Impact of Helicobacter pylori infection and mucosal atrophy on gastric lesions in patients with familial adenomatous polyposis

BACKGROUND: There are limited data on factors predicting response to azathioprine and uncertainty regarding the optimal duration of treatment. PATIENTS AND METHODS: The notes of patients attending the Oxford IBD clinic from 1968 to 1999 were reviewed. Remission was defined as no need for oral steroids for at least three months and relapse was defined as active disease requiring steroids. RESULTS: A total of 622 of 2205 patients were treated with azathioprine (272 Crohn's disease, 346 ulcerative colitis, and four indeterminate colitis). Mean duration of the initial course of treatment was 634 days. The overall remission rates were 45% for Crohn's disease and 58% for ulcerative colitis. For the 424 patients who received more than six months of treatment, remission rates were 64% and 87%, respectively. Factors favouring remission were ulcerative colitis (p=0.0001), lower white blood cell (WBC) or neutrophil count (p=0.0001), higher mean cell volume (p=0.0001), and older age (p=0.05). For Crohn's disease, colonic disease favoured remission (p=0.03). Factors that were not significant were age, sex, lymphocyte count, and dose (mg/kg). The proportion of patients remaining in remission at one, three, and five years was 0.95, 0.69, and 0.55, respectively. The chance of remaining in remission was higher if WBC was less than 5 x 10(9) (p=0.03) and in male patients (p=0.01; Crohn's disease only). There was no difference in relapse rates between Crohn's disease and ulcerative colitis. After stopping azathioprine, the proportion of patients remaining in remission at one, three, and five years was 0.63, 0.44, and 0.35 (222 patients). Duration of azathioprine treatment did not affect the relapse rate after stopping treatment (p=0.68). CONCLUSIONS: Azathioprine is effective treatment for ulcerative colitis and Crohn's disease. The efficacy of azathioprine is reasonably well sustained over five years.     

Bone density improves with disease remission in patients with inflammatory bowel disease

BACKGROUND AND AIMS: Patients with inflammatory bowel disease (IBD) are at risk of low bone mineral density (BMD). The aim of this cross-sectional study was to investigate (i) whether patients with IBD in long-term remission have greater bone density relative to patients with active disease, (ii) the effect of remission on BMD in ulcerative colitis and Crohn's disease, and (iii) the effect of azathioprine treatment, used to induce remission, on BMD. PATIENTS AND METHODS: BMD relative to the age-standardised mean (Z-score) was measured by dual-energy X-ray absorptiometry at the left femoral neck and lumbar spine in consecutive patients with IBD. Patients were divided into the following groups: (i) active disease, (ii) remission of less than one year, (iii) remission of one to three years, and (iv) remission of more than three years. Active disease was defined as three or more bowel motions per day, treatment with oral or rectal corticosteroids, and/or presence of a fistula. The subgroups with ulcerative colitis and Crohn's disease and the effect of taking azathioprine were compared. All results were controlled for confounding variables.RESULTS A total of 137 (64 ulcerative colitis, 73 Crohn's disease) patients were evaluated. Patients in remission for more than three years had a normal mean Z-score that was significantly higher than those with active disease at both the femoral neck and the lumbar spine for both ulcerative colitis and Crohn's disease. Patients taking azathioprine and in remission had significantly higher mean Z-scores at the lumbar spine than patients with active disease and who were not taking azathioprine. CONCLUSION: In patients with ulcerative colitis and Crohn's disease, age-matched BMD is higher with increasing duration of disease remission and induction of remission by azathioprine.     

Effective maintenance of inflammatory bowel disease remission by azathioprine does not require concurrent 5-aminosalicylate therapy.

