia/imunologia , Basófilos/imunologia , Hipersensibilidade a Drogas/imunologia , Bloqueadores Neuromusculares/imunologia , Testes Cutâneos/estatística & dados numéricos , Adolescente , Adulto , Idoso , Austrália , Reações Cruzadas/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Cutâneos/métodos , Adulto Jovem
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