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
AIM: To determine the tolerability and safety profile of a low-dose maintenance therapy with 6-TG in azathioprine (AZA) or 6-mercaptopurine (6-MP) intolerant inflammatory bowel disease (IBD) patients over a treatment ...AIM: To determine the tolerability and safety profile of a low-dose maintenance therapy with 6-TG in azathioprine (AZA) or 6-mercaptopurine (6-MP) intolerant inflammatory bowel disease (IBD) patients over a treatment period of at least 1 year.METHODS: Database analysis.RESULTS: Twenty out of ninety-five (21%) patients discontinued 6-TG (mean dose 24.6 mg; mean 6-TGN level 540 pmol/8×108 RBC) within 1 year. Reasons for discontinuation were GI complaints (31%), malaise (15%)and hepatotoxicity (15%). Hematological events occurred in three patients, one discontinued treatment. In the 6-TG-tolerant group, 9% (7/75) could be classified as hepatotoxicity. An abdominal ultrasound was performed in 54% of patients, one patient had splenomegaly.CONCLUSION: The majority of AZA or 6-MP-intolerant IBD patients (79%) is able to tolerate maintenance treatment with 6-TG (dosages between 0.3 and 0.4 mg/kg per d). 6-TG may still be considered as an escape maintenance immunosuppressant in this difficult to treat group of patients, taking into account potential toxicity and efficacy of other alternatives. The recently reported hepatotoxicity is worrisome and 6-TG should therefore be administered only in prospective trials.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
The Crohn's disease activity index(CDAI) has been commonly used to assess the effects of treatment with different agents in Crohn's disease(CD).However these studies may be compromised,if the results compared ...The Crohn's disease activity index(CDAI) has been commonly used to assess the effects of treatment with different agents in Crohn's disease(CD).However these studies may be compromised,if the results compared to a placebo or standard therapy group(in the absence of a placebo) substantially differ from the expected response.In addition,significan concerns have been raised regarding the reliability and validity of the CDAI.Reproducibility of the CDAI may be limited as significant inter-observer error has been recorded,even if measurements are done by experienced clinicians with expertise in the diagnosis and treatment of CD.Finally,many CDAI endpoints are open to subjective interpretation and have the potential for manipulation.This is worrisome as there is the potential for significant financial gain if the results of a clinical trial appear to provide a positive result.Physicians caring for patients should be concerned about the positive results in clinica trials that are sponsored by industry,even if the trials involve respected centers and the results appear in highly ranked medical journals.展开更多
AIM:To investigate the efficacy of 6-mercaptopurine (6-MP) in cases of azathioprine (AZA) hypersensitivity in patients with inflammatory bowel disease. METHODS: Twenty nine previously confirmed Crohn’s disease (CD) (...AIM:To investigate the efficacy of 6-mercaptopurine (6-MP) in cases of azathioprine (AZA) hypersensitivity in patients with inflammatory bowel disease. METHODS: Twenty nine previously confirmed Crohn’s disease (CD) (n = 14) and ulcerative colitis (UC) (n = 15) patients with a known previous (AZA) hypersensitivity reaction were studied prospectively. The 6-MP doses were gradually increased from 0.5 up to 1.0-1.5 mg/kg per day. Clinical activity indicies (CDAI/CAI), laboratory variables and daily doses of oral 5-ASA, corticosteroids, and 6-MP were assessed before and in the first, sixth and twelfth months of treatment. RESULTS: In 9 patients, 6-MP was withdrawn in the first 2 wk due to an early hypersensitivity reaction. Medication was ineffective within 6 mo in 6 CD patients, and myelotoxic reaction was observed in two. Data were evaluated at the end of the sixth month in 12 (8 UC, 4 CD) patients, and after the first year in 9 (6 UC, 3 CD) patients. CDAI decreased transiently at the end of the sixth month, but no significant changes were observed in the CDAI or the CAI values at the end of the year. Leukocyte counts (P = 0.01), CRP (P = 0.02), and serum iron (P = 0.05) values indicated decreased inflammatory reactions, especially in the UC patients at the end of the year, making the possibility to taper oral steroid doses. CONCLUSION: About one-third of the previously AZA- intolerant patients showed adverse effects on taking 6MP. In our series, 20 patients tolerated 6MP, but it was ineffective in 8 CD cases, and valuable mainly in ulcerative colitis patients.展开更多
