Misconceptions are common in the care of patients with inflammatory bowel disease(IBD).In this paper,we state the most commonly found misconceptions in clinical practice and deal with the use of 5-aminosalicylates and...Misconceptions are common in the care of patients with inflammatory bowel disease(IBD).In this paper,we state the most commonly found misconceptions in clinical practice and deal with the use of 5-aminosalicylates and thiopurines,to review the related scientificevidence,and make appropriate recommendations.Prevention of errors needs knowledge to avoid making such errors through ignorance.However,the amount of knowledge is increasing so quickly that one new danger is an overabundance of information.IBD is a model of a very complex disease and our goal with this review is to summarize the key evidence for the most common daily clinical problems.With regard to the use of 5-aminosalicylates,the best practice may to be consider abandoning the use of these drugs in patients withsmall bowel Crohn's disease.The combined approach with oral plus topical 5-aminosalicylates should be the first-line therapy in patients with active ulcerative colitis;once-daily treatment should be offered as a first choice regimen due to its better compliance and higher efficacy.With regard to thiopurines,they seem to be as effective in ulcerative colitis as in Crohn's disease.Underdosing of thiopurines is a form of undertreatment.Thiopurines should probably be continued indefinitely because their withdrawal is associated with a high risk of relapse.Mercaptopurine is a safe alternative in patients with digestive intolerance or hepatotoxicity due to azathioprine.Finally,thiopurine methyltransferase(TPMT)screening cannot substitute for regular monitoring because the majority of cases of myelotoxicity are not TPMT-related.展开更多
Inflammatory bowel disease (IBD) includes two entities, Crohn’s disease and ulcerative colitis. Both are chronic conditions with frequent complications and surgical procedures and a great impact on patient’s quality...Inflammatory bowel disease (IBD) includes two entities, Crohn’s disease and ulcerative colitis. Both are chronic conditions with frequent complications and surgical procedures and a great impact on patient’s quality of life. The thiopurine antimetabolites azathioprine and 6-mercaptopurine are widely used in IBD patients. Current indications include maintenance therapy, steroid-dependant disease, fistula closure, prevention of infliximab immunogenicity and prevention of Crohn’s disease recurrence. Surprisingly, the wide use of immunosuppressants in the last decades has not decreased the need of surgery, probably because these treatments are introduced at too late stages in disease course. An earlier use of immunossupressants is now advocated by some authors. The rational includes: (1) failure to modify IBD natural history of present therapeutic approach, (2) demonstration that azathioprine can induce mucosal healing, a relevant prognostic factor for Crohn’s disease and ulcerative colitis, and (3) demonstration that early immunossupression has a very positive impact on pediatric, recently diagnosed Crohn’s disease patients. We are now awaiting the results of new studies, to clarify the contribution of azathioprine, as compared to infliximab (SONIC Study), and to demonstrate the usefulness of azathioprine in recently diagnosed adult Crohn’s disease patients (AZTEC study).展开更多
Patients with inflammatory bowel disease have normal life expectancy and, due to modern immunosuppressive therapies, also a normal quality of life. Since mostly young people are affected, their social behaviour suits ...Patients with inflammatory bowel disease have normal life expectancy and, due to modern immunosuppressive therapies, also a normal quality of life. Since mostly young people are affected, their social behaviour suits this environment. Alcohol binging is an increasingly disturbing factor among young people. We describe a patient with Crohn's disease, treated with azathioprine, who developed peliosis hepatis after three epsiodes of alcohol binging. Liver toxicity was not observed previously during the course of the treatment. Azathioprine-induced peliosis hepatis is thought to be idiosyncratic in humans. From animal studies, however, it is clear that hepatic depletion of glutathione leads to azathioprine toxicity to the sinusoidal endothelial cells. Damage of these cells causes peliosis hepatis. Since alcohol binging leads to hepatic glutathione depletion, we conclude that in our patient the episodes of binging have reduced liver gluathione content and therefore this has increased azathioprine toxicity causing peliosis hepatis. The problem of alcohol binging has not yet been addressed in IBD patients undertaking immunosuppressive therapy. This should be reviewed in future considerations regarding patients advice.展开更多
AIM： To evaluate the role of azathioprine （AZA） in Indian patients with ulcerative colitis over longer duration of time. METHODS： One hundred fifty six patients with ulcerative colitis who were treated with AZA fr...AIM： To evaluate the role of azathioprine （AZA） in Indian patients with ulcerative colitis over longer duration of time. METHODS： One hundred fifty six patients with ulcerative colitis who were treated with AZA from January 1995 to December 2003 were reviewed. The indications for its use were as follows： （1） steroid dependent and steroid refractory disease; （2） Azathioprine monotherapy for na＇fve patients with severe disease; and （3） combination therapy （AZA ＋ sulfasalazine or 5-aminosalicylates） for naive patients with severe disease. The data included patient and disease demographics, efficacy and toxicity profile of AZA. Patients with a minimum duration of 6 mo use of AZA were included in this report. RESULTS： Of a total of 156 patients treated with AZA, 45 were excluded from analysis for the following