Drug therapy of chronic inflammatory intestinal diseases--current status of 5-aminosalicylic acid

Assessment of the nature, location and extent of the disease, disease activity and the intestinal and extraintestinal complications and manifestations is an essential prerequisite in the treatment of inflammatory bowel disease. Corticosteroids, sulfasalazine (SASP) and rectal administration of 5-aminosalicylic acid (5-ASA) are effective in the treatment of ulcerative colitis. Oral 5-ASA in the form of a slow-release preparation is probably also effective. Rectal SASP or 5-ASA in addition to corticosteroids is indicated in distal colitis. In severe pancolitis oral or intravenous corticosteroids are required, whilst in less severe forms SASP or 5-ASA can be used. However, the safety of 5-ASA over longer treatment periods has yet to be verified. Surgery is indicated in colitis refractory to maximal treatment over several months. Apart from parenteral or enteral nutrition, treatment with prednisolone is effective in acute exacerbations of Crohn's disease. SASP is possibly effective in colonic disease. The role of 5-ASA has yet to be defined. A prednisolone-induced remission can be maintained by means of low doses of prednisolone. SASP is probably not effective, whilst with 5-ASA conclusive data are missing. Metronidazole and azathioprin are considered to be reserve drugs and can be used in the treatment of fistulae or in order to cut down the dosage of prednisolone during remission. Substitution with vitamins and trace elements is necessary in a large number of patients with Crohn's disease.     

Cardio vascular disease associated with ulcerative colitis

Although cardiovascular complications such as Aortic syndrome (Takayasu's aortitis), Pericarditis and Myopericarditis might not be common, these complications should be noted as one of the fatal manifestation of IBD. It can be the sole or one of the several extraintestinal manifestation of either ulcerative colitis or Crohn's disease. Because of the therapeutic implications, we reviewed the literature documenting cardiovascular complication associated with ulcerative colitis. The comparatively high prevalence of Takayasu's aortitis with ulcerative colitis in Japanese patients may be explained by a immune genetic influence. HLA-B52 and DR2, were highly expressed in the patient with both disease. Myopericarditis and Pleuropericarditis associated with IBD were divided into two groups by pathogenesis, 1) drug (5-ASA)-induced disease, and 2) autoimmune disease. The cardiovascular symptom may occur while the patient's gastrointestinal disease is quiescent.     

溃疡性结肠炎患者肠道菌群与血TNF-α、内毒素水平的关系

目的 探讨溃疡性结肠炎(UC)患者肠道菌群特点及血中肿瘤坏死因子(TNF)-α、内毒素含量变化,为UC治疗和病情评估提供依据.方法 选取确诊的57例UC患者,其中缓解期28例,活动期29例,10例健康体检者作对照.运用可培养细菌菌群分析方法,对每例受试者粪便进行分析;清晨空腹抽血酶联免疫吸附(ELISA) 法测TNF-α含量,采用鲎试剂三肽显色基质偶氮法测内毒素水平.结果 UC活动期组与缓解期组、对照组比较乳酸杆菌数量明显减少,差异显著(P<0.01);双岐菌UC缓解期组数量少于对照组(P<0.05),活动期组数量明显减少,与缓解期组、对照组比较均具有显著性差异(P<0.01);UC活动期组内毒素水平明显升高,与缓解期组、对照组比较均具有显著性差异(P<0.01);UC活动期组TNF-α水平明显升高,与缓解期组、对照组比较均具有显著性差异(P<0.01);乳酸杆菌数量与血桨内毒素水平、血清TNF-α含量均呈负相关(r=-0.860、-1.038,P<0.01);双岐菌数量与血桨内毒素水平、血清TNF-α含量均呈负相关(r=-0.932、-0.843,P<0.01).结论 UC患者存在菌群失调;测定UC患者血TNF-α、内毒素水平有益于评估病情.     