Although systemic steroids are highly efficacious in ulcerative colitis (UC), failure to respond to steroids still poses an important challenge to the surgeon and physician alike. Even if the life time risk of a fulmi...Although systemic steroids are highly efficacious in ulcerative colitis (UC), failure to respond to steroids still poses an important challenge to the surgeon and physician alike. Even if the life time risk of a fulminant UC flare is only 20%, this condition is potentially life threatening and should be managed in hospital. If patients fail 3 to 5 d of intravenous corticosteroids and optimal supportive care, they should be considered for any of three options: intravenous cyclosporine (2 mg/kg for 7 d, and serum level controlled), infliximab (5 mg/kg Ⅳ, 0-2-6 wk) or total colectomy. The choice between these three options is a medical- surgical decision based on clinical signs, radiological and endoscopic findings and blood analysis (CRP, serum albumin). Between 65 and 85% of patients will initially respond to cyclosporine and avoid colectomy on the short term. Over 5 years only 50% of initial responders avoid colectomy and outcomes are better in patients naive to azathioprine (bridging strategy). The data on infliximab as a medical rescue in fulminant colitis are more limited although the efficacy of this anti tumor necrosis factor (TNF) monoclonal antibody has been demonstrated in a controlled trial. Controlled data on the comparative efficacy of cyclosporine and infliximab are not available at this moment. Both drugs are immunosuppressants and are used in combination with steroids and azathioprine, which infers a risk of serious, even fatal, opportunistic infections. Therefore, patients not responding to these agents within 5-7 d should be considered for colectomy and responders should be closely monitored for infections.展开更多
The early hypersensitivity reaction and late bone marrow depression are well-known side-effects of azathioprine, whereas interstitial pneumonia is a rare complication. A 40-year old male patient had been treated with ...The early hypersensitivity reaction and late bone marrow depression are well-known side-effects of azathioprine, whereas interstitial pneumonia is a rare complication. A 40-year old male patient had been treated with azathioprine in consequence of extensive ulcerative colitis for 10 years. He then complained of 7 d of fever, cough and catarrhal signs, without symptoms of active colitis. Opportunistic infections were ruled out. The chest X-ray, CT and lung biopsy demonstrated the presence of interstitial inflammation. Azathioprine therapy was discontinued as a potential source of the pulmonary infiltrate. In response to steroid therapy, and intensive care, the pulmonary infiltrate gradually decreased within 4 wk. Three months later, his ulcerative colitis relapsed, and ileo-anal pouch surgery was performed. In cases of atypical pneumonia, without a proven infection, azathioprine-associated interstitial pneumonitis may be present, which heals after withdrawal of the drug.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 f ifty six patients with ulcerative colitis who were treated with AZA from ...AIM: To evaluate the role of azathioprine (AZA) in Indian patients with ulcerative colitis over longer duration of time. METHODS: One hundred f ifty 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?ve patients with severe disease; and (3) combination therapy (AZA + sulfasalazine or 5-aminosalicylates) for na?ve patients with severe disease. The data included patient and disease demographics, effi cacy and toxicity profi le 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 hastherapeutic benefi ts 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
