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1.
Am J Case Rep ; 22: e933380, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34582431

RESUMO

BACKGROUND Patients taking azathioprine (AZA) are very susceptible to development of cytomegalovirus (CMV) infection. The symptoms of CMV infection are varied. In some rare cases, CMV infection can even result in nephrotic syndrome. CASE REPORT Here, we present a rare case of nephrotic syndrome associated with CMV infection, induced by azathioprine intake. The patient, diagnosed with myasthenia gravis, was initially treated with azathioprine for 2 years. Then, the patient was admitted to the hospital due to nephrotic syndrome and acute kidney injury. Minimal change disease with acute tubular necrosis were diagnosed through biopsy. After an initial good response to hemodialysis and steroids, the patient developed severe pneumonia and oral ulcers. Further anti-CMV IHC staining of kidney tissues showed positive cells in tubules, indicating nephrotic syndrome secondary to CMV infection. CONCLUSIONS This case reminded us that CMV may be an under-recognized cause of nephrotic syndrome. Patients treated with azathioprine are very susceptible to developing CMV infection. During the diagnosis of nephrotic syndrome, we should always take CMV infection into consideration, especially in patients with on azathioprine.


Assuntos
Infecções por Citomegalovirus , Miastenia Gravis , Síndrome Nefrótica , Azatioprina/efeitos adversos , Citomegalovirus , Infecções por Citomegalovirus/tratamento farmacológico , Humanos , Miastenia Gravis/complicações , Miastenia Gravis/tratamento farmacológico , Síndrome Nefrótica/complicações , Síndrome Nefrótica/tratamento farmacológico
2.
Scand J Gastroenterol ; 56(11): 1323-1327, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34399630

RESUMO

INTRODUCTION AND AIM: Thiopurines - although used frequently in inflammatory bowel diseases (IBD) - carry a significant safety risk, particularly with prolonged use and/or in elderly patients. Stopping therapy, however, may trigger relapses. We assessed the long-term outcome of elderly IBD patients after discontinuation of thiopurine while in clinical remission. METHODS: Electronic medical records from IBD patients >60 years whoever received thiopurine treatment were reviewed. Patients who stopped thiopurine after 60 years of age while in clinical and/or endoscopic remission were included. Long-term outcomes included duration of clinical remission, time to clinical relapse, and development of malignancy. RESULTS: In total, 142 patients receiving thiopurines while they were >60 years were identified. Ninety-one patients stopped thiopurines at >60years while in clinical and/or endoscopic remission. After a median follow-up of 66 months, 28 (30.8%) developed a clinical relapse. The median duration of TP therapy in relapses was significantly shorter than in patients who remained in remission (median 45 vs. 103 months, respectively; p = .005). After relapse, 10 patients started a biological (36%) and seven received steroids (25%). Surgery was needed in 36% of patients (10/28). Overall, 26 malignancies developed. CONCLUSION: Discontinuation of TP in elderly IBD patients in clinical and/or endoscopic remission results in sustained clinical remission in two-thirds of patients. Patients who flare can mostly be rescued with biologicals although one-third necessitate surgery. A significant proportion of patients developed malignancies under but also after thiopurines discontinuation, indicating that these patients necessitate a continued close follow-up. Decision-making in this vulnerable subgroup of patients remains difficult.


Assuntos
Azatioprina , Doenças Inflamatórias Intestinais , Idoso , Azatioprina/efeitos adversos , Humanos , Imunossupressores/efeitos adversos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Mercaptopurina/efeitos adversos , Recidiva , Estudos Retrospectivos , Esteroides , Resultado do Tratamento
3.
Medicine (Baltimore) ; 100(34): e26956, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34449460

