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1.
Ann Pharmacother ; 57(1): 55-61, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35570798

RESUMO

BACKGROUND: Hypersensitive reactions (HSRs) often require that the provoking medication be discontinued but chemotherapeutic drugs are often essential for the treatment of the disease. Rapid drug desensitization is a procedure that induces temporary tolerance to the drug allowing continuation of treatment in patients who have presented HSRs. Most of the desensitization protocols use 3 bags with sequential dilutions of the drug, which are infused in gradual steps. However, it has not been sufficiently investigated whether dilution is essential for successful desensitization. OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of a new one-bag desensitization protocol which uses a single solution of 1 mg/mL throughout the procedure allowing to reduce time and simplifying the desensitization procedure. METHODS: Retrospective observational study was carried out in adult patients with HSRs to chemotherapy agents who received a new nondilution one-bag desensitization protocol between 2016 and 2021. RESULTS: A total of 130 desensitization procedures with an undiluted one-bag protocol were performed on 17 patients with HSRs to chemotherapy. One hundred and seven (82.3%) were for desensitization to CBDCA, 15 (11.5%) for oxaliplatin, 4 (3.1%) for paclitaxel and 4 (3.1%) for brentuximab. All of the 130 procedures were successfully accomplished, and all patients could receive their target dose. No breakthrough reactions (BTRs) occurred in 77% (100/130) of desensitizations, and only mild reactions (grade 1) with skin symptoms were observed in 23% (30/130) of desensitizations. CONCLUSION AND RELEVANCE: The undiluted one-bag desensitization protocol was safe and effective and has been adopted as the standard of care at our institution in treating patients with HSRs to chemotherapeutic drugs as it requires less time and simplifies the desensitization procedure, optimizing risk management.


Assuntos
Antineoplásicos , Hipersensibilidade a Drogas , Adulto , Humanos , Carboplatina/efeitos adversos , Oxaliplatina/uso terapêutico , Hipersensibilidade a Drogas/etiologia , Antineoplásicos/uso terapêutico , Dessensibilização Imunológica/métodos , Paclitaxel/uso terapêutico , Estudos Observacionais como Assunto
3.
Medicine (Baltimore) ; 101(45): e31726, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36397338

RESUMO

Epithelial Ovarian cancer (EOC) is the most lethal gynecologic cancer worldwide. Carboplatin (CP) is the main chemotherapeutic agent in the treatment of ovarian cancer. However, the development of a hypersensitivity reaction (HSR) in 10% to 15% of patients with EOC is an important limiting factor for the clinical use of CP. Herein, we aimed to investigate the efficacy and safety of CP-desensitization (CP-D) therapy in the treatment of recurrent patients with EOC. Forty-seven ovarian cancer cases treated with CP-desensitization at the Istanbul University Oncology Institute were retrospectively analyzed between 01.01.2017 and 01.01.2022. The decision for CP-D was based on the patients' history of HSR and/or a positive skin test. For all patients, a 6-hour 12-step rapid drug desensitization protocol with a 30-minutes premedication regimen was used. Forty-seven patients were included in this study, and the median age at diagnosis was 53 years (range; 27-80). Twenty-one (43.7%) patients had 1 or more comorbid diseases, and 12.7% had a previous history of drug allergy. On average, HSR due to carboplatin was identified after 9 (7-16) cycles, and carboplatin was administered n = 11 (range, 3-36) times to patients. The overall survival from the first desensitization procedure (0S2) was 42.2 months (range: 25.3-59.1), and the 1-, 2-, and 5-years survival rates were 92.6%, 75.6%, and 47.2%, respectively. The objective response rate (ORR) was 78.5%. Cumulatively, 496 CP-D procedures were performed, of which 478 (96.3%) were successfully completed. None of the patients included in this study developed severe (grade 3-4) HSR during CP administration (no adrenaline was used, no need for intensive care). No deaths due to CP-D were noted. CP-D is a beneficial and safe method in treating platinum-sensitive recurrent EOC patients with CP-induced HSR.