Azathioprine is currently the key drug in the maintenance treatment of inflammatory bowel diseases. However, there are still some practical issues to be resolved: one is how long we must maintain the drug. Given that ...Azathioprine is currently the key drug in the maintenance treatment of inflammatory bowel diseases. However, there are still some practical issues to be resolved: one is how long we must maintain the drug. Given that inflammatory bowel diseases are to date chronic, non-curable conditions, treatment should be indefinite and only the loss of efficacy or the appearance of serious side effects may cause withdrawal. As regards to efficacy and their maintenance over time, evidence supports the continuous usefulness of the drug in the long term: in fact its withdrawal very substantially increases the risk of relapse. About side effects, azathioprine is a relatively well tolerated drug and even indefinite use seems safe. The main theoretical risks of prolonged use would be the myelotoxicity, hepatotoxicity, and the development of cancer. In fact, serious bone marrow suppression or serious liver damage are uncommon, and can be minimized with proper use of the drug. Recent metanalysis suggests that the risk of lymphoma is real, but the individual risk is rather low, and decision analysis suggests a favorable benefit/risk ratio in the long term. Therefore, in patients with inflammatory bowel diseases in whom azathioprine is effective and well tolerated, the drug should not be stopped. This recommendation concerns the use of azathioprine as a single maintenance drug, and is not necessarily applicable to patients receiving concomitant biological therapy.展开更多
Background: Autoimmune hepatitis (AIH) is an immune mediated chronic liver diseasewith a prevalence of 17 cases/100,000. Resistance to the standard treatment of AIH (prednisone and azathioprine) occurs in 15%to 20%. T...Background: Autoimmune hepatitis (AIH) is an immune mediated chronic liver diseasewith a prevalence of 17 cases/100,000. Resistance to the standard treatment of AIH (prednisone and azathioprine) occurs in 15%to 20%. There is currently no standard treatment of patients with steroid refractory AIH. Goals: Determine the efficacy of tacrolimus in the treatment of steroid refractory AIH. Methods: This is a retrospective study evaluating the efficacy of Tacrolimus in the treatment of steroid refractory AIH. Results: Between October 1998 and February 2002, 11 patients with steroid refractory AIH were treated with tacrolimus. Mean age was 63 years. Median duration of steroid treatment before starting tacrolimus was 9 months. Median duration of tacrolimus treatment was 25 months. Median follow up period was 16 months. Median baseline ALT, AST were 77 U/L and 68 U/L and became 21 U/L and 32 U/L respectively at end of follow up (P = 0.005 and 0.01 respectively). Significant weight reduction was seen in all patients (P = 0.02). Tacrolimus treatment was safe and well tolerated. Conclusion: Use of low dose tacrolimus led to successful biochemical and histologic remission and weaning off prednisone in patients with steroid refractory AIH. This data supports further studies in evaluating the use of tacrolimus in the treatment of AIH.展开更多
A 55-year-old White woman was first seen in July 1995 with ulceration of the oral mucosa, including the gingiva, labial mucosa, gums, palate and tongue, as well as erosions and blisters on the trunk. A biopsy showed a...A 55-year-old White woman was first seen in July 1995 with ulceration of the oral mucosa, including the gingiva, labial mucosa, gums, palate and tongue, as well as erosions and blisters on the trunk. A biopsy showed a suprabasal blister with acantholysis. Direct immunofluorescence was positive for intercellular deposits of IgG and C3, and indirect immunofluorescence was positive for intercellular antibodies at a titer of 160. The patient was diagnosed as having pemphigus vulgaris and treated with prednisone 1-1.5 mg/kg/day from 1995 until 1998, but no response was observed (the disease continued to be active with the formation of new lesions. The patent develoyd a number of steroid-complications including diabetes, osteoporosis, Cushing syndrome, hypertension and high-output cardiac failure, and required repeated hospitalization. In August 1998 she was started on azathioprine 100-150 mg/day and continued on prednisone 1 mg/kg/day. One year later, in August 1999, the disease was still active with new lesion formation and persistent oral erosions and dysphagia, despite persistent therapywith azathioprine 150 mg/day and prednisone 1mg/kg/day. Because of the disease severity and the lack of a reponse to treatment, in October 1999 the patient was started on thalidomide therapy 100 mg/day (1.7 mg/kg/day) and continued the prednisone treatment at 1 mg/kg /day together with azathioprine 150 mg/day (2.7 mg/kg/day). There was a good response, with clearing of all oral lesions in 20 days. The prednisone dose was gradually reduced and was discontinued in May 2000; azathioprine was gradually reduced to 50 mg 3 times/week (0.35 mg/kg/day). Thalidomide was continued at a dose of 100 mg/day. The patient was in total clinical remission, being free of both old and new lesions, for the next 14 months, when the thalidomide treatmentwas discontinued as a result of side-effects, including weakness in the legs and paresthesis of the fingers. After the discontinuance of treatment with thalidomide, severe lesions returned. Thalidomide was reintroduced, at 100 mg/day. After 2 months the patient entered total clinical remission and on the last occasion on which she was seen, in May 2003, was found to have remained clear of lesions. The patient continues to take thalidomide at 100 mg/day.展开更多
