炎症性肠病的临床资料分析及硫唑嘌呤的治疗研究

发布时间：2018-03-19 10:18

本文选题：炎症性肠病　切入点：溃疡性结肠炎　出处：《昆明医科大学》2014年硕士论文　论文类型：学位论文

【摘要】：第一部分：489例炎症性肠病患者临床特点的研究——基于医院的回顾性研究目的分析近10年我院住住院的IBD患者包括UC和CD患者的临床资料,了解我院10年内IBD的临床流行病学特征变化趋势,指导临床诊治。方法选取2004-2013年在昆明医科大学第一附属医院住院的确诊IBD患者作为研究对象,统计分析患者的一般信息(性别、年龄等)、病程、临床类型、分期、分度、结肠镜检查、癌变情况、病理资料以及治疗情况(治疗的主要药物、用药途径)、肠外表现和并发症,回顾分析这些患者的临床特点和诊治现状；按照入院时间将IBD患者A、B两组：A组(2004-2008年),B组(2009-2013年)；再将A、B两组按照疾病种类分为4个亚组,1组为UC患者(A1和B1组),2组为CD患者(A2和B2组),对这4组患者的临床特征的变化趋势进行比较分析。结果 1.IBD患者总计489例,男性293例,女性196例,男女比例1.49：1。UC和CD患者分别有425例和64例,其中男性患者250例和43例,女性患者175例和21例,男女比例为1.43：1和2.05：1。UC患者年龄在4-72岁之间,中位年龄44岁,UC患者在30-39岁年龄段最多。CD患者年龄在12-75岁之间,中位年龄38岁,40-49岁年龄段最多。 2.在过去的10年中,A组为65.9478X104,B组为95.3908X10-4,增长了1.45倍。A1组和A2组,UC：CD=10.9：1,平均入院构成比分别为60.7717X104和5.5669X10-4；B1组和B2组,UC:CD=5.65:1,平均入院比分别为95.7717X10-4和14.3934X10-4。CD增长速度较UC快。 3.425例UC中病程在3周至30年之间,平均3.8年；64例CD患者病程在半年至13年之间,平均3.7年。病程均以少于2年最多见。 4.UC患者99.1%处于活动期,仅0.9%处于缓解期；20.2%轻度,41.6%中度,38.2%重度；19.5%直肠型,44.7%左半结肠型,35.8%广泛结肠型；25.9%初发型,74.1%慢性复发型。CD患者98.4%处于活动期,1.6%处于缓解；轻度68.2%,中度30.2%,重度1.6%；狭窄型7.8%,穿通型4.7%,非狭窄非穿通型87.5%；回肠末端型32.8%,结肠型51.6%,回结肠型15.6%,无上消化道型。 5.395例UC患者接受肠镜检查,其中96.2%黏膜充血水肿、92.4%糜烂或溃疡、30.1%脓性渗出、21.3%黏膜颗粒状84例、19.7%假性息肉和黏膜桥、7.8%肠腔狭窄；282例UC患者肠镜或手术后行病理检查,病理可见95.8%有炎性细胞浸润、33.0%有隐窝炎或隐窝脓肿、8.5%肉芽组织增生、4.6%不典型增生,2.1%管状腺瘤或腺瘤样增生。56例CD患者接受结肠镜或胶囊内镜检查,92.9%黏膜充血水肿、85.7%黏膜糜烂或溃疡、14.3%裂隙状溃疡、27.9%炎性假息肉10例、5.4%瘘管3例、12.5%肠腔狭窄或肠管变形、8.9%鹅卵石样改变,未见不典型增生或腺瘤样增生病例：47例患者行病理学检查,97.9%淋巴细胞聚集、29.7%全壁炎、25.5%.非干酪样肉芽肿、29.8%裂隙状溃疡。 6.UC患者中有11.1%出现肠外表现,其中脂肪肝4.23%、胆石症3.53%,关节炎1.9%、0.7%口腔溃疡、0.7%皮疹；3.1%并发症,其中有2.1%管状腺瘤或腺瘤样增生、0.9%消化道大出血。CD患者中有6.3%出现肠外表现,其中4.7%口腔溃疡、1.6%虹膜炎；17.2%出现并发症,9.3%肠管狭窄、4.7%瘘管、1.6%肛周脓肿、1.6%急性穿孔。 7.UC治疗药物以氨基水杨酸制剂为主,部分联合使用糖皮质激素、免疫抑制剂。23.8%单独使用氨基水杨酸制剂全身或局部治疗；58.3%使用氨基水杨酸制剂和激素全身或局部治疗；有16.7%使用免疫制剂治疗。425例UC患者中40.4%临床缓解,59.1%有效,0.5%无效；转外科手术治疗5例,4例病情缓解,1例因感染死亡。 8.CD主要使用氨基水杨酸制剂、糖皮质激素和免疫抑制剂治疗。64例CD患者39.1%临床缓解,59.3%治疗有效,1例因其他原因死亡；有10.9%患者接受手术治疗。 9.A、B组UC患者在性别、年龄有统计学差异(P0.05)；A、B组的病程长短、病情分期、病情程度、病变累及部位、肠外症状及并发症无差异(P0.05)。 10.A、B组CD患者在性别、确诊年龄、平均年龄、疾病行为和并发症有差异(P0.05)；A、B组的病程长短、病情分期、病情程度、病变累及部位和肠外症状无统计学差异(P0.05)。结论 1.IBD住院患者人数逐年增加,入院构成比亦逐渐增加,CD的增长尤为显著。 2.UC和CD患者的中位年龄分别为44岁和38岁,分别以30-39岁和40-49岁年龄段最多见,均晚于西方国家。 3.UC和CD男女患病比例分别为1.43：1和2.05：1,男性明显高于女性。且近5年的IBD男性患者增多明显,女性患者比例相对下降。 4.UC和CD病程均以少于2年的最常见。 5.UC住院患者大多处于活动期,以中重度为主,疾病类型以慢性复发型为主,受累部位左半结肠型所占比例最大；CD住院患者绝大部分患为活动期,以为轻中度为主,受累部位以结肠型居多,疾病行为以非狭窄非穿通型为主。