RESUMO

ABSTRACT: Azathioprine (AZA), methotrexate, or rituximab is used for the maintenance therapy of antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Although the efficacy of tacrolimus (TAC) in various autoimmune diseases has been demonstrated, there have been few reports on the efficacy of TAC in AAV. We investigated the efficacy of TAC as maintenance therapy for AAV and compared its efficacy with that of AZA.We retrospectively analyzed the medical records of 81 patients with AAV who received cyclophosphamide as induction therapy and AZA or TAC as maintenance therapy. All-cause death, relapse, and progression to end-stage renal disease (ESRD) were analyzed.Among 81 patients with AAV, 69 patients received AZA alone, 6 patients received TAC alone, and 6 patients received TAC after AZA for maintenance therapy. Overall, 11 patients (13.6%) died, 30 patients (37.0%) experienced relapse, and 16 patients (19.8%) progressed to ESRD during a median of 33.8 months. No significant differences were observed in cumulative patients', relapse-free, and ESRD-free survival rates between patients administered AZA alone and TAC alone. There were no significant differences in the cumulative patients' and relapse-free survival rate between patients who received AZA alone and TAC after AZA. However, the cumulative ESRD-free survival rate was lower in patients who received TAC after AZA than in those who received AZA alone (P = .027).Patients who received TAC as maintenance therapy showed a higher incidence of ESRD than those who received AZA; however, this might be attributed to the lack of efficacy of AZA rather than the low ESRD prevention effect of TAC.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Azatioprina/uso terapêutico , Imunossupressores/uso terapêutico , Tacrolimo/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/patologia , Azatioprina/efeitos adversos , Ciclofosfamida/uso terapêutico , Progressão da Doença , Feminino , Humanos , Imunossupressores/efeitos adversos , Incidência , Falência Renal Crônica/patologia , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Taxa de Sobrevida , Tacrolimo/efeitos adversos
4.
Trials ; 22(1): 530, 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34380536

RESUMO

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease that can involve multiple organs or systems. Lupus nephritis (LN) is associated with high mortality and morbidity. However, plenty of patients do not respond to present treatment or relapse. Iguratimod (IGU) is a new small molecular, anti-rheumatic drug and has shown the potential for drug repurposing from rheumatoid arthritis (RA) to LN treatment. It has been approved for treating RA in northeast Asia. Beyond expectation in a recent observational study, over 90% of thirteen refractory LN patients responded to iguratimod monotherapy in 24 weeks, with no steroids dose increasing or any other medication add-on during the entire follow-up. METHODS/DESIGN: This study is a multi-center, randomized, 52-week parallel positive drug-controlled study. The study was designed as a head-to-head comparison between the iguratimod and present first-line therapy on LN patients. A total of 120 patients (60 patients each group) is in the enrolling plan. All enrolled patients are assigned randomly into trial and control groups. The patients will be selected from six study sites in China and will all have biopsy-proven active lupus nephritis. In the first 24 weeks of the trial, IGU is compared with cyclophosphamide as an induction therapy, and in the second 24 weeks, IGU is compared with azathioprine as a maintenance therapy. The primary outcome is renal remission rate including both complete remission and partial remission at week 52, which will be analyzed using a non-inferiority hypothesis test. DISCUSSION: Most patients diagnosed with SLE will develop LN within 5 years and LN remains a major cause of morbidity and death for SLE patients. Although some medications are proven effective for the treatment of this condition, at least 20-35% LN patients have to suffer from relapse or ineffective treatment and medication intolerance is also frequent. This trial is designed to demonstrate whether iguratimod can be used as an alternative induction or maintenance therapy in subjects who have lupus nephritis. Data from this study will provide an evidence on whether or not iguratimod should be recommended to active LN patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT02936375 . Registered on October 18, 2016.


Assuntos
Azatioprina , Nefrite Lúpica , Azatioprina/efeitos adversos , Cromonas , Ciclofosfamida/efeitos adversos , Humanos , Imunossupressores/efeitos adversos , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/tratamento farmacológico , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão , Sulfonamidas , Resultado do Tratamento
5.
Transplant Proc ; 53(6): 1951-1956, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34274119