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AIM: To determine the tolerability and safety profile of a low-dose maintenance therapy with 6-TG in azathioprine (AZA) or 6-mercaptopurine (6-MP) intolerant inflammatory bowel disease (IBD) patients over a treatment period of at least 1 year.METHODS: Database analysis.RESULTS: Twenty out of ninety-five (21%) patients discontinued 6-TG (mean dose 24.6 mg; mean 6-TGN level 540 pmol/8×108 RBC) within 1 year. Reasons for discontinuation were GI complaints (31%), malaise (15%)and hepatotoxicity (15%). Hematological events occurred in three patients, one discontinued treatment. In the 6-TG-tolerant group, 9% (7/75) could be classified as hepatotoxicity. An abdominal ultrasound was performed in 54% of patients, one patient had splenomegaly.CONCLUSION: The majority of AZA or 6-MP-intolerant IBD patients (79%) is able to tolerate maintenance treatment with 6-TG (dosages between 0.3 and 0.4 mg/kg per d). 6-TG may still be considered as an escape maintenance immunosuppressant in this difficult to treat group of patients, taking into account potential toxicity and efficacy of other alternatives. The recently reported hepatotoxicity is worrisome and 6-TG should therefore be administered only in prospective trials.
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The Crohn's disease activity index(CDAI) has been commonly used to assess the effects of treatment with different agents in Crohn's disease(CD).However these studies may be compromised,if the results compared to a placebo or standard therapy group(in the absence of a placebo) substantially differ from the expected response.In addition,significan concerns have been raised regarding the reliability and validity of the CDAI.Reproducibility of the CDAI may be limited as significant inter-observer error has been recorded,even if measurements are done by experienced clinicians with expertise in the diagnosis and treatment of CD.Finally,many CDAI endpoints are open to subjective interpretation and have the potential for manipulation.This is worrisome as there is the potential for significant financial gain if the results of a clinical trial appear to provide a positive result.Physicians caring for patients should be concerned about the positive results in clinica trials that are sponsored by industry,even if the trials involve respected centers and the results appear in highly ranked medical journals.
文摘AIM:To investigate the efficacy of 6-mercaptopurine (6-MP) in cases of azathioprine (AZA) hypersensitivity in patients with inflammatory bowel disease. METHODS: Twenty nine previously confirmed Crohn’s disease (CD) (n = 14) and ulcerative colitis (UC) (n = 15) patients with a known previous (AZA) hypersensitivity reaction were studied prospectively. The 6-MP doses were gradually increased from 0.5 up to 1.0-1.5 mg/kg per day. Clinical activity indicies (CDAI/CAI), laboratory variables and daily doses of oral 5-ASA, corticosteroids, and 6-MP were assessed before and in the first, sixth and twelfth months of treatment. RESULTS: In 9 patients, 6-MP was withdrawn in the first 2 wk due to an early hypersensitivity reaction. Medication was ineffective within 6 mo in 6 CD patients, and myelotoxic reaction was observed in two. Data were evaluated at the end of the sixth month in 12 (8 UC, 4 CD) patients, and after the first year in 9 (6 UC, 3 CD) patients. CDAI decreased transiently at the end of the sixth month, but no significant changes were observed in the CDAI or the CAI values at the end of the year. Leukocyte counts (P = 0.01), CRP (P = 0.02), and serum iron (P = 0.05) values indicated decreased inflammatory reactions, especially in the UC patients at the end of the year, making the possibility to taper oral steroid doses. CONCLUSION: About one-third of the previously AZA- intolerant patients showed adverse effects on taking 6MP. In our series, 20 patients tolerated 6MP, but it was ineffective in 8 CD cases, and valuable mainly in ulcerative colitis patients.