reasons- （follow up less than 6 mo, n = 9; poor follow up, n = 18; adverse affects, n = 18）. In steroid refractory/dependent group the mean number of relapses prior to and post initiation of AZA therapy were 3.28 （± 0.81） and 0.94 （± 0.29） respectively. Discontinuation of steroids could be accomplished in 12 of the 15 steroid dependent patients. The proportion of patients with sustained remission of 1, 2, 3, 4 and 5 years duration were calculated. Eighteen patients experienced adverse effects necessitating withdrawal of AZA （pancreatitis, n = 7; hepatitis, n = 3; gastrointestinal intolerance, n = 2; alopecia, n = 2; and hematological, n = 4） while 13 patients needed dose reduction or temporary withdrawal of the drug. CONCLUSION： Azathioprine is well tolerated and has therapeutic benefits lasting as long as 4 years. Adverse effects such as pancreatitis, hepatitis, cytopenias and gastrointestinal symptoms do occur but are controlled by drug withdrawal only.展开更多
Systemic corticosteroids represent the standard treatment for autoimmune pancreatitis with IgG4-associated cholangitis.For steroid-dependent disease,azathioprine has been used for maintenance of remission.Mycophenolat...Systemic corticosteroids represent the standard treatment for autoimmune pancreatitis with IgG4-associated cholangitis.For steroid-dependent disease,azathioprine has been used for maintenance of remission.Mycophenolate mofetil has been used for transplant immunosuppression and more recently for autoimmune hepatitis;however,there are no case reports to date on the use of mycophenolate mofetil in adult patients with autoimmune pancreatitis.A patient with IgG4-mediated autoimmune pancreatitis and IgG4-associated cholangitis refractory to steroids and intolerant of azathioprine was treated with mycophenolate mofetil,which inhibits de novo guanosine synthesis and blockade of both B and T lymphocyte production.Introduction of mycophenolate mofetil and uptitration to 1000 mg by mouth twice daily over a treatment period of 4 mo was associated with improvement in the patient's energy level and blood glucose control and was not associated with any adverse events.The patient was managed without a biliary stent.However,there was a return of symptoms,jaundice,increase in transaminases,and hyperbilirubinemia when the prednisone dose reached 11 mg per day.In the first report of mycophenolate mofetil use in an adult patient with IgG4-associated autoimmune pancreatitis and IgG4-associated cholangitis,the introduction of mycophenolate mofetil was safe and well-tolerated without adverse events,but it did not enable discontinuation of the steroids.Mycophenolate mofetil and other immunomodulatory therapies should continue to be studied for maintenance of remission in the large subset of patients with refractory or recurrent autoimmune pancreatitis.展开更多
文摘Misconceptions are common in the care of patients with inflammatory bowel disease(IBD).In this paper,we state the most commonly found misconceptions in clinical practice and deal with the use of 5-aminosalicylates and thiopurines,to review the related scientificevidence,and make appropriate recommendations.Prevention of errors needs knowledge to avoid making such errors through ignorance.However,the amount of knowledge is increasing so quickly that one new danger is an overabundance of information.IBD is a model of a very complex disease and our goal with this review is to summarize the key evidence for the most common daily clinical problems.With regard to the use of 5-aminosalicylates,the best practice may to be consider abandoning the use of these drugs in patients withsmall bowel Crohn's disease.The combined approach with oral plus topical 5-aminosalicylates should be the first-line therapy in patients with active ulcerative colitis;once-daily treatment should be offered as a first choice regimen due to its better compliance and higher efficacy.With regard to thiopurines,they seem to be as effective in ulcerative colitis as in Crohn's disease.Underdosing of thiopurines is a form of undertreatment.Thiopurines should probably be continued indefinitely because their withdrawal is associated with a high risk of relapse.Mercaptopurine is a safe alternative in patients with digestive intolerance or hepatotoxicity due to azathioprine.Finally,thiopurine methyltransferase(TPMT)screening cannot substitute for regular monitoring because the majority of cases of myelotoxicity are not TPMT-related.
基金Grants from Ministerio de Educación y Ciencia(SAF2005-00280) to MS
文摘Inflammatory bowel disease (IBD) includes two entities, Crohn’s disease and ulcerative colitis. Both are chronic conditions with frequent complications and surgical procedures and a great impact on patient’s quality of life. The thiopurine antimetabolites azathioprine and 6-mercaptopurine are widely used in IBD patients. Current indications include maintenance therapy, steroid-dependant disease, fistula closure, prevention of infliximab immunogenicity and prevention of Crohn’s disease recurrence. Surprisingly, the wide use of immunosuppressants in the last decades has not decreased the need of surgery, probably because these treatments are introduced at too late stages in disease course. An earlier use of immunossupressants is now advocated by some authors. The rational includes: (1) failure to modify IBD natural history of present therapeutic approach, (2) demonstration that azathioprine can induce mucosal healing, a relevant prognostic factor for Crohn’s disease and ulcerative colitis, and (3) demonstration that early immunossupression has a very positive impact on pediatric, recently diagnosed Crohn’s disease patients. We are now awaiting the results of new studies, to clarify the contribution of azathioprine, as compared to infliximab (SONIC Study), and to demonstrate the usefulness of azathioprine in recently diagnosed adult Crohn’s disease patients (AZTEC study).
