昆明市炎症性肠病多中心临床资料分析

目的:回顾性调查昆明市近10年炎症性肠病(IBD)患者的发病状况.方法:调查1998年1月-2007年3月七家综合性医院430例住院IBD患者,其中溃疡性结肠炎(UC)379例,克罗恩病(CD)51例.接受结肠镜、组织病理学和钡剂灌肠检查者在UC和CD患者中分别为98.2%和56.2%、2.6%和72.5%、78.4%和31.4%.对IBD患者的年龄、性别、职业、临床表现、内镜和组织病理学检查结果进行分析.结果:UC患者平均年龄为(46.9±15.8)岁,以30～39岁和50～59岁年龄段患者最多,呈双峰状分布;CD患者平均年龄为(41.6±17.2)岁,以20～29岁年龄段患者最多.UC和CD患者均以男性为主,UC患者中脑力劳动者多见.UC患者以腹泻(302,79.7%)、腹痛(285,75.2%)、血便(290,76.5%)为主.CD患者常见腹痛(44,86.3%)、腹泻(28,54.9%)、体重减轻(28,54.9%).UC患者内镜检查、病理检查、钡剂灌肠诊断符合率分别为88.4%(329/372)、24.4%(52/213)、4/10,CD患者分别为86.5%(32/37)、27.5%(11/40)、75%(12/16).UC患者100%为活动期,其中轻、中、重度分别为38.3%、42.2%和19.5%.CD患者活动期占92.2%,缓解期占7.8%,其中轻、中、重度者分别为15.7%、43.1%41.2%.结论:了解10年来昆明市的IBD发病情况及临床特征将有助于临床诊断和治疗.     

Body composition in patients with inflammatory bowel disease: a population-based study

OBJECTIVE: Weight loss and nutritional depletion are common features of inflammatory bowel disease. Our aim was to assess body composition in patients with Crohn's disease (CD) and ulcerative colitis (UC) and to evaluate possible differences between the patient groups and healthy subjects. METHODS: A total of 60 patients with CD, 60 patients with UC, and 60 healthy subjects were investigated. Each group consisted of 24 men and 36 women. Body composition was measured by dual x-ray absorptiometry and Z scores were obtained by comparison to age- and sex-matched normal values. RESULTS: Bone mineral content and lean body mass were significantly lower in patients with CD compared with patients with UC and healthy subjects. The body composition of CD men was more strongly affected than that of women. UC patients had significantly higher fat mass and body mass index than patients with CD and healthy subjects. There was no difference in the percentage of fat mass between the two patient groups. Corticosteroid treatment and smoking had a negative impact on bone mineral content and lean body mass in CD patients independently of each other. CONCLUSIONS: CD was associated with disturbances in body composition: both bone mineral content and lean body mass were significantly reduced, especially in men with CD. Corticosteroid therapy and smoking had a significant influence on body composition in patients with CD. When studying the effects of inflammatory bowel disease on body composition and nutritional status, patients with CD and UC should be evaluated separately.     

Concerns of patients with inflammatory bowel disease: results from a clinical population

OBJECTIVE: The impact of chronic illness is influenced not just by physical symptoms but also by psychosocial factors. The aim of this study was to determine the concerns of inflammatory bowel disease (IBD) patients in a clinical sample, if concerns differ between patients from varied clinical and demographic variables, and if concerns influence well-being beyond the influence of physical symptoms. METHODS: Subjects (n = 259) completed a validated measure of concerns specific to IBD and provided demographic and disease-related information. RESULTS: The most intense concerns involved both physical (e.g., energy level) and psychosocial issues (e.g., achieving full potential). There were numerous differences in disease concerns based on ability to work but none based on disease duration. Factor analysis yielded three indices: body image and interpersonal concerns, general physical impact, and disease stigma. Age and education only affected certain concern indices in subgroups of patients. Greater concerns negatively influenced well-being beyond the influence of physical symptoms. CONCLUSION: Psychosocial factors, in addition to physical symptoms, play an important role on the impact of illness in patients with IBD.     