Assuntos
Hipersensibilidade a Drogas , Neoplasias Ovarianas , Humanos , Feminino , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carboplatina/efeitos adversos , Estudos Retrospectivos , Dessensibilização Imunológica/métodos , Hipersensibilidade a Drogas/terapia , Hipersensibilidade a Drogas/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/induzido quimicamente , Doença Crônica
5.
J Med Case Rep ; 16(1): 407, 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36345015

RESUMO

BACKGROUND: Abacavir is a nucleoside reverse transcriptase inhibitor that is used as a component of the antiretroviral treatment regimen in the management of the human immunodeficiency virus for both adults and children. It is efficacious, but its use may be limited by a hypersensitivity reaction linked with the HLA-B*57:01 genotype. HLA-B*57:01 has been reported to be rare in African populations. Because of the nature of its presentation, abacavir hypersensitivity is prone to late diagnosis and treatment, especially in settings where HLA-B*57:01 genotyping is not routinely done. CASE REPORT: We report a case of a severe hypersensitivity reaction in a 44-year-old Kenyan female living with the human immunodeficiency virus and on abacavir-containing antiretroviral therapy. The patient presented to the hospital after recurrent treatment for a throat infection with complaints of fever, headache, throat ache, vomiting, and a generalized rash. Laboratory results evidenced raised aminotransferases, for which she was advised to stop the antiretrovirals that she had recently been started on. The regimen consisted of abacavir, lamivudine, and dolutegravir. She responded well to treatment but was readmitted a day after discharge with vomiting, severe abdominal pains, diarrhea, and hypotension. Her symptoms disappeared upon admission, but she was readmitted again a few hours after discharge in a hysterical state with burning chest pain and chills. Suspecting abacavir hypersensitivity, upon interrogation she reported that she had taken the abacavir-containing antiretrovirals shortly before she was taken ill. A sample for HLA-B*57:01 was taken and tested positive. Her antiretroviral regimen was substituted to tenofovir, lamivudine, and dolutegravir, and on subsequent follow-up she has been well. CONCLUSIONS: Clinicians should always be cognizant of this adverse reaction whenever they initiate an abacavir-containing therapy. We would recommend that studies be done in our setting to verify the prevalence of HLA-B*57:01.


Assuntos
Fármacos Anti-HIV , Hipersensibilidade a Drogas , Infecções por HIV , Adulto , Criança , Feminino , Humanos , Lamivudina/efeitos adversos , Quênia , Didesoxinucleosídeos/efeitos adversos , Infecções por HIV/tratamento farmacológico , Antirretrovirais/uso terapêutico , Vômito , Fármacos Anti-HIV/efeitos adversos , Hipersensibilidade a Drogas/etiologia
8.
Georgian Med News ; (328-329): 21-26, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36318836

RESUMO

Beta-lactam antibiotics (BLAs) can provoke drug hypersensitivity reactions, particularly delayed-type reactions. This article presents a case of drug allergy with manifestations of Stevens-Johnson syndrome (SJD) in a 42-year-old man with yersiniosis and active herpesvirus -4, -6 type, who received amoxacillin with clavulanic acid. The patient underwent a basophil activation test (BAT) for BLAs, and a positive result was found for both amoxacillin and 2nd and 3rd generation cephalosporins. On the example of a clinical case, probable pathogenetic mechanisms of the risk of the appearance of immediate-type hypersensitivity reactions in persons with active herpesvirus -4, -6 type infection are shown. The possibility of using the cellular BAT for the diagnosis of delayed-type hypersensitivity reactions and for the diagnosis of cross-reactions to antibiotics has also been demonstrated.