近5年的IBD患者病程长短、病情分期、病情程度、病变累及部位等方面总体上较前无明显变化。UC和CD的肠外表现和并发症总体发生率较低。 6.IBD临床表现多样性,肠镜检查和病理学组织检查是目前确诊的重要手段,本研究中病例中虽暂无癌变病例,但已发现不典型增生和腺瘤样增生病例,需加强其内镜监测,进一步完善随访制度,提高早期癌变的发现率。 7.UC和CD内科药物治疗效果佳,外科手术率较国内外报道低。第二部分：硫唑嘌呤治疗炎症性肠病的研究目的观察我院IBD患者使用AZA的疗效及安全性。方法收集活动性IBD患者,开始予AZA及糖皮质激素治疗,激素撤离后以AZA维持治疗,随访监测第12、24、48、96周的临床疗效,内镜下黏膜愈合程度及不良反应。结果 1.纳入研究的IBD患者共80例,60例UC,20例CD。UC共60例,完成96周随访30例,完成48周随访40例,完成24周随访50例,完成12周随访52例,退出2例(因自行停药退出),12例失访；CD共20例,完成96周随访6例,完成48周随访12例,完成24周18例,完成12周随访12例,失访2例。 2.AZA治疗UC12周、24周、48周、96周的总有效率分别是84.7%、83.3%、80%、86.7%；缓解率分别是11.5%、20.8%、55%、53.4%。AZA治疗满12周30例停用激素,激素撤停率为65.4%。AZA治疗满48周有40例使用AZA,4例复发共4次,复发率为10%；治疗满96周的有30例,12例复发,复发率40%。内镜下的黏膜愈合率用药后48周、96周为70.0%、66.7%。 3.AZA治疗CD12周、24周、48周、96周的有效率分别是80%、88.9%、100%、100%；缓解率70%、77.8%、75%、66.7%。AZA治疗满12周16例停用激素,激素撤停率为88.9%。AZA治疗满48周12例,2例复发,复发率为16.7%；满96周6例,1例复发,复发率为16.7%。用药后48周,有8例肠镜结果显示正常,2例轻度,2例中度,黏膜愈合率为66.7%;用药后96周,有6例肠镜下黏膜正常,黏膜愈合率为100%。 4.UC患者使用AZA治疗12周、24周较用药前ESR、CRP、WBC计数均无统计学意义(P0.05),Truelove和Witts UC分度对比有统计学意义(P0.05)；用药48周后较用药前的ESR、CRP和Sutherland评分、内镜Mayo评分、Truelove和Witts UC分度有统计学意义(P0.05)；用药96周后较用药前Sutherland评分、Truelove和Witts UC分度比较有统计学意义(P0.05)。 5.UC患者使用不同剂量的AZA治疗,2mg/kg组与1mg/kg在WBC、ESR、CRP和Sutherland评分、内镜下黏膜愈合Mayo评分、临床治疗反应对比均无统计学意义(p0.05)。 6.CD患者使用AZA治疗12周后较用药前ESR、CRP、WBC、HCT、Hb、CDAI评分均无统计学意义(P0.05)；用药24周后较用药前ESR、CRP有统计学意义(P0.05), WBC、HCT、Hb、CDAI评分均无统计学意义(P0.05)；用药48周后较用药前ESR, CDAI评分、内镜下严重度分级(CGSCD)有统计学意义(P0.05), CRP、WBC计数、HCT、Hb无统计学意义(P0.05)；比较用药前和用药96周后的ESR、CRP、HCT、Hb、CDAI评分和内镜下严重度分级均有统计学意义(P0.05)。 7.80例IBD患者,总计有26例发生不良反应,其中20例UC,6例CD。2例CD患者因骨髓抑制停药。结论 1.AZA对UC患者的长期维持缓解及激素撤停率有明显效果。 2.1mg/(kg.d)、2mg/(kg.d) AZA治疗UC,疗效并无明显差异。 3.CD患者使用AZA可有效维持撤离激素后的长程缓解,减少复发率、减少激素的用量。 4.AZA能够明显改善UC和CD患者的黏膜愈合程度。 5.AZA用于IBD的不良反应发生率较高,但严重不良反应发生率低。
[Abstract]:The first part: the research on 489 cases of patients with inflammatory bowel disease clinical characteristics: Based on the retrospective study of the hospital
objective
Analysis of the past 10 years in our hospital in hospital patients with IBD including UC and CD in patients with clinical data, to understand the epidemiological and clinical characteristics of trends in our hospital within 10 years of IBD, clinical diagnosis and treatment guidance.
Method