Algorithm of diagnosis and treatment of complicated forms of nonspecific ulcerative colitis and Crohn's disease

AIM: To detect complicated forms of nonspecific ulcerative colitis and Crohn's disease, to calculate treatment algorithm. MATERIAL AND METHODS: The results of a 20-year prospective trial including 313 patients with nonspecific ulcerative colitis (n = 180) and Crohn's disease (n = 133) have been analysed. The following parameters were considered: clinical findings with calculated index of the disease activity, endoscopic, x-ray and morphological data. All the information was processed using computer programs Biostat and Exell 97 Mean and standard deviations were calculated. Chi-square and Fisher's criteria were used. RESULTS: Complicated forms of nonspecific ulcerative colitis and Crohn's disease were detected and characterized. Programs of treatment of complicated forms of intestinal inflammatory diseases and measures for maintenance of the remission are proposed.     

Transrectal ultrasound in the diagnosis and management of inflammatory bowel disease

BACKGROUND AND STUDY AIMS: To aim of the present study was to determine the value of transrectal ultrasonography (TRUS) in the assessment of disease activity in ulcerative colitis patients, and in differentiating between mucosal inflammation and transmural inflammation. PATIENTS AND METHODS: TRUS examinations were used to study 30 control individuals and 76 patients with inflammatory bowel disease, including 50 cases of ulcerative colitis and 26 of Crohn's disease. A rigid linear endorectal probe was used to examine the rectal wall. RESULTS: In the 30 control individuals, the rectal wall showed five layers, with a mean total diameter of 2.6 mm. There were significant differences between patients with quiescent ulcerative colitis, active ulcerative colitis, and control individuals with regard to the total rectal wall thickness (P<0.001), submucosal thickness (P<0.001) and mucosal thickness (P<0.001). Using cut-off values, differentiation between active ulcerative colitis and remission ulcerative colitis was found to be 100% specific and 73 % sensitive for submucosal thicknesses. TRUS revealed a 100% specificity in differentiating between remission ulcerative colitis and control cases based on the total rectal wall thickness, submucosal, and mucosal thicknesses. In the differential diagnosis of active and remission ulcerative colitis, an increase in submucosal wall thickness and the existence of arterial and venous capillary flow in the submucosa were found to be specific and more sensitive than the other parameters. TRUS examination revealed transmural inflammation in 21 of the 26 Crohn's disease patients, and mucosal inflammation in all 50 of the ulcerative colitis patients. CONCLUSION: TRUS is a reliable and easy method of assessing ulcerative colitis activity and differentiating between rectal diseases.     

Small bowel magnetic resonance imaging for inflammatory bowel disease

The presented concept of hydro-magnetic resonance imaging (MRI) using a 2.5% mannitol solution as an orally applicable intraluminal contrast agent is a meaningful, reproducible, and reliable imaging method for the depiction of the small bowel. Especially in patients with Crohn's disease, hydro-MRI is the imaging method of first choice because hydro-MRI offers the advantage of a superior depiction of the inflamed bowel wall and the extramural complications of this disease without radiation exposure. In addition, hydro-MRI allows for a reliable assessment of the inflammatory activity, especially for the differentiation between an active and an inactive (scarred) stenosis. In particular, the mural enhancement, the length as well as the wall thickness of inflamed bowel segments, are considered to be significant MR parameters for the determination of the activity of Crohn's disease. Hydro-MRI of the colon is suitable for the depiction of pathologic changes in ulcerative colitis, but in contrast to Crohn's disease, the assessment of disease activity by hydro-MRI is unreliable in ulcerative colitis, probably because of the low spatial resolution (mucositis in ulcerative colitis vs. transmural inflammation in Crohn's disease). Hydro-MRI does not allow a reliable classification of inflammatory bowel diseases, but in ambiguous cases, hydro-MRI may provide helpful information for the differentiation of Crohn's disease and ulcerative colitis. There are no data of larger patient groups published regarding MR findings in inflammatory bowel diseases besides Crohn's disease and ulcerative colitis, but hydro-MRI is a promising imaging tool for these entities, which should be assessed in additional studies.     