Assuntos
Hipersensibilidade a Drogas , Hipersensibilidade Imediata , Masculino , Humanos , Adulto , Testes Cutâneos , Antibacterianos , beta-Lactamas , Herpesvirus Humano 4 , Hipersensibilidade a Drogas/diagnóstico
12.
Allergol Immunopathol (Madr) ; 50(6): 122-127, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36335455

RESUMO

BACKGROUND: The European Network for Drug Allergy (ENDA) proposed a consensus document for hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) in 2011. A subgroup of patients with NSAIDs-exacerbated respiratory disease (NERD) develop urticaria/angioedema type reactions in response to NSAIDs. The Kalyoncu classification might be a novel option to classify patients with NSAID hypersensitivity (NH). In this study, we compare the ENDA and the Kalyoncu classifications. METHODS: This study enrolled a total of 196 patients. NH reaction types were categorized as asthma, rhinitis, urticaria/angioedema and anaphylaxis. Based on the reaction history and oral provocation test findings, patients were grouped according to ENDA and Kalyoncu classifications. RESULTS: The mean age of the 196 patients was 40.32±13.28 years, and 130 (66.3%) of them were female. Under the ENDA and Kalyoncu classifications, the most common NH subgroups were NERD (32%), and isolated NH (34.2%), the least prevalent NH subgroups were single NSAID-induced delayed reactions (SNIDR) (1.5%), and pseudo Samter's syndrome (11.7%). CONCLUSIONS: Our research revealed that the Kalyoncu classification is more descriptive of patients with NERD exhibiting urticaria/angioedema-type reactions. It also provides future risk assessment for development of NERD. For controversial cases, the Kalyoncu classification can be utilized as a new complimentary option alone or in conjunction with ENDA classification.


Assuntos
Anafilaxia , Angioedema , Hipersensibilidade a Drogas , Rinite , Urticária , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Masculino , Hipersensibilidade a Drogas/diagnóstico , Anti-Inflamatórios não Esteroides/efeitos adversos , Anafilaxia/diagnóstico , Anafilaxia/induzido quimicamente , Angioedema/diagnóstico , Urticária/diagnóstico
13.
Allergol. immunopatol ; 50(6): 122-127, 01 nov. 2022. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-211513

RESUMO

Background The European Network for Drug Allergy (ENDA) proposed a consensus document for hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) in 2011. A subgroup of patients with NSAIDs-exacerbated respiratory disease (NERD) develop urticaria/angioedema type reactions in response to NSAIDs. The Kalyoncu classification might be a novel option to classify patients with NSAID hypersensitivity (NH). In this study, we compare the ENDA and the Kalyoncu classifications. Methods This study enrolled a total of 196 patients. NH reaction types were categorized as asthma, rhinitis, urticaria/angioedema and anaphylaxis. Based on the reaction history and oral provocation test findings, patients were grouped according to ENDA and Kalyoncu classifications. Results The mean age of the 196 patients was 40.32±13.28 years, and 130 (66.3%) of them were female. Under the ENDA and Kalyoncu classifications, the most common NH subgroups were NERD (32%), and isolated NH (34.2%), the least prevalent NH subgroups were single NSAID-induced delayed reactions (SNIDR) (1.5%), and pseudo Samter’s syndrome (11.7%). Conclusions Our research revealed that the Kalyoncu classification is more descriptive of patients with NERD exhibiting urticaria/angioedema-type reactions. It also provides future risk assessment for development of NERD. For controversial cases, the Kalyoncu classification can be utilized as a new complimentary option alone or in conjunction with ENDA classification (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Anti-Inflamatórios não Esteroides/efeitos adversos , Anafilaxia/induzido quimicamente , Angioedema/induzido quimicamente , Rinite/induzido quimicamente , Urticária/induzido quimicamente , Hipersensibilidade a Drogas/diagnóstico , Anafilaxia/diagnóstico , Angioedema/diagnóstico , Urticária/diagnóstico , Rinite/diagnóstico
14.
PLoS One ; 17(11): e0277046, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36327304