RESUMO

BACKGROUND: Diarrhea is a common adverse effect of mycophenolate treatment in renal transplant recipients. In patients with mycophenolate-induced diarrhea, one option is to switch to mycophenolate to azathioprine. In this study, we aimed to define the safety and efficacy of switching from mycophenolate to azathioprine for mycophenolate-related diarrhea in renal transplant recipients. METHODS: A total of 177 patients, 59 of whom were switched to azathioprine because of diarrhea and 118 of whom comprised a matched control group without diarrhea and continued mycophenolate treatment participated in this study. We analyzed the effect of switching to azathioprine from mycophenolate on amelioration of diarrhea and graft survival. RESULTS: We observed that 89.8% of patients who switched to azathioprine because of diarrhea had improved diarrhea complaints. Patients switched to azathioprine because of diarrhea had lower glomerular filtration rates (P < .001) and higher proteinuria (P < .001) compared with the control group before the switch. Patients switched to azathioprine compared with a subgroup of 59 control patients were matched to patients switched to azathioprine in terms of baseline renal function and proteinuria in addition to demographic parameters had higher 10-year graft loss compared with patients who continued mycophenolate (P = .03). Particularly in patients with a glomerular filtration rate <30 mL/min at the time of conversion, the risk of early graft loss was high. CONCLUSIONS: Although switching from mycophenolate to azathioprine was an effective approach to improve diarrhea, this approach is associated with increased risk of graft loss.


Assuntos
Diarreia , Transplante de Rim , Azatioprina/efeitos adversos , Diarreia/induzido quimicamente , Rejeição de Enxerto , Humanos , Imunossupressores/efeitos adversos , Rim/fisiologia , Transplante de Rim/efeitos adversos , Ácido Micofenólico/efeitos adversos
6.
PLoS Med ; 18(6): e1003668, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34166370

RESUMO

BACKGROUND: We compared protection of mycophenolate mofetil (MMF) and azathioprine (AZA) against acute cellular rejection (ACR) and chronic allograft nephropathy (CAN) in kidney transplant recipients on steroid-free, low-dose cyclosporine (CsA) microemulsion maintenance immunosuppression. METHODS AND FINDINGS: ATHENA, a pragmatic, prospective, multicenter trial conducted by 6 Italian transplant centers, compared the outcomes of 233 consenting recipients of a first deceased donor kidney transplant induced with low-dose thymoglobulin and basiliximab and randomized to MMF (750 mg twice/day, n = 119) or AZA (75 to 125 mg/day, n = 114) added-on maintenance low-dose CsA microemulsion and 1-week steroid. In patients without acute clinical or subclinical rejections, CsA dose was progressively halved. Primary endpoint was biopsy-proven CAN. Analysis was by intention to treat. Participants were included between June 2007 and July 2012 and followed up to August 2016. Between-group donor and recipient characteristics, donor/recipient mismatches, and follow-up CsA blood levels were similar. During a median (interquartile range (IQR)) follow-up of 47.7 (44.2 to 48.9) months, 29 of 87 biopsied patients on MMF (33.3%) versus 31 of 88 on AZA (35.2%) developed CAN (hazard ratio (HR) [95% confidence interval (CI)]: 1.147 (0.691 to 1.904, p = 0.595). Twenty and 21 patients on MMF versus 34 and 14 on AZA had clinical [HR (95% CI): 0.58 (0.34 to 1.02); p = 0.057) or biopsy-proven subclinical [HR (95% CI): 1.49 (0.76 to 2.92); p = 0.249] ACR, respectively. Combined events [HR (95% CI): 0.85 (0.56 to 1.29); p = 0.438], patient and graft survival, delayed graft function (DGF), 3-year glomerular filtration rate (GFR) [53.8 (40.6;65.7) versus 49.8 (36.8;62.5) mL/min/1.73 m2, p = 0.50], and adverse events (AEs) were not significantly different between groups. Chronicity scores other than CAN predict long-term graft outcome. Study limitations include small sample size and unblinded design. CONCLUSIONS: In this study, we found that in deceased donor kidney transplant recipients on low-dose CsA and no steroids, MMF had no significant benefits over AZA. This finding suggests that AZA, due to its lower costs, could safely replace MMF in combination with minimized immunosuppression. TRIAL REGISTRATION: ClinicalTrials.gov NCT00494741; EUDRACT 2006-005604-14.