Effect of oral zinc supplementation on metallothionein and superoxide dismutase concentrations in patients with inflammatory bowel disease

Abstract Oxygen-derived free radicals may contribute to intestinal tissue damage in inflammatory bowel disease. The concentrations of metallothionein and superoxide dismutase, two copper and zinc containing proteins involved in the scavenging of free radicals, were previously found to be decreased in the intestinal mucosa of patients with this disorder. The plasma zinc concentration is often decreased also in these patients. Since zinc is reported to be an efficient inducer of metallothionein synthesis, and probably of superoxide dismutase, we evaluated the effect of oral zinc supplementation on metallothionein and superoxide dismutase levels in patients with inflammatory bowel disease. Fourteen patients with inactive to moderately active inflammatory bowel disease received oral zinc supplementation (300 mg zinc aspartate, equal to 60 mg elemental zinc per day) for 4 weeks in a placebo-controlled double-blind cross-over trial. The plasma zinc concentration of these patients was low at the start of the study (12.2 ± 1.7 μmol/L, P <0.05), when compared to that of 22 healthy controls (13.6 ± 2.3 μmol/L), but increased (P <0.05) towards the levels of controls during the supplementation period (13.3 ± 2.5 μmol/L). The concentrations of metallothionein and superoxide dismutase in plasma and in erythrocytes did not change in relation to the supplementation. The metallothionein concentration in both inflamed and non-inflamed intestinal mucosa was slightly higher after zinc supplementation but the superoxide dismutase concentration in the tissue was not altered. The histological inflammation score of intestinal biopsies, plasma albumin levels, and the disease activity index of the patients did not change during the study. Thus, although zinc supplementation therapy increased plasma zinc concentrations, there was no effect on the plasma, erythrocyte and mucosal metalloprotein levels in inactive to moderately active patients with inflammatory bowel disease.     

Diminished efficacy of colonic adaptation to lactulose occurs in patients with inflammatory bowel disease in remission

Lactulose has been proposed to be beneficial in treating inflammatory bowel disease (IBD). The hypothesis is based on the prebiotic potential of lactulose. A practical approach to testing its usefulness is to determine colonic adaptation to tolerable doses in patients with IBD. Our objective was to determine if a 3-week course of lactulose will decrease BH₂ and symptoms in response to an acute lactulose challenge test in control subjects and IBD patients. The design was a Prospective cohort study. Subjects were given a 30-g lactulose challenge test (test 1), and then ingested 10 g of lactulose twice a day for 3 weeks before being retested (Test 2). A third test was given after a further 5-week washout period. The main outcomes were the change in 4-hr sum of BH₂ (4HrBH₂) values obtained every 30 min, peak BH₂, and 4-hr sum of symptom score (4HrSS) during the lactulose challenge test. In addition, we also report the change in self-reported symptoms and diarrhea during the 3-week administration of lactulose. In controls, 4HrBH₂ decreased from test 1 (380.5 ± 56.6 ppm) to test 2 (288.6 ± 57.4 ppm) (P < 0.05), and returned toward test 1 levels by test 3 (307.5 ± 53.1, P > 0.5). Unlike controls, the 4HrBH₂ in patients failed to achieve significance between test 1 (444.5 ± 55.8 ppm), test 2 (366.5 ± 80.7 ppm, P > 0.2) or test 3 (411.6 ± 62.5 ppm, P > 0.2). 4HrSS results in controls followed a pattern similar to 4HrBH₂, achieving significance only in test 2 (P < 0.02). Symptoms during the intertest periods decreased by the third week in controls (P < 0.05), but not in patients (P > 0.5). Symptoms were lower in patients and varied insignificantly both in challenges and intertest periods. In conclusion, although controls adapt to a 3-week period of lactulose ingestion, IBD patients fail to meet the criteria for adaptation. However, longer studies may be needed to establish whether IBD patients are slower to adapt.     

