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1.
Eur J Gen Pract ; 27(1): 313-319, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34743668

RESUMO

BACKGROUND: Coeliac disease (CD) is a highly prevalent (∼1%) disease that allegedly remains undiagnosed in over 80% of the cases because of atypical symptoms or silent disease. Currently, it is unknown how GPs deal with (suspected) CD. OBJECTIVES: This study aimed to better understand the diagnostic approach and the clinical reasoning process of GPs concerning CD and concurrently address diagnostic pitfalls. METHODS: A questionnaire with case vignettes to assess the knowledge, diagnostic reasoning pattern and practice for CD by GPs was developed. It was sent through academic GP research networks (encompassing over 1500 GPs) in two large cities and to smaller practices in rural areas. The questionnaire was composed of seven background questions, 13 questions related to four case vignettes and six additional CD-related questions. RESULTS: Responses were received from 106 GPs. Knowledge on risk factors for CD and appropriate testing of at-risk populations was limited. Twenty-two percent would diagnose CD in adults exclusively based on serology, without histopathological confirmation. In total, 99% would refer a newly diagnosed patient to a dietitian to initiate a gluten-free diet (GFD). In the absence of symptoms, only 33% would initiate a GFD. CONCLUSION: The results of this study have given us insight into the diagnostic process of GPs encountering patient with gluten-related complaints. Multiple serology test is available and used, while a positive serology test is not always followed up by a gastroduodenal biopsy to confirm the diagnosis. Most GPs would refer a symptomatic CD patient to a dietician for a GFD.


Assuntos
Doença Celíaca , Medicina Geral , Clínicos Gerais , Adulto , Doença Celíaca/diagnóstico , Doença Celíaca/terapia , Dieta Livre de Glúten , Humanos , Inquéritos e Questionários
2.
Dig Dis Sci ; 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34729677

RESUMO

BACKGROUND: Beneficial response to first-line immunosuppressive azathioprine in patients with inflammatory bowel disease (IBD) is low due to high rates of adverse events. Co-administrating allopurinol has been shown to improve tolerability. However, data on this co-therapy as first-line treatment are scarce. AIM: Retrospective comparison of long-term effectiveness and safety of first-line low-dose azathioprine-allopurinol co-therapy (LDAA) with first-line azathioprine monotherapy (AZAm) in patients with IBD without metabolite monitoring. METHODS: Clinical benefit was defined as ongoing therapy without initiation of steroids, biologics or surgery. Secondary outcomes included CRP, HBI/SCCAI, steroid withdrawal and adverse events. RESULTS: In total, 166 LDAA and 118 AZAm patients (median follow-up 25 and 27 months) were evaluated. Clinical benefit was more frequently observed in LDAA patients at 6 months (74% vs. 53%, p = 0.0003), 12 months (54% vs. 37%, p = 0.01) and in the long-term (median 36 months; 37% vs. 24%, p = 0.04). Throughout follow-up, AZAm patients were 60% more likely to fail therapy, due to a higher intolerance rate (45% vs. 26%, p = 0.001). Only 73% of the effective AZA dose was tolerated in AZAm patients, while LDAA could be initiated and maintained at its target dose. Incidence of myelotoxicity and elevated liver enzymes was similar in both cohorts, and both conditions led to LDAA withdrawal in only 2%. Increasing allopurinol from 100 to 200-300 mg/day significantly lowered liver enzymes in 5/6 LDAA patients with hepatotoxicity. CONCLUSIONS: Our poor AZAm outcomes emphasize that optimization of azathioprine is needed. We demonstrated a long-term safe and more effective profile of first-line LDAA. This co-therapy may therefore be considered standard first-line immunosuppressive.

4.
J Clin Gastroenterol ; 55(10): 823-829, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34617932

RESUMO

Climate change has been described as the greatest public health threat of the 21st century. It has significant implications for digestive health. A multinational team with representation from all continents, excluding Antarctica and covering 18 countries, has formulated a commentary which outlines both the implications for digestive health and ways in which this challenge can be faced.