文摘Patients with inflammatory bowel disease have normal life expectancy and, due to modern immunosuppressive therapies, also a normal quality of life. Since mostly young people are affected, their social behaviour suits this environment. Alcohol binging is an increasingly disturbing factor among young people. We describe a patient with Crohn's disease, treated with azathioprine, who developed peliosis hepatis after three epsiodes of alcohol binging. Liver toxicity was not observed previously during the course of the treatment. Azathioprine-induced peliosis hepatis is thought to be idiosyncratic in humans. From animal studies, however, it is clear that hepatic depletion of glutathione leads to azathioprine toxicity to the sinusoidal endothelial cells. Damage of these cells causes peliosis hepatis. Since alcohol binging leads to hepatic glutathione depletion, we conclude that in our patient the episodes of binging have reduced liver gluathione content and therefore this has increased azathioprine toxicity causing peliosis hepatis. The problem of alcohol binging has not yet been addressed in IBD patients undertaking immunosuppressive therapy. This should be reviewed in future considerations regarding patients advice.
文摘AIM： To evaluate the role of azathioprine （AZA） in Indian patients with ulcerative colitis over longer duration of time. METHODS： One hundred fifty six patients with ulcerative colitis who were treated with AZA from January 1995 to December 2003 were reviewed. The indications for its use were as follows： （1） steroid dependent and steroid refractory disease; （2） Azathioprine monotherapy for na＇fve patients with severe disease; and （3） combination therapy （AZA ＋ sulfasalazine or 5-aminosalicylates） for naive patients with severe disease. The data included patient and disease demographics, efficacy and toxicity profile of AZA. Patients with a minimum duration of 6 mo use of AZA were included in this report. RESULTS： Of a total of 156 patients treated with AZA, 45 were excluded from analysis for the following reasons- （follow up less than 6 mo, n = 9; poor follow up, n = 18; adverse affects, n = 18）. In steroid refractory/dependent group the mean number of relapses prior to and post initiation of AZA therapy were 3.28 （± 0.81） and 0.94 （± 0.29） respectively. Discontinuation of steroids could be accomplished in 12 of the 15 steroid dependent patients. The proportion of patients with sustained remission of 1, 2, 3, 4 and 5 years duration were calculated. Eighteen patients experienced adverse effects necessitating withdrawal of AZA （pancreatitis, n = 7; hepatitis, n = 3; gastrointestinal intolerance, n = 2; alopecia, n = 2; and hematological, n = 4） while 13 patients needed dose reduction or temporary withdrawal of the drug. CONCLUSION： Azathioprine is well tolerated and has therapeutic benefits lasting as long as 4 years. Adverse effects such as pancreatitis, hepatitis, cytopenias and gastrointestinal symptoms do occur but are controlled by drug withdrawal only.
基金Supported by Department of Medicine,Emory University
文摘Systemic corticosteroids represent the standard treatment for autoimmune pancreatitis with IgG4-associated cholangitis.For steroid-dependent disease,azathioprine has been used for maintenance of remission.Mycophenolate mofetil has been used for transplant immunosuppression and more recently for autoimmune hepatitis;however,there are no case reports to date on the use of mycophenolate mofetil in adult patients with autoimmune pancreatitis.A patient with IgG4-mediated autoimmune pancreatitis and IgG4-associated cholangitis refractory to steroids and intolerant of azathioprine was treated with mycophenolate mofetil,which inhibits de novo guanosine synthesis and blockade of both B and T lymphocyte production.Introduction of mycophenolate mofetil and uptitration to 1000 mg by mouth twice daily over a treatment period of 4 mo was associated with improvement in the patient's energy level and blood glucose control and was not associated with any adverse events.The patient was managed without a biliary stent.However,there was a return of symptoms,jaundice,increase in transaminases,and hyperbilirubinemia when the prednisone dose reached 11 mg per day.In the first report of mycophenolate mofetil use in an adult patient with IgG4-associated autoimmune pancreatitis and IgG4-associated cholangitis,the introduction of mycophenolate mofetil was safe and well-tolerated without adverse events,but it did not enable discontinuation of the steroids.Mycophenolate mofetil and other immunomodulatory therapies should continue to be studied for maintenance of remission in the large subset of patients with refractory or recurrent autoimmune pancreatitis.
