IgG subclasscontaining cells in the human large bowel of normal controls,non-IBD colitis,and ulcerative colitis

IgG subclass-containing cells in colonic mucosa were examined in three groups; 1) normal controls 2) cases of ulcerative colitis (UC) 3) cases of colitis excluding UC and Crohn’s disease (non-IBD colitis) by indirect immunoperoxidase staining method using mouse anti-IgG subclass monoclonal antibodies. The numbers (and proportions) of IgG1, IgG2, IgG3, and IgG4-containing cells in normal colonic mucosa was 80±29/mm² (44.6%), 44±21 (24.1%), 44±24 (23.7%), 13±10 (7.7%), respectively. The proportion of IgG subclass-containing cells in normal colonic mucosa was different from the known proportion of IgG subclass in serum. In UC, the numbers of all IgG subclasses-containing cells were significantly increased compared to controls and non-IBD colitis. However, only IgG1-containing cells were increased in proportion (50.3%) compared to normal controls. In non-IBD colitis, the numbers of IgG1- and IgG2-containing cells were increased compared to the controls, but the increases were less than UC, and there was no difference in the proportion of IgG subclass compared to normal controls. The differences in the numbers and in the proportions of IgG subclass-containing cells between UC and non-IBD colitis may reflect differences in the underlying disease process. This work was partly supported by a grant from the Research Committee for Intractable Intestinal Disease, Ministry of Welfare, Japan.     

A patient with rectal cancer associated with ulcerative colitis in whom endoscopic ultrasonography was useful for diagnosis

Endoscopic ultrasonography (EUS) was helpful for the diagnosis of rectal cancer associated with ulcerative colitis. The patient was a 38-year-old Japanese man with a 19-year history of relapsing-remitting type ulcerative colitis involving the entire colon. Routine colonoscopy revealed multiple polypoid prominences in the upper portion of the rectum. EUS revealed a hypoechoic mass in the submucosa beneath and around the polypoid lesion on the most oral side. Signet ring cells were found in a biopsy specimen from this lesion. Subtotal colectomy was performed. A depressed lesion was observed around the prominence on the most oral side; histologically, this lesion was poorly differentiated mucinous and signet ring cell carcinoma extending into the subserosa. The polypoid lesion on the most anal side was well differentiated adenocarcinoma, which was limited to the mucosa. Our findings suggest that EUS is helpful for detecting invasive cancer associated with ulcerative colitis. Received: April 22, 1998 / Accepted: January 22, 1999     

Infiltration of peroxidase-producing eosinophils into the lamina propria of patients with ulcerative colitis

Little information is available to explain the pathogenesis of ulcerative colitis (UC). In this study, we focused on eosinophils in the lamina propria of the mucosa of patients with UC in the active phase. Biopsy specimens were taken from 17 patients with UC in the active phase, 17 in the inactive phase, and 20 control patients, and submitted for histochemical staining for peroxidase and chloroacetate esterase for microscopic examination. Both peroxidase-producing and chloroacetate esterase-producing cells in the lamina propria increased markedly in the active phase (8.3 ± 3.1/0.01 mm² and 6.6 ± 2.7/0.01 mm², respectively), compared with values in the inactive phase (0.8 ± 0.6/0.01 mm² and 1.3 ± 0.6/0.01 mm²) or in the controls (1.3 ± 0.8/0.01 mm² and 1.3 ± 0.4/0.01 mm²). Triple staining for peroxidase, chloroacetate esterase, and nonspecific esterase in the specimens revealed that the peroxidase-producing cells constituted a different population from that of neutrophils, macrophages/monocytes, or basophils. A monoclonal antibody specific for eosinophil peroxidase stained almost all infiltrated peroxidase-producing cells. These results indicated that eosinophils with strong peroxidase activity had infiltrated the lamina propria in UC, suggesting an allergic background and the involvement of released peroxidase in the mucosal damage characteristic of UC. (Received Mar. 28, 1997; accepted July 25, 1997)     