Assuntos
Mudança Climática , Gastroenterologia , Humanos
6.
Ther Drug Monit ; 43(5): 617-623, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34521801

RESUMO

BACKGROUND: In inflammatory bowel disease (IBD), conventional thiopurine users cease treatment in 60% of cases within 5 years, mostly because of adverse events or nonresponse. In this study, the authors aimed to investigate the role of 6-thioguanine nucleotide (TGN) measurements, geno/phenotyping of thiopurine S-methyltransferase (TPMT), and their mutual relationship with TG therapy in IBD. METHODS: An international retrospective, multicenter cohort study was performed at 4 centers in the Netherlands (Máxima Medical Centre) and the United Kingdom (Guy's and St. Thomas' Hospital, Queen Elizabeth Hospital, and East Surrey Hospital). RESULTS: Overall, 526 6-TGN measurements were performed in 316 patients with IBD. The median daily dosage of TG was 20 mg/d (range 10-40 mg/d), and the median duration of TG use was 21.1 months (SD, 28.0). In total, 129 patients (40.8%) had a known TPMT status. In the variant-type and wild-type TPMT genotype metabolism groups, median 6-TGN values were 1126 [interquartile range (IQR) 948-1562] and 467.5 pmol/8 × 10E8 red blood cells (RBCs) (IQR 334-593). A significant difference was observed between the 2 groups (P = 0.0001, t test). For TPMT phenotypes, in the slow, fast, and normal metabolism groups, the median 6-TGN values were 772.0 (IQR 459-1724), 296.0 (IQR 200-705), and 774.5 pmol/8 × 10E8 RBCs (IQR 500.5-981.5), with a significant difference observed between groups (P < 0.001, analysis of variance). CONCLUSIONS: Our findings indicated that TPMT measurements at TG initiation can be useful but are not necessary for daily practice. TPMT genotypes and phenotypes are both associated with significant differences in 6-TGN levels between metabolic groups. However, the advantage of TG remains that RBC 6-TGN measurements are not crucial to monitor treatments in patients with IBD because these measurements did not correlate with laboratory result abnormalities. This presents as a major advantage in countries where patients cannot access these diagnostic tests.


Assuntos
Imunossupressores , Doenças Inflamatórias Intestinais , Metiltransferases , Tioguanina , Adulto , Azatioprina , Feminino , Genótipo , Nucleotídeos de Guanina , Humanos , Imunossupressores/farmacocinética , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/genética , Masculino , Mercaptopurina , Metiltransferases/genética , Pessoa de Meia-Idade , Fenótipo , Estudos Retrospectivos , Tioguanina/farmacocinética , Tionucleotídeos
7.
Eur J Drug Metab Pharmacokinet ; 46(6): 743-758, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34487330

RESUMO

Thiopurines (mercaptopurine, azathioprine and thioguanine) are well-established maintenance treatments for a wide range of diseases such as leukemia, inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE) and other inflammatory and autoimmune diseases in general. Worldwide, millions of patients are treated with thiopurines. The use of thiopurines has been limited because of off-target effects such as myelotoxicity and hepatotoxicity. Therefore, seeking methods to enhance target-based thiopurine-based treatment is relevant, combined with pharmacogenetic testing. Controlled-release formulations for thiopurines have been clinically tested and have shown promising outcomes in inflammatory bowel disease. Latest developments in nano-formulations for thiopurines have shown encouraging pre-clinical results, but further research and development are needed. This review provides an overview of novel drug delivery strategies for thiopurines, reviewing modified release formulations and with a focus on nano-based formulations.