Selected in the First Affiliated Hospital of Kunming Medical University 2004-2013 years diagnosed IBD patients as the research object, statistical analysis of patients with general information (gender, age), duration, clinical type, staging, grading, colonoscopy, cancer, pathological data and treatment (mainly drug treatment, medicine), extra intestinal manifestations retrospective analysis of clinical features and complications, and the diagnosis and treatment of these patients; patients with IBD A according to the time of admission, B two groups: A group (2004-2008), B group (2009-2013 years); then A, B two groups according to the types of diseases were divided into 4 subgroups, 1 patients (UC group A1 and B1 group), 2 patients with CD (A2 group and B2 group), compare the variation trend of the clinical characteristics of these 4 groups of patients.
Result
A total of 489 cases of 1.IBD patients, male 293 cases, female 196 cases, male to female ratio of 1.49:1.UC and CD were 425 cases and 64 cases, including 250 cases of male patients and female patients with 43 cases, 175 cases and 21 cases, male to female ratio of 1.43:1 and 2.05:1.UC in patients aged 4-72 years old, the median age was 44 years. UC patients 30-39 years of age in most.CD patients aged 12-75 years old, the median age was 38 years, 40-49 years of age the most.
2. in the past 10 years, A 65.9478X104 group, B group was 95.3908X10-4, increased 1.45 times in.A1 group and A2 group, UC:CD=10.9:1, 60.7717X104 and 5.5669X10-4 accounted for the average hospitalization; B1 group and B2 group, UC:CD=5.65:1, the average admission ratios were 95.7717X10-4 and 14.3934X10-4.CD grew faster than UC.
In 3.425 cases of UC disease in 3 to 30 years, an average of 3.8 years; 64 cases of CD patients in the first half of the year to 13 years, average 3.7 years. The course in less than 2 years the most.
99.1% 4.UC patients in the active stage, only 0.9% remained in remission; 20.2% mild, 41.6% moderate and 38.2% severe, 19.5%; type 44.7% left colon rectum, colon, 35.8% wide type; early 25.9% hair, 74.1% chronic relapsing.CD patients, 98.4% in the active stage, 1.6% in remission; 68.2% mild, 30.2% moderate and severe. 1.6%; Stenosis type 7.8%, perforating type 4.7%, type 87.5% non penetrating non stenosis; ileal colonic type 51.6%, type 32.8%, type 15.6%, ileocolon, digestive tract.