Assuntos
Azatioprina/administração & dosagem , Ciclosporina/administração & dosagem , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Imunossupressores/administração & dosagem , Transplante de Rim , Ácido Micofenólico/administração & dosagem , Adulto , Idoso , Azatioprina/efeitos adversos , Ciclosporina/efeitos adversos , Quimioterapia Combinada , Feminino , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/imunologia , Humanos , Imunossupressores/efeitos adversos , Itália , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/efeitos adversos , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento
7.
Medicine (Baltimore) ; 100(25): e26440, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160436

RESUMO

RATIONALE: Relapsed or refractory acute lymphoblastic leukemia poses a significant clinical challenge due to its poor prognosis, showing survival rates of less than a year even with the use of novel therapies. In this report, we describe the safe and effective use of trametinib combined with dasatinib in a patient with acute lymphoblastic leukemia (ALL). To the best of our knowledge, this is the first report on the successful use of 2 targeted drugs such as trametinib and dasatinib in a pediatric patient with Ph+ ALL and recurrent pancreatitis. PATIENT CONCERNS: A 6-year-old boy with ALL and Philadelphia chromosome (Ph+) who had recurrent asparaginase-associated pancreatitis. DIAGNOSIS: The patient was diagnosed with ALL, based on clinical features, laboratory analyses, bone marrow aspiration evaluation in morphology, immunology, cytogenetics, and molecular. INTERVENTIONS: The patient was treated with dasatinib combined with an intermediate risk-oriented chemotherapy. However, owing to recurrent asparaginase-associated pancreatitis, the patient has to abandon asparaginase in consolidation. Considering the high risk of relapse, we used trametinib and dasatinib combined with chemotherapy as maintenance chemotherapy. OUTCOMES: After 6 months, there were no obvious side effects or residual disease. LESSONS: We suggest that the combination of trametinib and dasatinib may represent a viable option to treat patients with potential relapsed/refractory Ph+ ALL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Dasatinibe/administração & dosagem , Pancreatite/induzido quimicamente , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Piridonas/administração & dosagem , Pirimidinonas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Asparaginase/administração & dosagem , Asparaginase/efeitos adversos , Azatioprina/administração & dosagem , Azatioprina/efeitos adversos , Criança , Quimioterapia de Consolidação/métodos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Dasatinibe/efeitos adversos , Humanos , Quimioterapia de Manutenção/métodos , Masculino , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Piridonas/efeitos adversos , Pirimidinonas/efeitos adversos , Resultado do Tratamento
8.
Brasília; CONITEC; jun. 2021.
Não convencional em Português | BRISA/RedTESA | ID: biblio-1293255

RESUMO

INTRODUÇÃO: A retocolite ulcerativa (RCU), ou colite ulcerativa, é uma doença caracterizada pela ocorrência de episódios de inflamação restrita à mucosa do cólon, podendo envolver o reto e se estender por outras partes proximais do cólon. Os pacientes apresentam diarreia, podendo ser associada com a presença de sangue. Os sintomas incluem dor abdominal, urgência, incontinência e tenesmo, que apresentam de forma gradual e progressiva, podendo estender-se por várias semanas. Febre, fadiga, perda de peso, dispneia, palpitação, anemia e deficiência de ferro podem ocorrer. A RCU pode ser dividida em fase ativa e estádio de remissão. A fase ativa é caracterizada pela presença de sintomas e lesões ativas da mucosa e a remissão é caracterizada pela resolução dos sintomas e desaparecimento de achados na mucosa. A doença ocorre gradualmente, seguida de períodos de remissão espontânea e recaídas subsequentes. A incidência da doença é semelhante entre homens e mulheres, sendo que a idade de início é entre 30 e 40 anos. O tratamento da RCU consiste em aminossalicilatos orais e por via retal, corticoides, imunossupressores e medicamentos biológicos, e é feito d


Assuntos
Humanos , Proctocolite/tratamento farmacológico , Azatioprina/efeitos adversos , Corticosteroides/efeitos adversos , Janus Quinases/antagonistas & inibidores , Mercaptopurina/efeitos adversos , Sistema Único de Saúde , Brasil , Análise Custo-Benefício
9.
J Clin Neurosci ; 88: 70-74, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33992207