An investigation into the validity of the present classification of inflammatory bowel disease

To assess the validity of the present subdivision of patients with inflammatory bowel disease into those with Crohn's disease of the small bowel or of the colon and those with ulcerative colitis, 252 patients with inflammatory bowel disease have been studied by questionnaire and case note review. One hundred and seventy-two variables concerning the nature and frequency of symptoms in remission and relapse, the incidence of complications and results of investigation have been analysed by computer. As expected, there were many highly significant variables between patients with ulcerative colitis and those with Crohn's disease of the small bowel. The latter showed evidence of a more severe disease course with more complications. There were similar, although less marked, differences between patients with Crohn's disease of the colon and those with Crohn's disease of the small bowel. There were very few differences in disease course between patients with Crohn's disease of the colon and those with ulcerative colitis. The results suggest that while separate classification of patients with Crohn's disease of the small bowel is justified on clinical grounds, the present separation of patients with disease confined to the colon into groups labelled ulcerative colitis or Crohn's disease of the colon is not. Alternative methods of classification should therefore be investigated.     

Long-term prognosis of ulcerative colitis

Despite its intermittent course of activity and remission, the good response to salazopyridine and steroids makes the long-term prognosis of ulcerative colitis favorable. The number of non-active type ulcerative colitis is increasing and consequently, the rate of active disease and relapse is decreasing every year. More than 90% of the patients even with disease of 10 or more years are able to work almost with no limits for the daily living. The colectomy rate in Japan is 4.1% after one year of the onset of the disease and 6.8% after 2 years. Thereafter approximately 1% of the patients undergo surgery yearly. The most common reasons of surgery are complications such as massive bleeding, perforation or toxic megacolon. Other indications are chronic continuous disease and cases with frequent relapses. Considering the extension of the disease, about one-third of the total colitis type and 10% of the left-sided type undergo surgery. The risk of colonic cancer is higher in patients with total colitis type and when has had the disease for more than 10 years. Most of the them are flat type poor-differentiated adenocarcinomas. Therefore patients with total colitis type for more than 10 years should undergo colonoscopic surveillance.     

Ulcerative Colitis: Epidemiology,Diagnosis, and Management

Ulcerative colitis is a chronic idiopathic inflammatory bowel disease characterized by continuous mucosal inflammation that starts in the rectum and extends proximally. Typical presenting symptoms include bloody diarrhea, abdominal pain, urgency, and tenesmus. In some cases, extraintestinal manifestations may be present as well. In the right clinical setting, the diagnosis of ulcerative colitis is based primarily on endoscopy, which typically reveals evidence of continuous colonic inflammation, with confirmatory biopsy specimens having signs of chronic colitis. The goals of therapy are to induce and maintain remission, decrease the risk of complications, and improve quality of life. Treatment is determined on the basis of the severity of symptoms and is classically a step-up approach. 5-Aminosalycilates are the mainstay of treatment for mild to moderate disease. Patients with failed 5-aminosalycilate therapy or who present with more moderate to severe disease are typically treated with corticosteroids followed by transition to a steroid-sparing agent with a thiopurine, anti–tumor necrosis factor agent, or adhesion molecule inhibitor. Despite medical therapies, approximately 15% of patients still require proctocolectomy. In addition, given the potential risks of complications from the disease itself and the medications used to treat the disease, primary care physicians play a key role in optimizing the preventive care to reduce the risk of complications.     