5.395 cases of UC patients received colonoscopy, 96.2% of which 92.4% mucosal congestion and edema, erosion or ulcer, 30.1% purulent exudation, 21.3% mucosa granular in 84 cases, 19.7% pseudopolyps and mucosal bridge, 7.8% lumen stenosis; 282 cases of UC patients underwent colonoscopy or surgical pathology, pathology showed 95.8% inflammatory cell infiltration, 33% cryptitis or crypt abscess, 8.5% granulation tissue hyperplasia, 4.6% atypical hyperplasia, 2.1% tubular adenoma or adenomatoid hyperplasia of.56 CD patients received colonoscopy and capsule endoscopy, 92.9% mucosal edema, 85.7% mucosa erosion or ulcer, 14.3% fractured ulcer, 10 cases of 27.9% inflammatory pseudopolyps, 3 cases of 5.4% fistula. 12.5% lumen stenosis or bowel deformation, 8.9% cobblestone like change, no dysplasia or adenomatous hyperplasia cases: 47 cases of patients with pathological examination, 97.9% lymphocyte aggregation, 29.7% wall inflammation, 25.5. Non caseous granuloma, 29.8% crack Lyriform ulcer.
With 6.UC there were 11.1% extra intestinal manifestations, including fatty liver 4.23%, 3.53% cholelithiasis, arthritis 1.9%, 0.7% oral ulcers, 0.7% rash; 3.1% complications, including 2.1% tubular adenoma or adenomatous hyperplasia, 0.9% gastrointestinal bleeding in patients with.CD 6.3% had extra intestinal manifestations, including 4.7% oral ulcers, 1.6% iritis; 17.2% had complications, 9.3% stricture, 4.7% fistula, 1.6% perianal abscess, acute perforation in 1.6%.
7.UC therapeutics to aminosalicylates, part of the joint use of corticosteroids and immunosuppressive agents used alone.23.8% aminosalicylates systemic or topical therapy; 58.3% amino acid preparations and hormone systemic or local therapy; 16.7% of the use of immune agents for the treatment of.425 patients with UC in remission, 40.4% clinical and 59.1% effective, 0.5% ineffective; surgical surgical treatment of 5 cases, 4 cases of remission, 1 cases died of infection.
8.CD the main use of aminosalicylates, alleviate the glucocorticoid and immunosuppressive treatment of.64 patients with CD 39.1% clinical, 59.3% effective treatment, 1 cases of death due to other reasons; 10.9% patients received surgical treatment.
9.A, B group of UC patients in gender, age had significant difference (P0.05); A B group, the duration of disease, disease stage, severity of disease, lesion site, no difference in extraintestinal symptoms and complications (P0.05).
10.A, B group of CD patients in gender, age of diagnosis, average age, illness behavior and complications difference (P0.05); A B group, the duration of disease, disease stage, severity of disease, no significant difference between the involved area and extraintestinal symptoms (P0.05).
conclusion
The number of hospitalized patients with 1.IBD increased year by year, admission proportion has increased gradually, CD growth is particularly significant.
The median age of 2.UC and CD were respectively 44 and 38, respectively in 30-39 and 40-49 years old age the most common than western countries.
3.UC and CD of male and female prevalence ratio were 1.43:1 and 2.05:1, the male was higher than female. Male IBD patients and nearly 5 years increased significantly, the proportion of female patients with relative decline.
4.UC and CD are the most common disease in less than 2 years.
Most of 5.UC patients in the active stage, with moderate to severe disease, type of chronic recurrent type, the affected area of left colon type accounted for the largest proportion of hospitalized patients suffering from CD; most of the active phase and that mild to moderate, the affected area in the colon than that in non stenosis disease behavior nonpenetrated type. For nearly 5 years. The course of disease in patients with IBD disease stage, length, severity, overall extraintestinal manifestations and complications involved area on the whole is no obvious changes of.UC and CD showed a low incidence rate.
6.IBD has a variety of clinical manifestations, histological examination and pathological examination is an important means of diagnosis, patients in this study although no cancer cases, it has been found that the atypical hyperplasia and adenomatous hyperplasia cases, the need to strengthen its endoscopic monitoring, to further improve the follow-up system, improve the detection rate of early cancer.
Therapeutic effect of 7.UC and CD medical, surgical rates reported at home and abroad.
The second part: the study of azathioprine in the treatment of inflammatory bowel disease
objective
To observe the efficacy and safety of IBD patients in our hospital using AZA.