溃疡性结肠炎患者肠道菌群变化与细胞因子、TLRs分子表达的相关性研究

目的探讨溃疡性结肠炎患者肠道菌群变化与细胞因子、TOLL样受体(Toll-like receptors,TLRs)分子表达的相关性。方法将2015年6月—2016年12月在山东省医学科学院第三附属医院确诊并接受治疗的溃疡性结肠炎患者78例作为试验组,同时选择未患溃疡性结肠炎的80例健康者作为对照组。分别对试验组和对照组进行肠道菌群检测,肠黏膜TLR2、TLR4、TLR5、TLR9分子表达检测和外周血IL-4、IL-6、IL-17、IL-23、TNF-α等炎性细胞因子表达检测,分析炎性细胞因子和TLRs表达与肠道菌群变化的关系。结果试验组双歧杆菌、乳杆菌含量明显低于对照组(P均0.05),拟杆菌、肠杆菌、肠球菌、梭杆菌含量明显高于对照组(P均0.05);试验组肠黏膜组织中TLR2、TLR4、TLR5、TLR9表达明显高于对照组(P均0.05);试验组外周血IL-4表达低于对照组,IL-6、IL-17、IL-23、TNF-α等炎性细胞因子表达高于对照组(P均0.05)。Pearson相关性分析显示,TLR2、TLR4、TLR5、TLR9表达与拟杆菌、肠杆菌、肠球菌含量呈正相关,与双歧杆菌、乳杆菌含量呈负相关;与IL-6、IL-17、IL-23、TNF-α表达呈正相关,与IL-4表达呈负相关。结论溃疡性结肠炎患者正常肠道菌群平衡被打破,促炎因子表达增加,抑炎因子表达减少,TLRs分子表达增加。肠道菌群紊乱可能通过增强TLRs分子表达来促进促炎因子的分泌,介导肠黏膜炎性反应。     

Steroid-refractory severe ulcerative colitis responding to cyclosporine and long-term follow-up

We report a case of steroid-refractory ulcerative colitis, treated with cyclosporine, in a 38-year-old woman with a 13-year history of ulcerative colitis. No remission was achieved with treatments that included intravenous hyperalimentation, sulfasalazine, and intensive parenteral prednisolone therapy for 4 weeks. Intravenous infusion of cyclosporine was performed because the patient refused to undergo surgery. Her condition improved dramatically and colectomy was avoided. She has been maintained on oral cyclosporine and azathioprine since steroids were discontinued, and she has remained in clinical and endoscopic remission for 2 years. The side effects were not significant, but mild paresthesia in both hands and mild hypertension, which was controlled by anti-hypertensives. Cyclosporine seems to be an effective treatment for patients with steroid-refractory severe active ulcerative colitis in whom colectomy seems inevitable. We believe further clinical trials of the treatment are warranted. (Received July 25, 1997; accepted Nov. 28, 1997)     

Treatment of fulminant ulcerative colitis with cyclosporine A

Abstract

Objective. Fulminant ulcerative colitis not responding to high doses of corticosteroids remains a clinical challenge. Intravenous infusion of cyclosporine A (CyA) has shown an excellent short-term response, but its use has been restricted by potential serious adverse events and reports of high short- and long-term colectomy rates. The purpose of this study was to report on the Oslo experience with CyA in fulminant ulcerative colitis. Material and methods. Between 1993 and 2006, intravenous CyA (5 mg/kg) was administered to 18 patients with fulminant ulcerative colitis. Responders were discharged under a 6 months' course of oral CyA. Patients were prospectively followed at 2, 6, 12 and 24 months after discharge. Results. Fifteen patients (83%) responded to intravenous CyA treatment. On follow-up at 2, 6, 12 and 24 months, the colectomy-free rates were 72%, 67%, 61% and 56%, respectively. After a median follow-up of 60.3 months (range 1.7–146), 8 patients (44%) still had avoided having to undergo a colectomy. All patients had at least one relapse during follow-up. Only one patient had to discontinue CyA owing to adverse events. Conclusion. At our institution, CyA treatment of fulminant ulcerative colitis is an effective and safe treatment.     