8.
Clin Transl Gastroenterol ; 12(8): e00387, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34333499

RESUMO

INTRODUCTION: Adult-onset autoimmune enteropathy (AIE) is a rare cause of severe chronic diarrhea because of small intestinal villous atrophy. We report on patients with adult-onset AIE in an European referral center. METHODS: Retrospective study including patients diagnosed with AIE in the Amsterdam UMC, location VUmc, between January 2003 and December 2019. Clinical, serological, and histological features and response to treatment were reported. The specificity of antienterocyte antibodies (AEA) was evaluated by examining the prevalence of AEA in (i) controls (n = 30) and in patients with (ii) AIE (n = 13), (iii) celiac disease (CD, n = 52), (iv) refractory celiac disease type 2 (n = 18), and (v) enteropathy-associated T-cell lymphoma (EATL, n = 10). RESULTS: Thirteen AIE patients were included, 8 women (62%), median age of 52 years (range 23-73), and 6 (46%) with an autoimmune disease. AEA were observed in 11 cases (85%), but were also found in CD (7.7%), refractory celiac disease type 2 (16.7%), and EATL (20%). Ten patients (77%) were human leukocyte antigen DQ2.5 heterozygous. Total parenteral nutrition was required in 8 cases (62%). Steroids induced clinical remission in 8 cases (62%). Step-up therapy with rituximab, cyclosporine, infliximab, and cladribine in steroid-refractory patients was only moderately effective. Four patients died (31%), but 4 (31%) others are in long-term drug-free remission after receiving immunosuppressive treatment, including 1 patient who underwent autologous stem cell transplantation. DISCUSSION: Adult-onset AIE is a rare but severe enteropathy that occurs in patients susceptible for autoimmune disease. Four patients (31%) died secondary to therapy-refractory malabsorption, while immunosuppressive therapy leads to a long-lasting drug-free remission in one-third of patients.

11.
United European Gastroenterol J ; 9(3): 332-342, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33887125

RESUMO

BACKGROUND: The gut fermentation syndrome (GFS), also known as the endogenous alcohol fermentation syndrome or auto brewery syndrome, is a rare and underdiagnosed medical condition where consumed carbohydrates are converted to alcohol by the microbiota in the gastrointestinal or urinary tract. The symptoms of GFS can have severe impact on patients' wellbeing and can have social and legal consequences. Unfortunately, not much is reported about GFS. The aim of this systematic review was to assess the evidence for GFS, causal micro-organisms, diagnostics, and possible treatments. METHODS: A protocol was developed prior to initiation of the systematic review (PROSPERO 207182). We performed a literature search for clinical studies on 1 September 2020 using PubMed and Embase. We included all clinical studies, including case reports that described the GFS. RESULTS: In total, 17 case reports were included, consisting of 20 patients diagnosed with GFS. The species that caused the GFS included Klebsiella pneumoniae, Candida albicans, C. glabrata, Saccharomyces cerevisiae, C. intermedia, C. parapsilosis, and C. kefyr. CONCLUSIONS: GFS is a rare but underdiagnosed disease in daily practice. The disease is mostly reported by Saccharomyces and Candida genera, and some cases were previously treated with antibiotics. Studies in Nonalcoholic Fatty Liver disease suggest a bacterial origin of endogenous alcohol-production, which might also be causal micro-organisms in GFS. Current treatments for GFS include antibiotics, antifungal medication, low carbohydrate diet, and probiotics. There might be a potential role of fecal microbiota transplant in the treatment of GFS.

12.
J Autoimmun ; 118: 102609, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33607573

RESUMO

Immune-mediated enteropathies are caused by excessive reactions of the intestinal immune system towards non-pathogenic molecules. Enteropathy leads to malabsorption-related symptoms and include (severe) chronic diarrhea, weight loss and vitamin deficiencies. Parenteral feeding and immunosuppressive therapy are needed in severe cases. Celiac disease has long been recognized as the most common immune-mediated enteropathy in adults, but the spectrum of immune-mediated enteropathies has been expanding. Histological and clinical features are sometimes shared among these enteropathies, and therefore it may be challenging to differentiate between them. Here, we provide an overview of immune-mediated enteropathies focused on clinical presentation, establishing diagnosis, immunopathogenesis, and treatment options.

13.
Gastrointest Endosc ; 93(6): 1411-1420.e18, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33069706

RESUMO

BACKGROUND AND AIMS: Since 2008, a plethora of research studies has compared the efficacy of water-assisted (aided) colonoscopy (WAC) and underwater resection (UWR) of colorectal lesions with standard colonoscopy. We reviewed and graded the research evidence with potential clinical application. We conducted a modified Delphi consensus among experienced colonoscopists on definitions and practice of water immersion (WI), water exchange (WE), and UWR. METHODS: Major databases were searched to obtain research reports that could potentially shape clinical practice related to WAC and UWR. Pertinent references were graded (Grading of Recommendations, Assessment, Development and Evaluation). Extracted data supporting evidence-based statements were tabulated and provided to respondents. We received responses from 55 (85% surveyed) experienced colonoscopists (37 experts and 18 nonexperts in WAC) from 16 countries in 3 rounds. Voting was conducted anonymously in the second and third round, with ≥80% agreement defined as consensus. We aimed to obtain consensus in all statements. RESULTS: In the first and the second modified Delphi rounds, 20 proposed statements were decreased to 14 and then 11 statements. After the third round, the combined responses from all respondents depicted the consensus in 11 statements (S): definitions of WI (S1) and WE (S2), procedural features (S3-S5), impact on bowel cleanliness (S6), adenoma detection (S7), pain score (S8), and UWR (S9-S11). CONCLUSIONS: The most important consensus statements are that WI and WE are not the same in implementation and outcomes. Because studies that could potentially shape clinical practice of WAC and UWR were chosen for review, this modified Delphi consensus supports recommendations for the use of WAC in clinical practice.