RESUMO

Treatments of myasthenia gravis (MG) usually include immunosuppressants such as glucocorticoids, tacrolimus, and azathioprine (AZA). In clinical practice, azathioprine therapy is thought to have a potential risk for developing secondary malignancies in myasthenia gravis patients. However, published data on the long-term safety of azathioprine in myasthenia gravis patients are limited and not consistent among studies. To explore cancer occurrence following azathioprine therapy in myasthenia gravis patients in the long term, we searched Medline, EMBASE, and the Cochrane Library for terms related to azathioprine, myasthenia gravis and cancer occurrence. Two investigators independently extracted trial data. A pooled estimate was calculated from fixed-effects meta-analysis. Our analysis included 1650 azathioprine-treated patients and 2481 non-azathioprine-treated patients. All five studies showed some concerns regarding the risk of bias. In a meta-analysis of 5 studies, we observed no significantly elevated risk of cancer occurrence among individuals with prior myasthenia gravis diagnosis who received long-term azathioprine treatment (OR 1.09; 95% CI 0.86-1.38, p = 0.46). Prospective studies are needed to observe the safety of azathioprine.


Assuntos
Azatioprina/efeitos adversos , Imunossupressores/efeitos adversos , Miastenia Gravis/tratamento farmacológico , Neoplasias/induzido quimicamente , Neoplasias/epidemiologia , Humanos , Estudos Prospectivos
10.
Am J Gastroenterol ; 116(4): 671-672, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33982934

RESUMO

This editorial comments on the study by Khan et al. that describes potential risk of acute myeloid leukemia or myeloproliferative disorder among thiopurine therapy.


Assuntos
Doenças Inflamatórias Intestinais , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Azatioprina/efeitos adversos , Humanos , Incidência , Leucemia Mieloide Aguda/tratamento farmacológico
11.
BMJ Case Rep ; 14(5)2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-34011657

RESUMO

Azathioprine hypersensitivity syndrome is a rare but potentially severe side effect of azathioprine use. It has a variable and non-specific presentation making it difficult to distinguish from sepsis or disease relapse. High clinical suspicion is therefore required for recognition and prompt cessation of azathioprine for symptom resolution. Herewith two cases of severe azathioprine hypersensitivity syndrome are described, one in association with Sweet syndrome. Both presented with vague symptoms 2 weeks after commencing azathioprine for antineutrophil cytoplasmic antibody vasculitis. The differentials of sepsis and disease relapse were considered prior to cessation of azathioprine which resulted in a dramatic improvement in both cases. These cases highlight the diagnostic challenge azathioprine hypersensitivity syndrome presents. It should be suspected when there is a temporal relationship to drug initiation, with absence of infection or serological evidence of disease relapse.


Assuntos
Síndrome de Hipersensibilidade a Medicamentos , Hipersensibilidade a Drogas , Síndrome de Sweet , Anticorpos Anticitoplasma de Neutrófilos , Azatioprina/efeitos adversos , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/etiologia , Humanos , Imunossupressores/efeitos adversos , Síndrome de Sweet/induzido quimicamente , Síndrome de Sweet/diagnóstico , Síndrome de Sweet/tratamento farmacológico
12.
Medicine (Baltimore) ; 100(18): e25781, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33950972

RESUMO

INTRODUCTION: Azathioprine (AZA) has been widely used for the treatment of various immune-related diseases and has become a mainstay in the treatment of inflammatory bowel disease. However, patients with genetic mutations may experience severe adverse events when treated with azathioprine. Most of the previous literature focused on the TPMP gene-related adverse reactions, herein, we report a case of Crohn's disease patient with nucleoside diphosphate-linked moiety X motif 15 gene (NUDT15) variation and wild-type TPMP gene who developed toxoplasma gondii infection after azathioprine treatment. PATIENT CONCERNS: A 56-year-old Crohn's disease patient developed toxoplasma gondii infection within 2 months after the administration of azathioprine; however, he had no relevant high-risk factors. DIAGNOSIS: Subsequent genetic testing revealed that the patient was heterozygous for NUDT15. Therefore, it was reasonable to consider that the patient's genetic mutation resulted in reduced tolerance to azathioprine, leading to low immunity and eventually toxoplasma infection. INTERVENTIONS: AZA was then discontinued; after anti-infection, antipyretic and other supportive treatments were administered, the patient's condition gradually improved. OUTCOMES: The patient was followed up at 1, 3, and 6 months after discharge; fortunately, he was in good health. CONCLUSION: We report a case of Crohn's disease in a patient who developed severe pneumonia caused by toxoplasma gondii infection due to the administration of AZA, with normal TPMP gene but NUDT15 gene mutation. This indicates that NUDT15 variation may contribute to severe adverse events in patients treated with azathioprine, and we suggest that NUDT15 genotype be detected before the use of azathioprine in order to provide personalized therapy and reduce side effects.