文摘Although systemic steroids are highly efficacious in ulcerative colitis (UC), failure to respond to steroids still poses an important challenge to the surgeon and physician alike. Even if the life time risk of a fulminant UC flare is only 20%, this condition is potentially life threatening and should be managed in hospital. If patients fail 3 to 5 d of intravenous corticosteroids and optimal supportive care, they should be considered for any of three options: intravenous cyclosporine (2 mg/kg for 7 d, and serum level controlled), infliximab (5 mg/kg Ⅳ, 0-2-6 wk) or total colectomy. The choice between these three options is a medical- surgical decision based on clinical signs, radiological and endoscopic findings and blood analysis (CRP, serum albumin). Between 65 and 85% of patients will initially respond to cyclosporine and avoid colectomy on the short term. Over 5 years only 50% of initial responders avoid colectomy and outcomes are better in patients naive to azathioprine (bridging strategy). The data on infliximab as a medical rescue in fulminant colitis are more limited although the efficacy of this anti tumor necrosis factor (TNF) monoclonal antibody has been demonstrated in a controlled trial. Controlled data on the comparative efficacy of cyclosporine and infliximab are not available at this moment. Both drugs are immunosuppressants and are used in combination with steroids and azathioprine, which infers a risk of serious, even fatal, opportunistic infections. Therefore, patients not responding to these agents within 5-7 d should be considered for colectomy and responders should be closely monitored for infections.
文摘The early hypersensitivity reaction and late bone marrow depression are well-known side-effects of azathioprine, whereas interstitial pneumonia is a rare complication. A 40-year old male patient had been treated with azathioprine in consequence of extensive ulcerative colitis for 10 years. He then complained of 7 d of fever, cough and catarrhal signs, without symptoms of active colitis. Opportunistic infections were ruled out. The chest X-ray, CT and lung biopsy demonstrated the presence of interstitial inflammation. Azathioprine therapy was discontinued as a potential source of the pulmonary infiltrate. In response to steroid therapy, and intensive care, the pulmonary infiltrate gradually decreased within 4 wk. Three months later, his ulcerative colitis relapsed, and ileo-anal pouch surgery was performed. In cases of atypical pneumonia, without a proven infection, azathioprine-associated interstitial pneumonitis may be present, which heals after withdrawal of the drug.
文摘AIM: To evaluate the role of azathioprine (AZA) in Indian patients with ulcerative colitis over longer duration of time. METHODS: One hundred f ifty 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?ve patients with severe disease; and (3) combination therapy (AZA + sulfasalazine or 5-aminosalicylates) for na?ve patients with severe disease. The data included patient and disease demographics, effi cacy and toxicity profi le 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 hastherapeutic benefi ts 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.
文摘Azathioprine is currently the key drug in the maintenance treatment of inflammatory bowel diseases. However, there are still some practical issues to be resolved: one is how long we must maintain the drug. Given that inflammatory bowel diseases are to date chronic, non-curable conditions, treatment should be indefinite and only the loss of efficacy or the appearance of serious side effects may cause withdrawal. As regards to efficacy and their maintenance over time, evidence supports the continuous usefulness of the drug in the long term: in fact its withdrawal very substantially increases the risk of relapse. About side effects, azathioprine is a relatively well tolerated drug and even indefinite use seems safe. The main theoretical risks of prolonged use would be the myelotoxicity, hepatotoxicity, and the development of cancer. In fact, serious bone marrow suppression or serious liver damage are uncommon, and can be minimized with proper use of the drug. Recent metanalysis suggests that the risk of lymphoma is real, but the individual risk is rather low, and decision analysis suggests a favorable benefit/risk ratio in the long term. Therefore, in patients with inflammatory bowel diseases in whom azathioprine is effective and well tolerated, the drug should not be stopped. This recommendation concerns the use of azathioprine as a single maintenance drug, and is not necessarily applicable to patients receiving concomitant biological therapy.