OBJECTIVES: To assess the effect of 5-aminosalicylate treatment in conjunction with azathioprine on remission maintenance in inflammatory bowel disease patients. METHOD: This retrospective study was based on a total of 186 inflammatory bowel disease patients (104 with Crohn's disease; 82 with ulcerative colitis), who were stable on azathioprine for a minimum of 6 months. The median duration of follow-up was 4.3 years (range 0.6-15.5 years). Relapse rates per year of follow-up were compared in an azathioprine + 5-aminosalicylate group (n = 103) and an azathioprine alone group (n = 83); survival curves for cumulative remission rates were compared by log-rank test. Discontinuation of azathioprine in both groups was also recorded, as was the incidence of malignancy. RESULTS: In ulcerative colitis patients (n = 82), mean relapse rates for the azathioprine + 5-aminosalicylate group were 0.21/year compared with 0.19/year for the azathioprine alone group (P = not significant). In Crohn's disease patients (n = 104), mean relapse rates for the azathioprine + 5-aminosalicylate group were 0.27/year compared with 0.3/year for the azathioprine alone group (P = not significant). The cumulative remission percentage (determined from time to first relapse) was used in Kaplan-Meier survival analysis and showed no difference between the azathioprine + 5-aminosalicylate group and the azathioprine alone group by log-rank analysis, for ulcerative colitis and Crohn's disease as well as for all inflammatory bowel disease patients. Concurrent use of 5-aminosalicylates was no more frequent in patients who discontinued azathioprine due to adverse events. The only malignancy recorded was Waldenstr?m's macroglobulinaemia after 7 years of azathioprine therapy. CONCLUSION: Concurrent use of 5-aminosalicylate drugs did not reduce the relapse rates of inflammatory bowel disease patients who were established on azathioprine therapy. The use of 5-aminosalicylate drugs did not lead to any increase in discontinuation of azathioprine due to adverse events.     

Is neutropenia required for effective maintenance of remission during azathioprine therapy in inflammatory bowel disease?

BACKGROUND: Azathioprine is an effective treatment for maintaining remission in inflammatory bowel disease (IBD). It is a matter of debate as to whether neutropenia is required during azathioprine therapy to achieve more effective disease remission. We evaluated whether neutropenia during azathioprine therapy reduced relapse rates in IBD patients. PATIENTS AND METHODS: This retrospective study was based on a total of 173 IBD (96 Crohn's disease (CD), 77 ulcerative colitis (UC)) patients who were stable on azathioprine for a minimum of 6 months. Median duration of follow-up was 4.0 years (range 0.6-21 years). The lowest neutrophil counts during treatment for these patients were recorded. Relapse rates per year of follow-up were compared in non-neutropenic patients (neutrophil count > 2.5 x 10(9), n = 129) and neutropenic patients (neutrophil count < or = 2.5 x 10(9), n = 44) groups, and survival curves for cumulative remission rates compared by log-rank test. RESULTS: Mean relapse rate per year of follow-up for the non-neutropenic group was 0.19/year (SD = 0.37/year) compared with the neutropenic group 0.28/year (SD = 0.43/year) (P = NS). Analysis was performed on UC and CD subgroups, and relapse rates were not significantly different. The cumulative remission per cent determined by Kaplan-Meier survival analysis showed no difference between non-neutropenic and neutropenic groups by log-rank analysis, for UC and CD as well as for all IBD patients. CONCLUSION: Neutropenia < or = 2.5 x 10(9) while on azathioprine does not reduce the relapse rates of IBD patients who were established on azathioprine therapy compared with neutrophil counts > 2.5 x 10(9).     

Compared azathioprine efficacy in ulcerative colitis and in Crohn's disease

AIM: To compare the 6-month efficacy and tolerance of azathioprine in 68 patients with steroid-resistant or steroid-dependent chronic ulcerative colitis (n=30) or Crohn's disease (n=38).METHODS: Clinical remission was defined as a Crohn's Disease Activity Index<150 for Crohn's disease and number of non-bloody stools<=3/day for ulcerative colitis, associated with prednisone requirement<=10 mg/day.RESULTS: Seventy-three per cent of patients with ulcerative colitis had distal or left-sided colitis and 84% of patients with Crohn's disease had pancolitis. Azathioprine was discontinued early for side-effect in 8 (26.7%) patients with ulcerative colitis and in 8 (21.1%) patients with Crohn's disease (NS). In patients treated at least 6 months by azathioprine, clinical remission rates were 77.3% and 70% for chronic ulcerative colitis and Crohn's disease (NS). Complete corticosteroids weaning was obtained significantly more often in ulcerative colitis patients than in Crohn's disease patients (59.1% vs 30%; P<0.05).CONCLUSION: Azathioprine seems to be at least as effective and equally tolerated in steroid-resistant or steroid-dependent chronic ulcerative colitis or Crohn's disease patients.     