Assuntos
Azatioprina/efeitos adversos , Doença de Crohn/tratamento farmacológico , Pneumonia/diagnóstico , Pirofosfatases/genética , Toxoplasma/imunologia , Toxoplasmose/diagnóstico , Azatioprina/farmacocinética , Doença de Crohn/genética , Doença de Crohn/imunologia , Análise Mutacional de DNA , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Testes Farmacogenômicos , Pneumonia/genética , Pneumonia/imunologia , Pneumonia/parasitologia , Polimorfismo de Nucleotídeo Único , Pirofosfatases/metabolismo , Toxoplasma/isolamento & purificação , Toxoplasmose/genética , Toxoplasmose/imunologia , Toxoplasmose/parasitologia
13.
Clin Transl Gastroenterol ; 12(4): e00332, 2021 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-33821842

RESUMO

INTRODUCTION: Azathioprine-induced pancreatitis is an idiosyncratic and unpredictable response, occurring in up to 7% of azathioprine-exposed patients with inflammatory bowel disease (IBD). The haplotype HLADQA1-HLADRB1*07:01A>C is strongly associated with azathioprine-induced pancreatitis in IBD. We aimed to evaluate whether pretreatment HLADQA1-HLADRB1*07:01A>C screening will reduce the risk of azathioprine-induced pancreatitis. METHODS: Participants with IBD were screened for HLADQA1-HLADRB1*07:01A>C, and participants with a variant genotype were excluded from azathioprine treatment. Wild-type participants were started on azathioprine and followed for 3 months. The incidence of pancreatitis was compared with unscreened historical controls. RESULTS: HLADQA1-HLADRB1*07:01A>C screening resulted in an 11-fold reduction in the incidence of azathioprine-induced pancreatitis (n = 1/328 or 0.30% vs n = 13/373 or 3.4%). In propensity score-matched cohorts (age and sex), HLA DQA1-HLADRB1*07:01A>C screening was significantly associated with a reduction in the incidence of AZA-induced pancreatitis independent of weight, glucocorticoid exposure, and smoking status (adjusted odds ratio = 0.075, 95% confidence interval = 0.01-0.58, P = 0.01). Up to 45% (n = 271/599) of participants were excluded from azathioprine therapy based on the haplotype in the HLADQA1-HLADRB1*07:01A>C-screened cohort. DISCUSSION: HLADQA1-HLADRB1*07:01A>C screening reduced the risk of azathioprine-induced pancreatitis; however, using this strategy to guide the use of azathioprine therapy in IBD may eliminate a large proportion of patients from being eligible for treatment with azathioprine. In regions where there is access to other IBD therapies, and given the short-term and long-term toxicities associated with azathioprine, HLADQA1-HLADRB1*07:01A>C-screening may be a clinically relevant strategy for enhancing the safe use of azathioprine in IBD. In addition, cost-effectiveness analyses are needed to further solidify the utility of HLADQA1-HLADRB1*07:01A>C screening in IBD populations.