Effectiveness of darbepoetin-alfa in combination with intravenous iron sucrose in patients with inflammatory bowel disease and refractory anaemia: a pilot study

BACKGROUND: The combination of intravenous iron and recombinant human erythropoietin has been proved to be effective in the treatment of refractory anaemia in patients with inflammatory bowel disease (IBD). Darbepoetin-alpha (DPO) has a three-fold longer terminal half-life than erythropoietin. The purpose of this pilot study was to determine whether darbepoetin-alpha is also effective for the treatment of refractory anaemia in IBD. METHODS: Twenty IBD patients (nine ulcerative colitis and 11 Crohn's disease) and refractory anaemia received intravenous iron sucrose (total iron dose 1.3+/-0.5 g, range 0.7-1.9) and darbepoetin-alfa at the single, weekly dose of 0.9 microg/kg subcutaneously for 4 weeks. Serum erythropoietin, ferritin, transferrin, soluble transferrin receptor, C-reactive protein and interleukin-6 were measured at baseline and after treatment. RESULTS: Haematopoietic response (increase of haemoglobin > or = 2.0 g/dl) was observed in 15 out of the 20 patients (75%). The mean haemoglobin concentrations increased from 9.48+/-0.82 g/dl at baseline to 12.71+/-1.12 g/dl after treatment (P<0.0001). Mean corpuscular volume and serum ferritin levels were also significantly increased whereas mean C-reactive protein levels and endogenous erythropoietin levels significantly decreased after treatment. CONCLUSIONS: In IBD patients with refractory anaemia the administration of darbepoetin in combination with intravenous iron sucrose can raise haemoglobin levels.     

Randomized clinical trial: a pilot study comparing efficacy of low-dose azathioprine and allopurinol to azathioprine on clinical outcomes in inflammatory bowel disease

Background: Treating inflammatory bowel diseases (IBD) using thiopurines is effective; however, a high rate of adverse effects and lack of efficacy limit its use. Retrospective studies have suggested that treatment with low-dose thiopurines in combination with allopurinol is associated with higher remission rates and lower incidence of adverse events.

Aim: To compare the rates of clinical remission and the rates of adverse events in IBD patients treated with either standard treatment with azathioprine or low-dose azathioprine in combination with allopurinol.

Methods: A prospective, open-label study, randomizing thiopurine-naïve IBD patients with normal thiopurine methyltransferase to 24 weeks of treatment with either standard azathioprine dose or low-dose azathioprine and allopurinol.

Results: A total of 46 patients with ulcerative colitis or Crohn’s disease were randomized. We conducted an intention to treat analysis and found a significant (69.6%) proportion of the patients treated with low-dose azathioprine in combination with allopurinol was in clinical remission without the need for steroid or biologic treatment at week 24 compared to 34.7% of the patients treated with azathioprine monotherapy (RR, 2.10 [95% CI: 1.07–4.11]). In the azathioprine group, 47.8% of the patients compared to 30.4% of the patients in the azathioprine–allopurinol group had to withdraw from the study due to adverse events (RR, 1.47 [95% CI: 0.76–2.85])

Conclusions: This study indicated that by changing the treatment strategy from standard weight-based dosing of azathioprine to weight-based low-dose azathioprine in combination with allopurinol, we can increase remission rates in patients with IBD.     

Growth hormone has anabolic effects in glucocorticosteroid-dependent children with inflammatory bowel disease: a pilot study.