Assuntos
Adenoma , Água , Adenoma/diagnóstico , Adenoma/cirurgia , Colonoscopia , Consenso , Técnica Delfos , Humanos
14.
United European Gastroenterol J ; 9(2): 229-247, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33151137

RESUMO

BACKGROUND: Faecal microbiota transplantation is an emerging therapeutic option, particularly for the treatment of recurrent Clostridioides difficile infection. Stool banks that organise recruitment and screening of faeces donors are being embedded within the regulatory frameworks described in the European Union Tissue and Cells Directive and the technical guide to the quality and safety of tissue and cells for human application, published by the European Council. OBJECTIVE: Several European and international consensus statements concerning faecal microbiota transplantation have been issued. While these documents provide overall guidance, we aim to provide a detailed description of all processes that relate to the collection, handling and clinical application of human donor stool in this document. METHODS: Collaborative subgroups of experts on stool banking drafted concepts for all domains pertaining to stool banking. During a working group meeting in the United European Gastroenterology Week 2019 in Barcelona, these concepts were discussed and finalised to be included in our overall guidance document about faecal microbiota transplantation. RESULTS: A guidance document for all domains pertaining to stool banking was created. This document includes standard operating manuals for several processes involved with stool banking, such as handling of donor material, storage and donor screening. CONCLUSION: The implementation of faecal microbiota transplantation by stool banks in concordance with our guidance document will enable quality assurance and guarantee the availability of donor faeces preparations for patients.

15.
Dysphagia ; 36(3): 393-401, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32562140

RESUMO

Although barium swallow imaging is established in the investigation of Zenker's diverticulum (ZD), no agreed measurement protocol exists. We developed a protocol for measuring ZD dimensions and aimed to correlate measurements with symptoms and post-operative outcomes. This prospective study included patients with confirmed ZD who underwent flexible endoscopic septal division (FESD) between 2014 and 2018. ZD was confirmed on barium radiology with measurements reviewed by two consultant radiologists. Symptom severity pre- and post-FESD was measured using the Dysphagia, Regurgitation, Complications (DRC) scale. Regression analyses were conducted to identify dimensions associated with therapeutic success, defined as remission (DRC score ≤ 1) 6 months after index FESD. In total, 67 patients (mean age 74.3) were included. Interobserver reliability (intraclass correlation coefficients-ICCs) was greatest for pouch width (0.981) and pouch depth (0.934), but not oesophageal depth (0.018). Male gender (60.9%) was associated with larger pouch height (P = 0.008) and width (P = 0.004). A positive correlation was identified between baseline DRC score and pouch depth (ρ 0.326, P = 0.011), particularly the regurgitation subset score (ρ 0.330, P = 0.020). The index pouch depth was associated with FESD procedure time (rho 0.358, P = 0.041). Therapeutic success was achieved in 64.2% and was associated with shorter pouch height (median 14.5 mm vs. 19.0 mm, P = 0.030), pouch width (median 19.9 mm vs. 28.8 mm, P = 0.34) and cricopharyngeal length (median 20.2 mm vs. 26.3 mm, P = 0.036). ZD dimensions may be feasible and were evaluated using Barium radiology. Specific parameters appear to correlate with severity and post-FESD outcomes, which aid with pre-procedural planning.