Assuntos
Azatioprina/efeitos adversos , Cadeias alfa de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Imunossupressores/efeitos adversos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/genética , Pancreatite/prevenção & controle , Polimorfismo Genético , Haplótipos , Humanos , Pancreatite/induzido quimicamente , Pontuação de Propensão , Estudos Prospectivos
15.
Int J Clin Pharmacol Ther ; 59(7): 535-538, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33860754

RESUMO

Azathioprine is one of the main drugs in the treatment of inflammatory bowel disease (IBD). It has been widely used in the remission and maintenance treatment of IBD. Some patients may experience some degree of myelosuppression, but very few patients experience severe myelosuppression. Here, we report a 20-year-old male Asian patient with severe myelosuppression due to azathioprine treatment of IBD. In this case, the azathioprine-related genotyping test showed that homozygous wild-type TPMT*3 but a c.415C>T homozygous mutation was found in NUDT15. Our report strengthens the association between genetic polymorphisms of azathioprine-metabolizing enzymes and severe myelosuppression. Therefore, we recommend routine NUDT15 c.415C>T phenotype testing prior to long-term azathioprine treatment to avoid severe myelosuppression.


Assuntos
Azatioprina , Doenças Inflamatórias Intestinais , Adulto , Azatioprina/efeitos adversos , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/genética , Masculino , Metiltransferases/genética , Fenótipo , Pirofosfatases/genética , Adulto Jovem
16.
BMJ Case Rep ; 14(4)2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33893128

RESUMO

This case report discusses the rare presentation of cytomegalovirus (CMV) pneumonitis in a young patient with moderately severe Crohn's disease managed with low dose azathioprine. CMV pneumonitis was initially suspected on CT chest images and confirmed by PCR for CMV. She was treated with intravenous ganciclovir and later stepped down to oral valganciclovir. Although this patient had a prolonged and complicated hospital admission, a good clinical outcome was achieved. CMV infection was raised as an early differential and antiviral treatment was started without delay. This case study, therefore, makes the case for increased awareness of the possibility of, and recognition of CMV pneumonitis among healthcare professionals as a way of preventing significant morbidity and mortality. It also raises awareness of checking for slow metabolisers of azathioprine before initiation to look for individuals who may be at increased risk of azathioprine's adverse effects.


Assuntos
Doença de Crohn , Infecções por Citomegalovirus , Pneumonia , Antivirais/efeitos adversos , Azatioprina/efeitos adversos , Doença de Crohn/tratamento farmacológico , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/tratamento farmacológico , Feminino , Ganciclovir/uso terapêutico , Humanos , Pneumonia/induzido quimicamente , Pneumonia/tratamento farmacológico
18.
BMC Pulm Med ; 21(1): 76, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33663455

RESUMO

BACKGROUND: Cryptococcus is one of the major fungal pathogens infecting the lungs. Pulmonary cryptococcal infection is generally considered a community-acquired condition caused by inhalation of dust contaminated with fungal cells from the environment. Here, we report a case developing pulmonary cryptococcosis 3 months after hospital admission, which has rarely been reported before. CASE PRESENTATION: A 73-year-old female patient who was previously immunocompetent experienced persistent dry cough for 2 weeks, 3 months after admission. Chest computed tomography (CT) showed a new solitary pulmonary nodule developed in the upper lobe of the left lung. Staining and culture of expectorated sputum smears were negative for bacteria, acid-fast bacilli, or fungus. The patient then underwent biopsy of the lesion. Histopathology findings and a positive serum cryptococcal antigen titer (1:8) indicated pulmonary cryptococcosis. Daily intravenous 400 mg fluconazole was administered initially followed by oral fluconazole therapy. Follow-up chest CT after 3 months of antifungal therapy showed complete disappearance of the pulmonary nodule. Respiratory symptoms of the patient also resolved. A complete investigation excluded the possibility of a patient-to-patient transmission or primarily acquiring the infection from the hospital environment. Based on the patient's history of exposure to pigeons before admission and recent steroid and azathioprine use after admission for the treatment of myasthenic crisis, reactivation of a latent pulmonary cryptococcal infection acquired before admission, in this case, is impressed. CONCLUSIONS: Although rarely reported, pulmonary cryptococcal infection should be included in the differential diagnosis of hospitalized patients with respiratory symptoms, especially in those with predisposing risk factors. Chest image studies and further surgical biopsy are needed for confirmation.