The present studies were designed to determine whether recombinant human growth hormone (rhGH) can counteract some of the catabolic effects of glucocorticosteroid therapy in children chronically treated with glucocorticosteroids. Whether rhGH can safely improve short-term linear growth was also investigated. The effect of rhGH on disease activity was also assessed. Ten children (6 boys, 4 girls) with inflammatory bowel disease (IBD) on oral prednisone for at least 4 months prior to these studies were recruited (mean +/- SE, 11.9 +/- 0.9 years). Leucine and glucose isotope studies, body composition, substrate oxidation and energy expenditure rates, and growth factors were measured at baseline (D1) and at 4 months after treatment with rhGH (0.05 mg/ kg. d subcutaneously [SC]) while continuing oral prednisone. Dual-emission x-ray absorptiometry (DEXA) and calcium kinetic analysis ((42)Ca/(46)Ca) were performed also. rhGH was continued for 6 months to assess linear growth in all 10 subjects, 7 of whom continued rhGH for 12 months. Body composition changed favorably with increased fat free mass (+3 kg, P =.001) and decreased percent fat mass (-3.5%, P =.001) after 4 months of treatment. Rates of whole body protein turnover, oxidation, and synthesis remained invariant, with no changes in substrate oxidation or resting energy expenditure rates. Linear growth velocity increased from 3.5 +/- 0.4 cm/yr when the patients were treated with prednisone only, to 7.7 +/- 0.9 after 6 months of combined prednisone/rhGH (P =.001). The growth velocity was sustained in the 7 patients treated with rhGH for 12 months. Plasma insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) concentrations also increased significantly while on rhGH treatment. No changes in calcium absorption were observed but there was a significant increase in kinetic rates of bone calcium accretion (P =.045) as well as in bone-specific alkaline phosphatase concentrations, a measure of bone formation (P =.03). Fasting and 2-hour postprandial glucose concentrations, fasting insulin levels, and HbA(1C) were invariant during combined rhGH/prednisone treatment. The Crohn's disease activity score was unchanged with rhGH therapy. In summary, rhGH treatment of corticosteroid-dependent patients with IBD was associated with positive changes in body composition, bone metabolism, and linear growth, without deterioration of carbohydrate tolerance or intermediate metabolism of substrates. We conclude that treatment with rhGH has beneficial effects in prednisone-dependent growing children. Larger studies will be needed to assess the long-term safety and efficacy of this approach.     

Immunoglobulin containing cells in inflammatory bowel disease of the colon: a morphometric and immunohistochemical study.

Immunoglobulin containing cells in rectal and sigmoid colonic mucosa in endoscopically obtained biopsies from 10 patients with ulcerative colitis and 10 patients with Crohn's disease were studied, using an indirect immunoperoxidase technique. These findings were compared with the immunoglobulin containing cell number in colonic biopsies from 10 control patients with no evidence of colitis. In biopsies from the 20 patients with inflammatory bowel disease a marked increase in area of the lamina propria per millimetre mucosa length was found. In ulcerative colitis a marked increase in number of IgG containing cells was observed. In Crohn's disease the increase in IgG containing cell number is dependent on the degree of activity of inflammation. In quiescent of active Crohn's disease of the colon we found a significant increase of the IgM containing cells. The number of IgM containing cells per millimetre mucosa length will differentiate the pathology of Crohn's disease from ulcerative colitis.     

Clostridium difficile infection in patients with inflammatory bowel disease: a case control study

Objective: Characterization of predisposing factors for Clostridium difficile infection recurrence (rCDI) and outcome in inflammatory bowel disease (IBD) patients.

Methods: Clinical characteristics of 167 inflammatory bowel disease patients with Clostridium difficile infection (IBD-CDI cohort) treated in Helsinki University Central Hospital were gathered. Medical history of the last three months preceding a toxin positive CDI test was recorded. Parameters, including ribotype of C. difficile, mortality and recurrence were compared with age and gender-matched C. difficile patients (CDI cohort).

Results: No difference was found in rCDI between IBD-CDI and CDI cohorts. As compared with IBD subtypes, rCDI was least common among patients with Crohn’s disease. The use of immunosuppressant therapy was higher in IBD patients with two or more CDI episodes. C. difficile ribotype 027 increased the rates for rCDI in IBD patients but not in non-IBD-CDI patients. The prevalence of 027 ribotype and mortality rates did not differ significantly among the cohorts. None of the IBD patients underwent colectomy upon CDI.

Conclusion: IBD patients are not more susceptible for rCDI than non-IBD patients. Predisposing factors for rCDI among IBD patients are associated with immunosuppressant treatments, colon affecting IBD and CDI caused by ribotype 027. CDI does not worsen the prognosis of IBD patients.     