Assuntos
Divertículo de Zenker , Idoso , Bário , Esofagoscopia , Feminino , Humanos , Masculino , Estudos Prospectivos , Reprodutibilidade dos Testes , Resultado do Tratamento , Divertículo de Zenker/diagnóstico por imagem , Divertículo de Zenker/cirurgia
16.
BMC Gastroenterol ; 20(1): 296, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32917155

RESUMO

BACKGROUND: Thioguanine (TG) is a thiopurine which has been used for patients with inflammatory bowel disease (IBD), who have failed azathioprine (AZA) or mercaptopurine (MP) due to adverse events or suboptimal response. Its widespread use has been hampered due to concerns about nodular regenerative hyperplasia (NRH) of the liver. The aim of this study was to investigate the long-term efficacy and safety of low-dose TG therapy in IBD patients failing AZA and MP. METHODS: A retrospective multicentre study was performed in IBD patients who failed prior treatment with conventional thiopurines with or without following immunomodulation (thiopurine-allopurinol, biologicals, methotrexate, tacrolimus) and were subsequently treated with TG as rescue monotherapy between 2003 and 2019 at three hospitals in the United Kingdom. Clinical response, adverse events, laboratory results, imaging and liver biopsies were retrospectively collected. RESULTS: A total of 193 patients (57% female and 64% Crohn's disease) were included, with a median daily TG dose of 20 mg (range: 20-40 mg), a median treatment duration of 23 months (IQR 10-47) and a median follow-up of 36 months (IQR 22-53). The clinical response rate at 12 months was 65 and 54% remained on TG until the end of follow-up. Adverse events consisted primarily of elevated liver tests (6%), myelotoxicity (7%) and rash (5%). NRH was histologically diagnosed in two patients and two other patients (1%) developed non-cirrhotic portal hypertension. The median 6-TGN and TPMT levels were 953 pmol/8 × 105 RBC (IQR 145-1761) and 47 mu/L (IQR 34.5-96). CONCLUSIONS: Long-term follow-up suggests that TG can be an effective and well-tolerated therapy in more than half of difficult-to-treat and multi-therapy failing IBD patients. Findings of this study indicate that TG can be used safely and the occurrence of hepatotoxicity was low. The incidence rate of NRH was within the background incidence.


Assuntos
Doenças Inflamatórias Intestinais , Preparações Farmacêuticas , Azatioprina/efeitos adversos , Feminino , Humanos , Imunossupressores/efeitos adversos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Masculino , Mercaptopurina , Estudos Retrospectivos , Tioguanina/efeitos adversos , Resultado do Tratamento , Reino Unido
17.
JGH Open ; 4(4): 743-748, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32782965

RESUMO

Background: Structural disorders of the hypopharynx can lead to dysphagia-related morbidity. Endoscopic therapy in this area, for example, myotomy for Zenker's diverticulum (ZD), has traditionally been performed under general anesthesia (GA). We have developed a two-stage sedation process, which is used along with high-flow nasal oxygen therapy (HFNOT) to facilitate endoscopic hypopharyngeal procedures. Methods: In this prospective, single-center study, patients undergoing endoscopic procedures between June 2016 and March 2018 were included. All endoscopies were performed with propofol and/or remifentanil and supported with HFNOT. In patients with ZD, the diverticulum and stomach were cleared of debris under conscious sedation to reduce the risk of aspiration, before sedation was deepened to facilitate myotomy. Sedation-related adverse events were recorded. Results: A total of 50 patients were included for analysis (mean age of 71.1, range 31-93; 58% male); 48% were categorized as American Society of Anesthesiologists (ASA) Grade III and 6% as Grade IV. The median procedure time was 20 min. Of patients, 83% were sedated with both propofol and remifentanil using a target-controlled infusion under specialist anesthetic supervision. Sedation-related adverse events included transient hypotension (38%), bradycardia (8%), and hypoxia (8%). No procedures were abandoned due to complications, and no patients required conversion to GA. Patients achieved full postprocedure recovery from sedation after a median duration of 5 min. Conclusions: HFNOT is a useful adjunct to two-stage sedation, which can enable high-risk patients to safely undergo deep sedation during hypopharyngeal endoscopic procedures.