Assuntos
Azatioprina/efeitos adversos , Criptococose/diagnóstico , Pneumopatias Fúngicas/diagnóstico , Pulmão/patologia , Esteroides/efeitos adversos , Idoso , Antígenos de Fungos/sangue , Biópsia , Criptococose/etiologia , Criptococose/patologia , Diagnóstico Tardio , Diagnóstico Diferencial , Feminino , Humanos , Imunocompetência , Pneumopatias Fúngicas/etiologia , Pneumopatias Fúngicas/patologia , Tomografia Computadorizada por Raios X
19.
Arq Neuropsiquiatr ; 79(3): 229-232, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33729325

RESUMO

BACKGROUND: Azathioprine is a common first-line therapy for neuromyelitis optica spectrum disorder (NMOSD). OBJECTIVE: The aim of this study was to determine whether long-term treatment (>10 years) with azathioprine is safe in NMOSD. Methods: We conducted a retrospective medical record review of all patients at the School of Medicine of the University of São Paulo (São Paulo, Brazil) who fulfilled the 2015 international consensus diagnostic criteria for NMOSD and were treated with azathioprine for at least 10 years. RESULTS: Out of 375 patients assessed for eligibility, 19 were included in this analysis. These patients' median age was 44 years (range=28-61); they were mostly female (17/19) and AQP4-IgG seropositive (18/19). The median disease duration was 15 years (range=10-39) and most patients presented a relapsing clinical course (84.2%). The median duration of treatment was 11.9 years (range=10.0-23.8). The median annualized relapse rates (ARR) pre- and post-treatment with azathioprine were 1 (range=0.1-2) and 0.1 (range=0-0.35); p=0.09. Three patients (15.7%) had records of adverse events during the follow-up, which consisted of chronic B12 vitamin deficiency, pulmonary tuberculosis and breast cancer. CONCLUSION: Azathioprine may be considered a safe agent for long-term treatment (>10 years) of NMOSD, but continuous vigilance for infections and malignancies is required.


Assuntos
Neuromielite Óptica , Adulto , Aquaporina 4 , Azatioprina/efeitos adversos , Brasil , Feminino , Humanos , Masculino , Neuromielite Óptica/tratamento farmacológico , Recidiva , Estudos Retrospectivos
20.
Expert Rev Clin Pharmacol ; 14(4): 491-501, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33682590

RESUMO

Background: Prevalence and impact of thiopurine S-methyltransferase (TPMT) and Nudix hydrolase (NUDT15) minor allele frequencies in South Asian population is unclear.Methods: We searched PubMed and Embase with keywords-TPMT and NUDT15 combined with South Asian countries. We included studies reporting frequency of TPMT and NUDT15 polymorphisms. We estimated the pooled prevalence of TPMT and NUDT15 polymorphisms and their impact on pooled odds ratio of adverse events with thiopurines.Results: We included 26 studies in our analysis. The pooled prevalence of NUDT15 and TPMT polymorphisms was 16.5% (95% CI: 13.09-20.58) and 4.57% (95% CI: 3.66-5.68), respectively. In patients with adverse effects, the pooled prevalence of NUDT15 and TPMT polymorphism was 49.51% (95% C.I. 21.69-77.64) and 9.47% (95% C.I. 5.39-16.11), respectively. The odds ratio (OR) of adverse events with presence of TPMT polymorphisms was 3.65 (95% C.I., 1.43-9.28). The pooled OR for adverse events in presence of NUDT15 polymorphism was 12.63 (95% C.I., 3.68-43.26).Conclusion: NUDT15 were reported more frequently than the TPMT polymorphisms in South Asian population and were more frequently associated with adverse events. These findings may have implications for preemptive testing amongst South Asian population and immigrants prior to starting thiopurines.


Assuntos
Metiltransferases/genética , Pirofosfatases/genética , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Azatioprina/administração & dosagem , Azatioprina/efeitos adversos , Azatioprina/metabolismo , Humanos , Imunossupressores/metabolismo , Mercaptopurina/administração & dosagem , Mercaptopurina/efeitos adversos , Mercaptopurina/metabolismo , Metiltransferases/metabolismo , Polimorfismo Genético , Pirofosfatases/metabolismo
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