RESUMO

BACKGROUND: Research on the increasing incidence of allergic diseases evidenced the role of diet as a potential key factor. Diet can modulate the low-grade systemic inflammation related to obesity and several diseases. There are no published data on drug allergy. AIM: To investigate a potential association between diet, including dietary inflammatory index (DII), and drug allergy. Also, to evaluate correlations between diet and obesity, inflammatory and metabolic parameters in patients with drug allergy. METHODS: Ninety consecutive patients studied for suspected drug allergy were evaluated in terms of dietary parameters, anthropometric measurements, bioimpedance and biochemical analysis. DII was calculated based on information collected from a food frequency questionnaire. RESULTS: After diagnostic work-up, 39 patients had confirmed drug allergy and 45 excluded, representing the study group and the control group, respectively. The majority (79%) were female, with mean age of 39.58±13.3 years. The 84 subjects revealed an anti-inflammatory diet pattern. No significative difference was found in DII scores between drug allergic patients and controls (-3.37±0.95 vs -3.39±0.86, p = 0.985). However, the patients with drug allergy revealed higher obesity and inflammatory parameters. A significative negative correlation was found between DII and adiponectin levels, in the control group (r = -0.311, p = 0.040). In the patient group, a significative positive correlation was observed between DII and triglycerides (r = 0.359, p = 0.032). No other correlations were found between DII and the assessed parameters. Patients with drug allergy presented a significative higher intake of mono-unsaturated fatty-acids comparing to controls (19.8±3.7 vs 17.8 ± 4.0, p = 0.021). No other statistically significant differences were achieved in dietary parameters, between patients and controls. CONCLUSION: The population assessed in this study revealed an anti-inflammatory diet profile. Although we have found in a previous work that the same patients with drug allergy revealed higher obesity and inflammatory parameters, the DII did not allow to distinguish between patients with drug allergy or controls. The DII scores correlated with triglycerides levels in the drug allergy patients and inversely with adiponectin levels in the control group. Larger studies are needed to clarify the potential role of the diet in drug allergy and its outcomes.


Assuntos
Adiponectina , Hipersensibilidade a Drogas , Humanos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Dieta/efeitos adversos , Inflamação/epidemiologia , Obesidade , Triglicerídeos , Fatores de Risco
15.
Front Immunol ; 13: 997389, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36341461

RESUMO

Background: Allergic drug reaction or drug allergy is an immunologically mediated drug hypersensitivity reaction (DHR). G-protein coupled receptors (GPCRs) are common drug targets and communicate extracellular signals that initiate cellular responses. Recent evidence shows that GPCR MRGPRX2 is of major importance in IgE-independent pseudo-allergic DHRs based on the suspected interactions between many FDA-approved peptidergic compounds and MRGPRX2. Objective: Our aim was to uncover novel MRGPRX2-selective and -potent agonists as drug candidates responsible for clinical features of pseudo-allergic DHRs. Methods: We conducted a primary high-throughput screening (HTS), coupled with mutagenesis targeting the MRGPRX2 N62S mutation, on a panel of 3,456 library compounds. We discovered pharmacologically active hit compounds as agonists of the MRGPRX2 protein according to high degrees of potency evaluated by the calcium response and validated by the degranulation assay. Using the molecular tool Forge, we also characterized the structure-activity relationship shared by identified hit compounds. Results: The alternative allele of single nucleotide polymorphism rs10833049 (N62S) in MRGPRX2 demonstrated loss-of-function property in response to substance P and antineoplastic agent daunorubicin hydrochloride. We applied a unique assay system targeting the N62S mutation to the HTS and identified 84 MRGPRX2-selective active hit compounds representing diverse classes according to primary drug indications. The top five highly represented groups included fluoroquinolone and non-fluoroquinolone antibiotics; antidepressive/antipsychotic; antihistaminic and antineoplastic agents. We classified hit compounds into 14 clusters representing a variety of chemical and drug classes beyond those reported, such as opioids, neuromuscular blocking agents, and fluoroquinolones. We further demonstrated MRGPRX2-dependent degranulation in the human mast cell line LAD2 cells induced by three novel agonists representing the non-fluoroquinolone antibiotics (bacitracin A), anti-allergic agents (brompheniramine maleate) and tyrosine-kinase inhibitors (imatinib mesylate). Conclusion: Our findings could facilitate the development of interventions for personalized prevention and treatment of DHRs, as well as future pharmacogenetic investigations of MRGPRX2 in relevant disease cohorts.