A report on efficacy and safety of azathioprine in a group of inflammatory bowel disease patients in northwest Greece

BACKGROUND/AIMS: Inflammatory bowel disease has a variable severity and in a group of patients a second-line treatment with immunosuppressive agents, such as azathioprine is required. The aim of the present study was to determine the efficacy and safety of long-term azathioprine treatment in inflammatory bowel disease patients unresponsive to steroids. METHODOLOGY: We investigated the efficacy of azathioprine in controlling the disease relapse (in combination with other drugs) in 29 patients with inflammatory bowel disease (16 with ulcerative colitis and 13 with Crohn's disease). Patients, who were started on azathioprine in combination with steroids, were those who were resistant to steroids. After controlling the acute phase, steroids were discontinued or reduced in very low doses (up to 4 mg methylprednisone per day) and azathioprine was administered in combination with mesalamine for a period of 12-48 months. RESULTS: Azathioprine (in combination with 5-ASA products and steroids) succeeded in controlling the acute relapse in 24 of 29 patients [82.75%, 15/16 (93.7%) with ulcerative colitis and 9/13 (69.2%) with Crohn's disease]. Of the patients who achieved remission, this was maintained for 1 year at least. Only one case of pancreatitis and one with vomiting and diarrhea were noted a few months after the initiation of therapy and azathioprine was discontinued. CONCLUSIONS: Azathioprine is an effective agent which controls acute relapse of inflammatory bowel disease in many cases in combination with other drugs. Long-term remission can be achieved. Side effects are uncommon.     

Are we giving azathioprine too late？ The case for early immunomodulation in inflammatory bowel disease

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）.     

Pulse cyclophosphamide therapy for inflammatory bowel disease

AIM: To assess the efficacy of intravenous cyclophosphamide pulse therapy for refractory inflammatory bowel disease (IBD).METHODS: We included in our cohort eight patients with (moderate/severe) steroid refractory IBD (4 with ulcerative colitis and 4 with Crohn's disease). They all received 6 cycles of intravenous cyclophosphamide (800mg) per month.RESULTS: Patients entered into remission after the second/third cyclophosphamide pulse. Disease activity decreased. There were no side effects and toxicity. All the patients went into long lasting remission. All Crohn's disease patients and 3 of 4 ulcerative colitis patients achieved complete remission. One patient with ulcerative colitis showed an impressive clinical response but did not enter into remission. For the maintenance, patients with Crohn's disease were treated with methotrexate (15 mg/wk) and patients with ulcerative colitis were treated with azathioprine (2.5 mg/kg body weight/d).CONCLUSION: Remission was maintained in all patients for 6 mo on the average. The drug was well tolerated. These findings suggest that aggressive immunosuppressive therapy may be useful in some refractory patients and further controlled study should be considered in order to fully evaluate this type of treatment as a potential therapy for IBD.     

Pulse cyclophosphamide therapy for inflammatory bowel disease

AIM: To assess the efficacy of intravenous cyclophosphamide pulse therapy for refractory inflammatory bowel disease (IBD). METHODS: We included in our cohort eight patients with (moderate/severe) steroid refractory IBD (4 with ulcerative colitis and 4 with Crohn's disease). They all received 6 cycles of intravenous cyclophosphamide (800 mg) per month. RESULTS: Patients entered into remission after the second/third cyclophosphamide pulse. Disease activity decreased. There were no side effects and toxicity. All the patients went into long lasting remission. All Crohn's disease patients and 3 of 4 ulcerative colitis patients achieved complete remission. One patient with ulcerative colitis showed an impressive clinical response but did not enter into remission. For the maintenance, patients with Crohn's disease were treated with methotrexate (15 mg/wk) and patients with ulcerative colitis were treated with azathioprine (2.5 mg/kg body weight/d). CONCLUSION: Remission was maintained in all patients for 6 mo on the average. The drug was well tolerated. These findings suggest that aggressive immunosuppressive therapy may be useful in some refractory patients and further controlled study should be considered in order to fully evaluate this type of treatment as a potential therapy for IBD.     