Cyclosporine for severe ulcerative colitis

OBJECTIVE: To evaluate evidence for the use of cyclosporine in treating patients with severe ulcerative colitis. DATA SOURCES: A literature search was performed using MEDLINE, EMBASE, Cochrane Database, and ISI Web of Knowledge (1966-November 2005) with the search terms cyclosporine, cyclosporin A, CsA, ulcerative colitis, UC, inflammatory bowel disease, IBD, steroid-refractory, and immunosuppression. Additional papers were located by hand-searching relevant references. Only human studies in adults and literature published in English were included. DATA SYNTHESIS: Intravenous cyclosporine has been evaluated for the treatment of severe ulcerative colitis in 4 randomized, controlled trials, as well as in many open-label and retrospective studies. Studies that evaluated cyclosporine for severe ulcerative colitis were reviewed. All 4 controlled trials showed an initial positive clinical response as defined by the Crohn's Activity Index when intravenous cyclosporine 4 mg/kg/day was administered as monotherapy or combined with intravenous corticosteroids. One of the 4 trials indicated that high-dose cyclosporine (4 mg/kg/day) has no additional clinical benefit over the low-dose (2 mg/kg/day) and that the lower dose may improve safety related to dose-dependent adverse effects. CONCLUSIONS: There is evidence to support the use of intravenous cyclosporine for patients with severe ulcerative colitis who are refractory to corticosteroid therapy. Because most of the adverse effects associated with cyclosporine are dose dependent, therapy should be initiated with the lower 2 mg/kg/day dose. Subsequent doses should be adjusted based on cyclosporine blood concentrations of 150-250 ng/mL. Cyclosporine should be used only to induce remission and serve as a "bridge" to azathioprine or 6-mercaptopurine maintenance therapy. At this time, there are insufficient data to support the long-term use of cyclosporine monotherapy for avoidance of surgery or maintenance of remission.     

Current status of drug therapy for inflammatory bowel disease

Both topical steroids and sulfasalazine are useful for patients with ulcerative proctitis and distal colitis. For patients with more extensive ulcerative colitis with moderate symptoms, prednisone and/or sulfasalazine will result in improvement in about 80% of patients. Parenteral corticosteroids or ACTH should be used in the setting of severe colitis and antibiotics added if the patient appears toxic. Sulfasalazine is of proven efficacy as maintenance therapy in ulcerative colitis. Prednisone and sulfasalazine are useful in Crohn's disease, although the latter is of limited use in patients with ileitis alone. Immunosuppressive agents such as azathioprine and 6-mercaptopurine may be especially helpful in Crohn's patients refractory to other drugs or dependent on high doses of steroids. Azathioprine is of proven usefulness as maintenance treatment of Crohn's disease. Metronidazole is as effective as sulfasalazine in Crohn's disease involving the colon and has an important role in severe perineal disease. New forms of steroid enemas and topical and oral forms of 5-aminosalicylate based on sulfasalazine should be available soon for patients with both ulcerative colitis and Crohn's disease.     

Management of ulcerative colitis

Ulcerative colitis is a chronic inflammatory bowel disease. The disease is diagnosed on the basis of clinical parameters and endoscopic-histologic evaluation. 5-aminosalicylic acid (5-ASA, mesalamine) represents the first-line treatment of choice. For patients with distal and left-sided disease the use of rectal preparations is effective. Most patients respond to 5-ASA suppositories or to topic steroids such as budesonide suppositories or hydrocortisone foam. For patients with extended disease, oral medications are mandatory. In case of low- to moderate-grade inflammation, 5-ASA preparations should be implemented. In the case of severe disease treatment with steroids is required. Following induction of remission, prophylactic treatment with 5-ASA (1.5 g/d) should be maintained. For patients with frequent or severe relapses, immunosuppressive therapy with azathioprine or 6-mercaptopurine is indicated. In case of a fulminant course of disease, treatment with intravenous cyclosporine is required in patients who have not responded to high-dose intravenous steroids. When all conservative treatment options fail, proctocolectomy with construction of an ileoanal pouch should be performed. New therapeutic strategies such as infliximab and interferons are being evaluated in clinical trials. The long-term complications of ulcerative colitis include steroid-induced osteoporosis and anemia and should be treated adequately. Finally, the risk for development of colorectal cancer increases steadily with disease duration and dysplasia should be screened for by endoscopic surveillance programs.     

"Take your medicine": nonadherence issues in patients with ulcerative colitis.