18.
Endosc Int Open ; 8(7): E985-E989, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32617403

RESUMO

Background and aim As the post-peak phase of the epidemic is approaching, there is an urgent need of an action plan to help resume endoscopy activity. To manage the Covid-19 pandemic-imposed backlog of postponed colonoscopy examinations, an efficient approach is needed. The practice of on-demand sedation with benzodiazepines and/or opiates will allow most patients to complete a water-aided examination with minimal or no sedation. Other methods reported to minimize patient discomfort during colonoscopy can be used, in addition to water-aided techniques. Unsedated or minimally sedated patients who do not require recovery or require a shorter one allow rapid turnaround. The practice obviates the need for assistance with deep sedation from anesthesiologists, who may be in short supply. Trainee education in water-aided colonoscopy has been demonstrated to confer benefits. This review provides some insights into the impact of Covid-19 on endoscopy services, challenges ahead, and possible solutions to help recovery of colonoscopy work and training.

19.
Dis Esophagus ; 33(11)2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-32266391

RESUMO

OBJECTIVES: Flexible endoscopic septum division is an established treatment for Zenker's diverticulum (ZD); however, long-term outcome data are lacking. We aimed to evaluate the long-term efficacy of flexible endoscopic septal division (FESD) using the stag beetle knife for ZD and identify predictors of symptom recurrence. METHODS: Patients undergoing the procedure between 2013 and 2018 were prospectively enrolled. Procedures were performed by a single operator. Symptom severity pre- and postprocedure was recorded using the dysphagia, regurgitation, and complications scale. Symptom recurrence was defined as a total score > 1 after the index procedure. Time-to-event analyses were performed using Kaplan-Meier plots, with multivariable analyses performed using Cox regression models. RESULTS: Altogether, 65 patients (mean age 74.0 years, 60% male) were included. Previous stapling had been performed in 44.6% of patients. Over the mean posttreatment follow-up period of 19 months, 5.6% of the treatment naïve group and 34.5% of the recurrent group underwent repeated FESD (P = 0.003), with rates of symptom remission and improvement of 75.4% and 92.7%, respectively. Recurrence at 48 months was higher in patients with recurrent ZD (84.7%) than in treatment-naïve patients (10.7%). On multivariable analysis, recurrent disease (hazard ratio [HR] 20.8, P = 0.005) and younger age (HR 0.96/year, P = 0.047) were associated with symptom recurrence. CONCLUSIONS: In patients with treatment-naïve ZD, flexible endoscopic septal division is safe and provides durable symptom remission. However, in patients with poststapling recurrence, the risk of recurrence is high and time-dependent.


Assuntos
Besouros , Transtornos de Deglutição , Divertículo de Zenker , Idoso , Animais , Transtornos de Deglutição/etiologia , Esofagoscopia , Feminino , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Divertículo de Zenker/cirurgia
20.
Expert Opin Drug Metab Toxicol ; 16(2): 111-123, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32090622

RESUMO

Introduction: In the 1950s, thioguanine (TG), a thiopurine-derivative together with azathioprine (AZA) and mercaptopurine (MP), were developed for the treatment of childhood leukemia. Over the years, the use of TG was also explored for other, mainly immune-mediated and inflammatory, diseases such as in the field of dermatology and rheumatology (e.g. psoriasis, systemic lupus erythematosus (SLE)) and gastroenterology and hepatology (e.g. inflammatory bowel diseases (IBD), autoimmune hepatitis).Areas covered: This review provides a comprehensive overview of all the clinical uses of TG and describes its mechanism of action, pharmacokinetic/pharmacodynamic features, and toxicity.Expert opinion: Thioguanine has shown beneficial clinical effects in hematological (particularly leukemia) and several immune-inflammatory diseases including psoriasis, SLE, polycythemia vera, Churg-Strauss syndrome, IBD, collagenous sprue, refractory celiac disease, and autoimmune hepatitis. Thioguanine is not effective in treating solid-cancers. At relatively low dosages, i.e. 0.2- 0.3mg/kg/day or 20 mg/day, TG has a favorable risk-benefit ratio and is a safe and effective drug in the long-term treatment of amongst other IBD patients. Thioguanine toxicity, especially myelotoxicity, and hepatotoxicity, including nodular regenerative hyperplasia (NRH) of the liver, is limited when dosed adequately. The occurrence of NRH appears dose-dependent and has been especially described during high dose TG above 40 mg/day.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Tioguanina/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/farmacocinética , Relação Dose-Resposta a Droga , Humanos , Leucemia/tratamento farmacológico , Tioguanina/efeitos adversos , Tioguanina/farmacocinética
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