Frequency and clinical evolution of indeterminate colitis: a retrospective multi-centre study in northern Italy. GSMII (Gruppo di Studio per le Malattie Infiammatorie Intestinali).

OBJECTIVE: To evaluate the prevalence and the clinical evolution of patients with an initial diagnosis of indeterminate colitis. DESIGN: Retrospective, observational study. SETTING: Fifteen gastrointestinal units in northern Italy. PARTICIPANTS: Patients with an initial diagnosis of indeterminate colitis seen between 1988 and 1993. INTERVENTIONS: Patients were traced through a common database and centres were requested to update their clinical follow-up. MAIN OUTCOME MEASURES: Frequency of patients with an initial diagnosis of indeterminate colitis among those with IBD; rate of patients who subsequently had a definite diagnosis of either Crohn's disease or ulcerative colitis. RESULTS: Fifty out of 1113 IBD patients (4.6%) had been diagnosed as having indeterminate colitis. During follow-up, 37 patients (72.5%) had a definite diagnosis of either Crohn's disease or ulcerative colitis. The cumulative probability of having a definite diagnosis of either ulcerative colitis or Crohn's disease was 80% 8 years after the first one (i.e. the first diagnosis). The probability of having a diagnosis of Crohn's disease was increased in patients with fever at onset, segmental endoscopic lesions or extra-intestinal complications and in current smokers. The probability of having a diagnosis of ulcerative colitis was increased in patients who had not undergone appendectomy before diagnosis. CONCLUSIONS: In our area, indeterminate colitis accounts for about 5% of initial diagnoses of IBD. In about 80% of patients, a diagnosis of either ulcerative colitis or Crohn's disease is made within 8 years. Several clinical and demographic features can help in identifying those patients more likely to have a subsequent diagnosis of Crohn's disease and those more likely to have a subsequent diagnosis of ulcerative colitis.     

Intravenous azathioprine in severe ulcerative colitis: a pilot study

OBJECTIVE: Azathioprine use in acute ulcerative colitis has been limited by its perceived long onset of action. The aim of this study was to determine the safety and clinical effect of an i.v. loading dose of azathioprine in the setting of severe steroid refractory ulcerative colitis. METHODS: Nine hospitalized patients with severe steroid refractory ulcerative colitis were enrolled. Patients 1-3 received 20 mg/kg i.v. azathioprine over 36 h. Patients 4-6 received 40 mg/kg i.v. azathioprine over 36 h. Patients 7-9 received 40 mg/kg i.v. azathioprine as three 8-h infusions over 3 days. Clinical remission was defined as steroid withdrawal and an Ulcerative Colitis Disease Activity Index score of 0. The Inflammatory Bowel Disease Questionnaire was obtained at each visit. White blood cell concentrations and erythrocyte concentrations of 6-thioguanine were obtained. RESULTS: Five of nine patients (56%) had a response and avoided colectomy. Three of nine patients (33%) met the definition for clinical remission. Response was seen within 4 wk. The mean 6-thioguanine concentration for those five patients at 12 wk after infusion was 148.2 pmol/8 x 10(8). Two patients had transient leukopenia and one had transient hepatotoxicity. CONCLUSIONS: Intravenous azathioprine appears to be safe and of clinical benefit in inducing response and avoiding colectomy in severe steroid refractory ulcerative colitis. Data from an i.v. azathioprine trial in Crohn's disease suggests oral dosing alone may obtain the same results. The role of oral dosing alone in severe ulcerative colitis and the role of azathioprine metabolite levels in monitoring efficacy should be investigated further.     