Ulcerative colitis is a lifelong disease causing inflammation and ulceration of the colon. Symptoms of ulcerative colitis include abdominal pain, bloody diarrhea, bloating, and fecal urgency. The current standard therapy for mild to moderate ulcerative colitis is the use of 5-aminosalicylates, with patients requiring continuous treatment to maintain remission. A substantial proportion of patients, however, are nonadherent to prescribed 5-aminosalicylate treatment regimens, resulting in a greater chance of disease relapse with severe associated symptoms. There are many reasons why a patient with ulcerative colitis may be nonadherent including the patient's perception of the condition or a lack of understanding about the disease or treatment. Multiple daily dosing or rectal administration of 5-aminosalicylate medications also can adversely affect adherence rates. Because gastrointestinal nurses often are the primary points of contact for patients with ulcerative colitis, they are in a unique position to take simple steps that will improve adherence rates and thus increase the efficacy of prescribed therapy. This article highlights important aspects of education and patient care for patients with ulcerative colitis.     

CT小肠造影影像对结肠型克罗恩病与溃疡性结肠炎的诊断价值

目的 探究CT小肠造影（CTE）对结肠型克罗恩病与溃疡性结肠炎的诊断及鉴别诊断价值。方法 选取蚌埠医学院第一附属医院和南京中医药大学附属江苏省中医院于2019年1月～2022年1月收治的结肠型克罗恩病患者36例和溃疡性结肠炎患者36例行CTE检查,分别观察两组影像特征,结合实验室指标、临床表现对克罗恩病和溃疡性结肠炎患者进行回顾性分析。结果36例克罗恩病患者中,CTE影像示肠壁不均匀增厚21例、肠道狭窄22例、瘘管形成7例及累及升结肠21例,均高于溃疡性结肠炎患者,差异有统计学意义（P<0.05）;36例溃疡性结肠炎患者,粘液便18例及血便22例高于克罗恩病患者（P<0.05）,溃疡性结肠炎患者平均发病年龄较结肠型克罗恩病患者平均发病年龄大（P<0.05）。克罗恩病患者与溃疡性结肠炎患者的C反应蛋白及红细胞沉降率含量均值分别为28.17 mg/L vs 17.67 mg/L、32.25 mm/h vs 22.95 mm/h;C反应蛋白及红细胞沉降率含量的平均值对克罗恩病与溃疡性结肠炎的鉴别无统计学意义（P>0.05）。结论 通过CTE影像特征更直观地对结肠型克罗...     

Surgical treatment of ulcerative colitis

Known indications in the surgical treatment of ulcerative colitis are acute severe attacks, intractability, and cancer prophylaxis. This study was performed to determine the optimum timing of operation in ulcerative colitis. Of 59 patients with intractability, 9(15%) had severe attacks and 6(10%) developed colorectal cancer. The mean duration of disease was 3.6 yr for 14 with severe attacks alone, 6 yr for 44 with intractability alone, 8.6 yr for 9 with both, and 16.5 yr for 16 with cancer prophylaxis. In this series, the operations for intractable disease were more likely to be delayed, and the longer these were delayed, the higher the rate was of pre- and postoperative complications.     

溃疡性结肠炎伴不全肠梗阻并严重感染的诊治分析

【目的】探讨溃疡性结肠炎(UC)伴不全肠梗阻并发严重感染的诊治方法。【方法】回顾性分析本院近期收治的一例 UC 伴不全肠梗阻并发严重感染患者的临床资料,三次入住本院消化内科症状无明显改善后转入本科室治疗,拟逐步停用激素及免疫抑制剂后行探查手术,同时予以肠内外营养支持治疗,三个月后行腹腔镜结肠肝曲癌根治+左半结肠切除术。【结果】患者腹泻症状较术前明显缓解,未再诉腹痛、腹胀;体温恢复正常;肛瘘病情好转;术后病检结果为 UC 伴结肠肝曲癌变。【结论】UC 患者在使用激素、抗免疫治疗时出现不全肠梗阻应早期预防性给予抗感染治疗,避免出现爆发感染,疗效不佳时应尽早手术治疗;对于病程长的 UC 患者出现类似克隆恩病肠壁增厚不全肠梗阻时应早期手术,谨防癌变。     

Cytapheresis (CAP) with leukocyte removal filter/bead column as one therapeutic option for inflammatory bowel disease