Assuntos
Hipersensibilidade a Drogas , Receptores de Neuropeptídeos , Humanos , Receptores de Neuropeptídeos/metabolismo , Degranulação Celular , Mastócitos , Proteínas do Tecido Nervoso , Receptores Acoplados a Proteínas G/metabolismo , Antibacterianos/farmacologia
18.
Transpl Infect Dis ; 24(5): e13955, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36254502

RESUMO

Antibiotic allergy labels (AALs) are commonly reported, with well-defined prevalence in the general population; several studies have now focused efforts on immunocompromised hosts. Understanding the prevalence of reported allergy labels and methods of antibiotic allergy evaluation and delabeling strategies has the potential to improve prescribing practices and clinical outcomes in this high-antibiotic use group. In this review, we will discuss the current literature on the prevalence, impact, and evaluations of AALs in immunocompromised hosts with a focus on beta-lactam (penicillin) allergy and sulfa-antibiotic (antimicrobial sulfurs) allergy labels.


Assuntos
Hipersensibilidade a Drogas , Antibacterianos/efeitos adversos , Hipersensibilidade a Drogas/epidemiologia , Humanos , Hospedeiro Imunocomprometido , Penicilinas , beta-Lactamas/efeitos adversos
19.
Transpl Infect Dis ; 24(5): e13906, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36254521

RESUMO

BACKGROUND: The effects of reported beta-lactam allergies on clinical outcomes have been understudied in lung transplant recipients. We evaluated reported beta-lactam allergies on clinical outcomes in this population. METHODS: A single-center retrospective cohort analysis was performed. One hundred and nine lung transplant recipients were identified and screened for a diagnosis of pneumonia. This cohort was divided into those with a reported beta-lactam allergy and those without a beta-lactam allergy. Antibiotic use was compared between groups. We also compared several clinical metrics, including rates of readmission, mortality, Clostridium difficile infection (CDI), allograft dysfunction, and isolation of carbapenem or fluoroquinolone non-susceptible organisms after treatment. RESULTS: Of the 109 lung transplant recipients, 18 (16.5%) were identified as having a reported beta-lactam allergy. Patients with a beta-lactam allergy label (BLAL) were found to have decreased utilization of beta-lactams (p < .001) and a trend toward increased use of carbapenems (p = .062) and aztreonam (p = .080). BLAL patients were found to have higher rates of CDI (p = .049) but were not found to have increased readmissions, mortality, allograft dysfunction, or isolation of carbapenem or fluoroquinolone non-susceptible organisms. Patients without a BLAL were found to have higher rates of acute kidney injury (AKI) (p = .035). CONCLUSIONS: Lung transplant recipients with BLAL are more likely to develop CDI, possibly due to increased use of carbapenems. We also found that patients without beta-lactam allergy were more likely to develop AKI. A multicenter study with a larger sample size might clarify the individual contributions of mutually confounding clinical parameters.