Increased risk for demyelinating diseases in patients with inflammatory bowel disease

BACKGROUND & AIMS: Reports of multiple sclerosis (MS), demyelination, and optic neuritis (ON) associated with anti-tumor necrosis factor alpha therapy resulted in warnings on prescribing instructions for infliximab, etanercept, and adalimumab. However, the underlying relationship between IBD and these neurologic conditions has not been established. METHODS: We performed a retrospective cohort study and a retrospective cross-sectional study using 1988 to 1997 data from the General Practice Research Database. A total of 7988 Crohn's disease and 12,185 ulcerative colitis patients were matched for age, sex, and primary care practice to 80,666 randomly selected controls. In the cohort study, incident cases of MS, demyelination, and/or ON (MS/D/ON) had to occur at least 1 year after registration with the physician and after the diagnosis of IBD. In the cross-sectional study, the diagnosis of MS/D/ON could either precede or follow the IBD diagnosis. RESULTS: In the cohort study, the incidence of MS/D/ON was higher in patients with Crohn's disease and ulcerative colitis compared with their matched controls, reaching statistical significance for ulcerative colitis (ulcerative colitis incidence rate ratio [IRR], 2.63; 95% confidence interval, 1.29-5.15; Crohn's disease IRR, 2.12; 95% confidence interval, .94-4.50). In the cross-sectional study, MS/D/ON was more prevalent in patients with Crohn's disease and ulcerative colitis compared with their matched controls (Crohn's disease odds ratio, 1.54; 95% confidence interval, 1.03-2.32; ulcerative colitis odds ratio, 1.75; 95% confidence interval, 1.28-2.39). CONCLUSIONS: Demyelinating diseases occur more commonly among patients with IBD than among non-IBD patients. Future studies should clarify whether treatment with tumor necrosis factor alpha blockers results in further increased incidence of MS/D/ON among IBD patients.     

The ten-year single-center experience with 6-mercaptopurine in the treatment of inflammatory bowel disease

GOALS: To report the 10-year experience of a single center in treating patients with refractory inflammatory bowel disease (IBD) with relatively lower dose of 6-mercaptopurine (6-MP). STUDY: The charts of 285 patients with IBD (Crohn's disease 160 and ulcerative colitis 125) receiving 6-MP were reviewed. Clinical response, subsequent breakthrough while taking 6-MP, and relapse rates when 6-MP was discontinued and side effects were assessed. RESULTS: Ninety-three percent of the patients were taking 50 to 75 mg/day of 6-MP. Complete remission was achieved in 62%, partial remission in 14.5%, and failure to achieve remission in 23.5% of the patients. Of complete responders, 27.5% had breakthrough while continuing 6-MP. Nine percent of those that achieved a complete remission experienced a relapse after 6-MP was discontinued. Side effects included leukopenia (11.2%), abnormal liver function tests (3.8%), various infections, including pneumonia (3.1%), pancreatitis (2.5%), nausea (2.1%), headache (2.8%), fever (1.4%), hair loss (1%), and rash (0.7%). Two cancers occurred while taking 6-MP: melanoma on the finger and a fatal colonic lymphoma. Four patients continued 6-MP throughout pregnancies and had normal outcomes. CONCLUSIONS: In our experience 6-MP is relatively safe and appears to be as effective at a lower dosage (0.84 mg/kg per day) compared with the recommended higher dosage (1-1.5 mg/kg per day), when leukopenia was more frequent. Serious side effects, although rare, need to be monitored.     

Quality of care for patients with inflammatory bowel disease in East China

AIM： To investigate the quality of care for a hospital based-cohort of patients with inflammatory bowel disease （IBD） from East China according to the current practice guidelines, METHODS： A retrospective review was conducted, involving 177 patients with IBD admitted to Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University between June 2000 and June 2006. Data regarding demographic and clinical characteristics as well as medical therapy including use of oral aminosalisylates, topical therapy, corticosteroid agents, immunomodulatory agents （such as azathioprine） at admission and outpatient clinic visit were analyzed. RESULTS： A total of 177 eligible patients were evaluated in this study, including 71 patients with Crohn＇s disease （CD） and 106 with ulcerative colitis （UC）. All were the Han nationality Chinese with active disease at baseline. All the 106 patients with ulcerative colitis received optimal doses of aminosalisylate while 27 of 68 （39.7%） patients with ileal or colonic CD received the suboptimal doses of aminosalisylate. The incidence of suboptimal dose of aminosalisylate was significantly higher in CD patients with small intestine involvement only （52.8% vs 25.0%, P = 0.019）. Thirty-one （54.4%） patients with active distal or left-sided ulcerative colitis received topical therapy, and 27.8% of patients suffering from severe inflammatory bowel disease did not receive oral or intravenous steroid therapy. Among the 51 patients for whom thiopurine was indicated, only 10 （19.6%） received immunomodulatory agents, and more thanhalf of the 8 patients received a suboptimal dose of azathiopurine with no attempt to increase its dosage. CONCLUSION： The quality of care for IBD patients can be further improved. A suboptimal dose of aminosalicylate is used in treatment of patients with CD, especially in those with small intestine involved only. Topical mesalazine is inadequately used in patients with distal or left-sided colitis. Oral or intravenous steroid therap     