Inflammatory bowel disease (IBD) like Crohn's disease and ulcerative colitis are chronic inflammatory disorders that affect the bowel. The disease is characterized by periods of clinical remission and relapse due to severe intestinal inflammation. Drug therapy of IBD is associated with unpleasant side effects. Further, efficacies of conventional drugs decrease with chronic use and this can represent a major difficulty in the long term management of IBD. However, in active IBD, leukocytes are elevated in the lesion they may be able to be a factor of IBD aggravation. Membrane filters column and leukocyte adsorbing beads have been developed which are direct blood perfusion systems for removing any desired level of leukocytes. Clinical studies with these two new models have shown good effects for active IBD. Clinical data suggest that leukocytapheresis might be an effective adjunct to therapy of IBD, to promote remission, taper conventional drug dosage and potentially should reduce the number of patients who require colectomy. The results may further understandings of the pathophysiology of IBD and this in turn should contribute to a more effective treatment of this disorder.     

Serum levels of C-reactive protein in Crohn''s disease and ulcerative colitis

Prospective measurements were made of serum C-reactive protein levels and erythrocyte sedimentation rate in sixty-four patients with Crohn's disease and fifty with ulcerative colitis. The results were related to clinical assessment of disease activity. C-reactive protein levels were raised in both groups but were significantly higher in Crohn's disease than ulcerative colitis for all categories of disease severity: with mild disease the median and range of C-reactive protein concentration were 4, 0-65 mg/l in Crohn's disease v. 0, 0-15 mg/l in ulcerative colitis, P less than 0.01; in moderate disease the values were 15, 1-100 mg/l v. 3, 0-29 mg/l respectively, P less than 0.05 and in cases of severe disease, 85, 15-183 mg/l v. 12, 2-33 mg/l respectively, P less than 0.001. Erythrocyte sedimentation rate was also higher in Crohn's disease but did not closely reflect disease activity in individual patients. C-reactive protein levels corresponded closely with clinical and pathological indices of relapse, remission and response to therapy in patients with Crohn's disease. The precise assay of serum C-reactive protein provides an objective criterion of inflammatory activity, which may be useful in the assessment, management and study of Crohn's disease.     

Serial carcinoembryonic antigen (CEA) blood levels in patients with ulcerative colitis

Fifty-seven patients with ulcerative colitis were folloued 1-49 months (mean, 18 months) with serial CEA determinations during periods of remission, mild relapses, and severe relapses. Elevated CEA titers correlated with activity and possibly extent of disease: 12% of patients with proctitis, 47% of patients with left-sided colitis, and 60% of patients with transverse or universal colitis had elevated CEA titers during a flare. Moreover, 24% of patients with mild flares and 86% of patients with severe flares had elevated CEA titers. Ninety-two percent of patients with extensive disease and severe flares had elevated CEA titers. Elevated CEA titers were correlated with histologic findings in three patients. Inflammation of mucosa was demonstrated by colonoscopy and confirmed by biopsy in one patient with persistently elevated CEA titers during clinical remission. In two other patients with active disease whose CEA titers fell prior to colectomy, marked denudation of colonic mucosa was noted. In this study, a transiently elevated CEA titer indicated either clinically active ulcerative colitis or active inflammation of colonic mucosa.     

Medical therapy in ulcerative colitis

Salazosulfapyridine(SASP) and 5-aminosalicyclic acid(5-ASA) are useful in the therapy of mildly to moderately active ulcerative colitis. 5-ASA lacks sulfa moiety of SASP and is associated with a decreased incidence of side effects. In patients with moderate or severe ulcerative colitis, glucocorticoids which may be given in conjunction with SASP or 5-ASA are beneficial in producing remission. Proctitis or left-sided colitis is effectively treated with glucocorticoid enemas. If symptoms are refractory to outpatient management, the patient should be hospitalized and given initial therapy with glucocorticoids. Total colectomy(ileo-anal anastomosis; IAA et al) must be considered for acutely ill patients not responding to intensive medical therapy. Early surgical consultation is necessary in severely ill patients.