文摘Background: Autoimmune hepatitis (AIH) is an immune mediated chronic liver diseasewith a prevalence of 17 cases/100,000. Resistance to the standard treatment of AIH (prednisone and azathioprine) occurs in 15%to 20%. There is currently no standard treatment of patients with steroid refractory AIH. Goals: Determine the efficacy of tacrolimus in the treatment of steroid refractory AIH. Methods: This is a retrospective study evaluating the efficacy of Tacrolimus in the treatment of steroid refractory AIH. Results: Between October 1998 and February 2002, 11 patients with steroid refractory AIH were treated with tacrolimus. Mean age was 63 years. Median duration of steroid treatment before starting tacrolimus was 9 months. Median duration of tacrolimus treatment was 25 months. Median follow up period was 16 months. Median baseline ALT, AST were 77 U/L and 68 U/L and became 21 U/L and 32 U/L respectively at end of follow up (P = 0.005 and 0.01 respectively). Significant weight reduction was seen in all patients (P = 0.02). Tacrolimus treatment was safe and well tolerated. Conclusion: Use of low dose tacrolimus led to successful biochemical and histologic remission and weaning off prednisone in patients with steroid refractory AIH. This data supports further studies in evaluating the use of tacrolimus in the treatment of AIH.
文摘A 55-year-old White woman was first seen in July 1995 with ulceration of the oral mucosa, including the gingiva, labial mucosa, gums, palate and tongue, as well as erosions and blisters on the trunk. A biopsy showed a suprabasal blister with acantholysis. Direct immunofluorescence was positive for intercellular deposits of IgG and C3, and indirect immunofluorescence was positive for intercellular antibodies at a titer of 160. The patient was diagnosed as having pemphigus vulgaris and treated with prednisone 1-1.5 mg/kg/day from 1995 until 1998, but no response was observed (the disease continued to be active with the formation of new lesions. The patent develoyd a number of steroid-complications including diabetes, osteoporosis, Cushing syndrome, hypertension and high-output cardiac failure, and required repeated hospitalization. In August 1998 she was started on azathioprine 100-150 mg/day and continued on prednisone 1 mg/kg/day. One year later, in August 1999, the disease was still active with new lesion formation and persistent oral erosions and dysphagia, despite persistent therapywith azathioprine 150 mg/day and prednisone 1mg/kg/day. Because of the disease severity and the lack of a reponse to treatment, in October 1999 the patient was started on thalidomide therapy 100 mg/day (1.7 mg/kg/day) and continued the prednisone treatment at 1 mg/kg /day together with azathioprine 150 mg/day (2.7 mg/kg/day). There was a good response, with clearing of all oral lesions in 20 days. The prednisone dose was gradually reduced and was discontinued in May 2000; azathioprine was gradually reduced to 50 mg 3 times/week (0.35 mg/kg/day). Thalidomide was continued at a dose of 100 mg/day. The patient was in total clinical remission, being free of both old and new lesions, for the next 14 months, when the thalidomide treatmentwas discontinued as a result of side-effects, including weakness in the legs and paresthesis of the fingers. After the discontinuance of treatment with thalidomide, severe lesions returned. Thalidomide was reintroduced, at 100 mg/day. After 2 months the patient entered total clinical remission and on the last occasion on which she was seen, in May 2003, was found to have remained clear of lesions. The patient continues to take thalidomide at 100 mg/day.