Why children with inflammatory bowel disease are diagnosed at a younger age than their affected parent

BACKGROUND: Genetic anticipation has been proposed to explain observed age differences at diagnosis of Crohn's disease in affected parents and offspring. AIMS: To compare affected parent-child pairs with Crohn's disease and ulcerative colitis with a control group of non-familial patients with inflammatory bowel disease (IBD) in order to quantify whether ascertainment bias could account for this effect. METHODS: 137 affected parent-child pairs from 96 families and 214 patients with sporadic IBD were studied. Age at onset of symptoms and diagnosis were ascertained by interview and disease confirmed from clinical records. RESULTS: Of the 137 affected parent-child pairs, 50 had Crohn's disease only, 51 had ulcerative colitis only, and in 36, one had Crohn's disease and the other ulcerative colitis. The median age of parents at diagnosis was 17.5 years older, 16 years older, and 18 years older in the Crohn's disease, ulcerative colitis, and mixed disease families respectively (p<0.001 in each case). These observed age differences were compatible with those predicted from the regression lines of years of birth against age at diagnosis for the non-familial IBD patients. No evidence was found for an effect of parental sex on age at diagnosis or disease extent in offspring. CONCLUSIONS: There was no evidence of genetic anticipation or genomic imprinting of age at diagnosis in this sample of IBD families. Ascertainment bias is responsible for the age differences at diagnosis between affected parents and children.     

Significance of systemic endotoxaemia in inflammatory bowel disease.

Quantitative and qualitative disturbances in faecal flora suggest a role for enteric bacteria and their products in the pathogenesis of inflammatory bowel disease (IBD). This study investigated the hypothesis that systemically circulating endotoxins are of pathogenic significance in IBD by measuring antibody, cytokine, and acute phase protein responses. Systemic endotoxaemia was found in 88% patients with ulcerative colitis (n = 25) and 94% with Crohn's disease (n = 31) during clinical relapse. Systemic endotoxaemia correlated positively with anatomic extent and clinical activity of ulcerative colitis. Circulating tumour necrosis factor (TNF) was detected in 40% of patients with ulcerative colitis and 45% with Crohn's disease. Plasma TNF concentrations correlated with clinical and laboratory measures of disease activity and were associated with a surgical outcome to the disease episode. Plasma soluble TNF receptor p55 concentration correlated positively with disease activity and endotoxin core antibody concentrations. Plasma IgG endotoxin core antibody concentrations were significantly increased in patients with Crohn's disease and correlated with systemic endotoxaemia. The presence of systemic endotoxaemia, its correlation with disease activity, disease extent, and endotoxin core antibody concentration and the detection of circulating TNF and soluble TNF receptors all support a pathogenic role for endotoxins in IBD.     

Course of disease, drug treatment and health-related quality of life in patients with inflammatory bowel disease 5 years after initial diagnosis