Assuntos
Injúria Renal Aguda , Infecções por Clostridium , Hipersensibilidade a Drogas , Hipersensibilidade , Pneumonia , Injúria Renal Aguda/tratamento farmacológico , Antibacterianos/efeitos adversos , Aztreonam , Carbapenêmicos , Infecções por Clostridium/epidemiologia , Fluoroquinolonas , Humanos , Hipersensibilidade/tratamento farmacológico , Pulmão , Pneumonia/tratamento farmacológico , Estudos Retrospectivos , Transplantados , beta-Lactamas/efeitos adversos
20.
Int J Mycobacteriol ; 11(3): 309-317, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36260451

RESUMO

Background: The World Health Organization Global Tuberculosis Report 2021 defines tuberculosis as the second infectious disease that causes sickness and death after COVID 19 and ranks it as the 13th among the global causes of death. However, the prevalence of the patients developing a hypersensitivity reaction against antituberculosis treatment is yet unknown. This study aimed to investigate the prevalence of drug allergy against antituberculosis treatment and the management of such a problem. Methods: This is a case--control study. All patients hospitalized in the tuberculosis inpatient service between February 01, 2015 and May 01, 2021 due to hypersensitivity reaction or who developed hypersensitivity during hospitalization were included in the case group. Patients who received inpatient treatment between the same dates and did not develop any drug allergy were included in the control group. The demographic characteristics of the patients, the tuberculosis diagnostic indicator, the type of hypersensitivity reaction that developed, the duration of the manifestation of the reaction and its treatment were evaluated for the purpose of the study. Results: A total of 2677 patients were hospitalized in the tuberculosis inpatient service between the specified dates. Two hundred and ten patients were consulted for drug hypersensitivity reactions in the Allergy Clinic. The prevalence of drug allergy in inpatients was calculated as 7.8%. One hundred and forty-eight patients examined by the authors were included in the study. Seventy-nine of the 148 patients (53.4%) who developed a hypersensitivity reaction were male, the mean age of these patients was 47.20 ± 18.95 years, 89.2% (n = 132) were citizens of the Republic of Turkey, 7.4% (n = 11) of the patients had received tuberculosis treatment before, 16.9% (25) had developed antituberculosis drug resistance and the bacteriological diagnosis was present in 79.7% (118) of the patients. Chi-square test results applied in the allergy group revealed that the risk of developing a hypersensitivity reaction is statistically significantly higher in female patients (P < 0.001), Turkish citizen patients (P = 0.004), in new cases (P = 0.017), in the group not diagnosed bacteriologically (histopathologically, clinically, and radiologically) (P = 0.006). The results of the logistic regression analysis performed also revealed that the risk of developing a hypersensitivity reaction is statistically significantly higher in female patients (P = 0.006), Turkish citizen patients (P = 0.023), in new cases (P = 0.017) and in the group not diagnosed bacteriologically (histopathologically, clinically, and radiologically) (P = 0.006). The success of the treatment was higher in the group that developed a hypersensitivity reaction compared to the control group. About 63.5% (94) of the patients examined developed Type I hypersensitivity reactions, whereas 36.7% (53) of the patients examined developed Type IV hypersensitivity reactions. Type I and Type IV reactions were observed simultaneously in a single patient. Considering the prevalence of developing a hypersensitivity reaction, pyrazinamide was determined as the drug inducing the hypersensitivity reaction in 25 (48.1%) patients. This figure was 15 patients (28.2%) for rifampicin, nine patients (17.3%) for isoniazid, and five patients (9.6%) for ethambutol. As a result, even patients who developed Type I or Type IV reactions were able to complete their antituberculous drug regimens with successful desensitization. Conclusion: The risk of developing an allergic reaction in patients who are administered on antituberculosis treatment is common, particularly in the first 2 months of treatment. However, we believe that the compliance of the patients to the antituberculosis treatment has been improved at the end of appropriate management of hypersensitivity reactions and the treatment results in success.


Assuntos
COVID-19 , Hipersensibilidade a Drogas , Tuberculose , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Antituberculosos/efeitos adversos , Isoniazida/uso terapêutico , Etambutol/uso terapêutico , Pirazinamida/uso terapêutico , Rifampina/uso terapêutico , COVID-19/tratamento farmacológico , COVID-19/epidemiologia , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia , Hipersensibilidade a Drogas/epidemiologia , Hipersensibilidade a Drogas/etiologia , Hipersensibilidade a Drogas/tratamento farmacológico
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