Method
The collection of active IBD patients administered with AZA and glucocorticoid therapy, hormone withdrawal after AZA maintenance treatment, clinical follow-up in 12,24,48,96 weeks, healing of mucosa and adverse reaction under endoscope.
Result
1. patients with IBD, a total of 80 cases, 60 cases of UC, 20 cases of CD.UC total of 60 patients completed 96 weeks of follow-up 30 patients completed 48 weeks of follow-up of 40 cases, 50 cases were followed up for 24 weeks to complete, completed 12 weeks of follow-up of 52 cases, 2 cases of exit (due to stop the drug withdrawal), 12 cases were lost CD; a total of 20 patients completed 96 weeks of follow-up 6 patients completed 48 weeks of follow-up of 12 cases, 18 cases completed 24 weeks, 12 weeks follow-up in 12 cases, 2 cases were lost.
2.AZA for UC12 weeks, 24 weeks, 48 weeks, 96 weeks, the total effective rate is 84.7%, 83.3%, 80%, 86.7%; the remission rate were 11.5%, 20.8%, 55%, 12 weeks of 53.4%.AZA treatment with 30 cases of steroid and steroid withdrawal rate of 65.4%.AZA after 48 week in 40 cases with AZA, 4 cases a total of 4 times of recurrence, the recurrence rate was 10%; for the full 96 weeks of the 30 cases, 12 cases of recurrence, the recurrence rate of 40%. endoscopic mucosal healing rate of 48 weeks after medication for 96 weeks, 70%, 66.7%.
3.AZA for CD12 weeks, 24 weeks, 48 weeks, 96 weeks were 80%, 88.9%, 100%, 100%; 77.8%, response rate was 70%, 75%, 12 weeks of 66.7%.AZA treatment with 16 cases of steroid and steroid withdrawal rate of 88.9%.AZA after 48 weeks in 12 cases, 2 cases of recurrence, the recurrence rate was 16.7%; over 96 weeks in 6 cases, 1 cases of recurrence, the recurrence rate was 48 weeks after 16.7%. treatment, 8 cases showed normal colonoscopy, 2 cases of mild, 2 moderate cases, mucosal healing rate was 66.7%; 96 weeks after treatment, 6 cases of normal mucosa under endoscopy, mucosal healing rate was 100%.
12 weeks of treatment with AZA in patients with 4.UC, 24 weeks after medication, ESR, CRP, WBC were not statistically significant (P0.05), there was statistical significance in Truelove and Witts UC (P0.05); contrast index after 48 weeks of treatment compared with before treatment ESR, CRP and Sutherland score, endoscopic Mayo score was statistically significant, and Truelove the Witts UC index (P0.05); after 96 weeks of treatment compared with before treatment Sutherland score, Truelove and Witts UC index were statistically significant (P0.05).
AZA 5.UC patients treated with different doses of the 2mg/kg group and the 1mg/kg in WBC, ESR, CRP and Sutherland score, Mayo score and endoscopic mucosal healing, clinical effect comparison was not statistically significant (P0.05).
12 weeks of treatment with AZA in patients with 6.CD after ESR compared with before treatment, CRP, WBC, HCT, Hb, CDAI scores were not statistically significant (P0.05); after 24 weeks of treatment compared with before treatment ESR and CRP had statistical significance (P0.05), WBC, HCT, Hb, CDAI scores were not statistically significant (P0.05); after 48 weeks of treatment compared with before treatment ESR, CDAI score, severity of endoscopic (CGSCD) had statistical significance (P0.05), CRP, HCT, WBC count, Hb had no statistical significance (P0.05); compared with before treatment and after 96 weeks of treatment, ESR, CRP, HCT, Hb, CDAI score and endoscopic the severity grading had statistical significance (P0.05).
7.80 cases of IBD patients, a total of 26 cases of adverse reactions, including 20 cases of UC, 6 cases of CD.2 CD patients with bone marrow suppression withdrawal.
conclusion
1.AZA of UC patients to maintain long-term remission and steroid withdrawal rate have obvious effect.
2.1mg/ (kg.d), 2mg/ (kg.d) AZA in the treatment of UC, no significant difference in efficacy.
The use of AZA can effectively maintain the evacuation after long term hormone remission 3.CD patients, reduce the recurrence rate, reduce the amount of hormones.
4.AZA can significantly improve UC and CD patients, healing of mucosa.
5.AZA for the adverse reaction rate of IBD is higher, but the occurrence of severe adverse reaction rate is low.

【学位授予单位】：昆明医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R574

【参考文献】