OBJECTIVES: We assessed health-related quality of life (HRQOL) on the basis of a cross-sectional design in a population-based cohort of inflammatory bowel disease patients followed prospectively for 5 years after diagnosis. The aim was to investigate the influence of the course of disease, drug therapy, and relapse pattern on the patients' HRQOL. METHODS: All patients completed the validated Norwegian version of the Inflammatory Bowel Disease Questionnaire (N-IBDQ). We present data from 497 patients, 328 with ulcerative colitis and 169 with Crohn's disease. The mean age was 43.3 years, and 48% were female. RESULTS: Crohn's disease patients treated with systemic steroids or azathioprine had a statistically significant reduction in the N-IBDQ total score compared with non-users. Patients with a more severe disease pattern had a lower N-IBDQ total score. Patients reporting a relapse during the observation period had a significantly lower total score and dimension scores than patients without relapse in both diagnostic groups, and likewise there was a statistically significant decrease in N-IBDQ total score for those with extra-intestinal manifestations compared with those without. A multiple linear regression model showed that the number of relapses during the preceding year in ulcerative colitis, and sex (female gender) in Crohn's disease were the strongest predictor of a reduction in N-IBDQ total score. CONCLUSION: Treatment with systemic steroids or immunosuppressive drugs, a relapsing disease and the presence of extra-intestinal manifestations were associated with a clinically significant reduction in the patients' HRQOL.     

Focally enhanced gastritis in children with Crohn's disease and ulcerative colitis

OBJECTIVES: Focally enhanced gastritis (FEG) has been suggested as a specific diagnostic marker for patients with Crohn's disease. However, the utility of FEG for distinguishing Crohn's disease from ulcerative colitis is uncertain in adults, and the occurrence of this lesion in children has not been defined. The aim of this study was to evaluate the occurrence of FEG and other gastric histological abnormalities in children with inflammatory bowel disease (IBD) and to examine the utility of FEG in discriminating between ulcerative colitis and Crohn's disease. METHODS: This is a retrospective, case-controlled study of upper GI histopathological findings in children with IBD. Gastric histopathology was defined and graded according to the Updated Sydney System. RESULTS: FEG was present in 28 of 43 (65.1%) children with Crohn's disease and five of 24 (20.8%) children with ulcerative colitis, compared to three of 132 (2.3%) children without IBD or one of 39 (2.6%) children with Helicobacter pylori infection. There were no differences between those with and without FEG with regard to upper GI symptoms or previous anti-inflammatory drug ingestion (5-aminosalicylic acid compounds or steroids). All patients with H. pylori infection had chronic antral gastritis, but only one child with H. pylori had FEG. In addition, mild to moderate chronic gastritis was present in 15 of 43 (34.9%) children with Crohn's disease and in 12 of 24 (50%) patients with ulcerative colitis. CONCLUSIONS: The presence of FEG suggests underlying IBD. Although FEG is particularly common in children with Crohn's disease, it does not reliably differentiate between Crohn's disease and ulcerative colitis.     

Inosine triphosphate pyrophosphatase and thiopurine s-methyltransferase genotypes relationship to azathioprine-induced myelosuppression.

BACKGROUND & AIMS: The use of azathioprine (AZA) in inflammatory bowel disease (IBD) patients is limited by toxicity, which occurs in up to 20% of treated patients. Mutations in the thiopurine S-methyltransferase (TPMT) and inosine triphosphate pyrophosphatase (ITPA) genes have been associated with the occurrence of AZA-related toxicity. The aim of our study was to determine the relative contribution of ITPA and TPMT mutations to the development of toxicity induced by AZA treatment in IBD patients. METHODS: ITPA(94C>A, IVS2+21A>C) and TPMT (238G>C, 460G>A, and 719A>G) genotypes were assessed in 262 IBD patients (159 females, 103 males; 67 patients with ulcerative colitis, 195 patients with Crohn's disease) treated with AZA and were correlated with the development of leukopenia and hepatotoxicity. RESULTS: Leukopenia (leukocyte count, <3.0 x 10(9)/L) was observed in 4.6% of treated patients. The frequencies of mutant ITPA 94C>A and TPMT alleles were significantly higher in the leukopenic population compared with patients without leukopenia (16.7% and 5.4%, respectively, for ITPA 94C>A, and 20.8% and 4%, respectively, for TPMT). Moreover, the ITPA 94C>A and TPMT mutations predicted leukopenia: ITPA 94C>A odds ratio, 3.504; 95% confidence interval, 1.119-10.971 (P = .046); TPMT odds ratio, 6.316; 95% confidence interval, 2.141-18.634 (P = .004). Neither TPMT nor ITPA genotype predicted hepatotoxicity. CONCLUSIONS: ITPA 94C>A and TPMT polymorphisms are associated with AZA-related leukopenia in IBD patients.