炎症性肠病患者妊娠期管理:一项小规模病例对照研究

目的比较是否行妊娠期管理的炎症性肠病(inflammatory bowel disease,IBD)患者在IBD病情和治疗、妊娠期营养状况和妊娠结局方面的影响。方法纳入我院2008年1月至2014年12月未行妊娠期管理的7例IBD患者,以及2015年1月至2017年10月我院由消化内科、妇产科和营养科医师联合进行妊娠期管理的6例IBD患者,分析比较两组患者的IBD病情和治疗、妊娠期营养指标和妊娠结局。结果与未行妊娠期管理IBD患者比较,进行妊娠期管理的IBD患者具有更长的病程[(124.00±54.02)月vs(48.43±55.43)月,P=0.03],IBD病情缓解期受孕为主(83.3%vs 0,P=0.02),妊娠期IBD病情控制满意,正常的血红蛋白[(119.75±6.12)g/L vs(86.5±14.77)g/L,P<0.001]和血清白蛋白[(36.83±3.22)g/L vs(30.71±2.61)g/L,P=0.003]水平,以及更高的母乳喂养率(83.3%vs 14.3%,P=0.03)。结论由消化科、妇产科、营养科共同对IBD患者进行妊娠期管理,对于选择合适的受孕时机,维持IBD病情缓解和获得良好的妊娠结局至关重要。     

Psychotherapy with chronic inflammatory bowel disease patients: a review

Two distinct factors have lead in the past to the development of several psychotherapeutic treatments for patients with inflammatory bowel diseases (IBD). First, clinicians and researchers believe that psychologic and somatic factors in chronic IBD, Crohn's disease, and ulcerative colitis) are connected. In addition, IBD reduces the health-related quality of life for these patients. The purpose of the psychotherapies is to influence the somatic course of the disease, the psychological state of the patients, or the patients' health related quality of life. This report evaluates the existing studies with regard to the effectiveness of psychotherapy IBD patients received in addition to medical treatment. We have identified 10 psychotherapy studies and 4 additional studies on self management and patient education on this topic. The studies significantly differ from each other in regard to psychotherapeutic methods, inclusion criteria, and outcome assessments. The results so far lead to the conclusion that psychotherapy does not have an impact on the course of the disease but, in some cases, positively influences the patient's psychologic state (such as depression, anxiety, and health related quality of life or coping with the disease). Thus, psychotherapy cannot, in general, be recommended for all patients with chronic IBD. Patients, however, that display a tendency toward psychologic problems, especially as it pertains to their illness, might profit from it.     

Thiopurine-induced myelotoxicity in patients with inflammatory bowel disease: a review

AIM: Probably, the most important and potentially lethal adverse event of azathioprine (AZA) and mercaptopurine (MP) is myelosuppression. Our aim was to conduct a review of AZA/MP-induced myelotoxicity in inflammatory bowel disease (IBD) patients.
METHODS: Bibliographical searches were performed in MEDLINE/EMBASE. The studies evaluating thiopurine-induced myelotoxicity in patients with IBD were reviewed. The cumulative incidence and the incidence rate of AZA/MP-induced myelotoxicity were calculated by a meta-analysis.
RESULTS: In total, 66 studies (8,302 patients) were included. The cumulative incidence of AZA/MP-induced myelotoxicity was 7% (95% confidence interval [CI] 6–8%). The incidence rate (per patient and year of treatment) of the drug-induced myelotoxicity was 3% (95% CI 3–4%). The risk was roughly similar with AZA and with MP (7% vs 9%). The duration of AZA/MP treatment in patients with myelotoxicity ranged from 12 days to 27 yr. The cumulative incidence of infections among AZA/MP-induced myelotoxicity patients was 6.5%. The cumulative incidence of severe myelotoxicity was 1.1% (incidence rate 0.9%). Three deaths were reported due to myelotoxicity (cumulative incidence 0.06%, 95% CI 0.02–0.17%). The risk of death among patients who developed myelotoxicity was 0.94% (95% CI 0.32–2.70%).
CONCLUSION: The incidence rate of myelotoxicity in IBD patients receiving AZA/MP is approximately 3% per patient and year of treatment. Although bone marrow toxicity may develop at any time after starting the therapy, this happens more frequently during the first months. The incidence rate of severe myelotoxicity is less than 1% per patient and year of treatment, and the mortality risk is less than 0.1% (which means that the risk of death among IBD patients who develop myelotoxicity is approximately 1%).