The beneficial effect of azathioprine on maintenance of remission in severe ulcerative colitis

Background. The search is on to find more effective drug regimens for patients with severe ulcerative colitis, as conventional drugs such as sulfasalazine and its congeners fail to prevent relapse in a significant number of patients. Azathioprine has also been reported to be useful as a steroid-sparing drug in patients who suffer from frequent relapses. As these drugs when used individually fail to sustain remission in a significant number of patients, we evaluated the combination of these two drugs. Methods. Thirty-five newly diagnosed patients with severe ulcerative colitis were randomized into two groups; group A (combination therapy) received sulfasalazine and azathioprine, while group B (sulfasalazine monotherapy) received sulfasalazine and placebo. In addition, all the patients received steroids initially to achieve clinical remission. The patients were followed-up for a period of 1 year. The therapeutic outcome was measured by the number of patients who suffered relapse in each group. Results. All the patients completed the 1-year study period. While 4 patients (23.5%) in group A suffered relapse of disease, 10 (55.6%) in group B suffered relapse, the difference being statistically significant. The relapse-free period was also significantly longer in group A. Conclusions. Combination therapy (sulfasalazine and azathioprine) is more effective than sulfasalazine and placebo in the maintenance of remission in patients with severe ulcerative colitis. Received: November 20, 2000 / Accepted: September 14, 2001     

Right-sided ulcerative colitis

This report describes a case of right-sided ulcerative colitis in which multiple shallow ulcers and erosion with symmetric luminal stenosis were distributed segmentally from the ascending colon to the cecum, with a skip lesion composed of superficial erosions in the right half of the transverse colon. Both the rectum and the left colon were spared at the time of onset. Biopsies taken from the lesions showed non-specific inflammation, while those from the rectum and sigmoid colon showed no abnormal findings. A 5-year follow-up study was made based on radiography and endoscopy. Other inflammatory bowel diseases, such as Crohn's disease, tuberculosis, Yersinosis, Behçet's disease, and ischemic colitis were all ruled out, based on the macroscopic and microscopic findings as well as the clinical course. To our knowledge, this is the first report of right-sided ulcerative colitis that has been followed for a long period.     

Tacrolimus in corticosteroid-resistant ulcerative colitis

We report a case of refractory ulcerative colitis treated with tacrolimus. The patient was a 73-year-old woman with a 45-year history of ulcerative colitis. An attack unresponsive to intravenous corticosteroid therapy occurred when she was age 73. Leukocytapheresis therapy was attempted, but was discontinued because of the patient's poor general condition. Cyclosporine A therapy brought about fair control of the disease. A liver injury that was suspected to be associated with this agent, however, occurred within 5 weeks of its initiation. At that time, the cyclosporine A was discontinued and azathioprine treatment was started. Within 6 weeks, signs of exacerbation of the ulcerative colitis became apparent. Tacrolimus administered at that time brought about remission of the disease, and the corticosteroid dose was then reduced. Tacrolimus, like cyclosporine A, appears to be effective for the treatment of attacks of ulcerative colitis. Received: August 23, 1999 / Accepted: January 28, 2000     

Gastroduodenitis associated with ulcerative colitis

Background Ulcerative colitis (UC) is regarded as confined to the colorectum; however, there are several case reports showing upper gastrointestinal involvement. The aim of this study was to examine the prevalence and characteristics of gastroduodenitis associated with UC (GDUC). Methods Esophagogastroduodenoscopy with biopsies was prospectively performed on 250 UC patients (134 men, 116 women; mean age, 42 years; 162 with colectomy, 163 with pancolitis). Criteria for GDUC were created on the basis of endoscopic and histological comparisons with non-UC controls, and the prevalence and characteristics were statistically analyzed. Results GDUC was defined endoscopically as friable mucosa (erosive or ulcerative mucosa with contact or spontaneous bleeding), granular mucosa (multiple white spots almost without a red halo), or, conditionally, multiple aphthae (multiple white spots surrounded by a red halo, clinically excluding other disorders such as Crohn’s disease). The prevalence of GDUC was 19/250 (7.6%). The clinical characteristics included more extensive colitis, lower dose of prednisolone, higher prevalence of pouchitis, and longer postoperative period. In our population, the presence of pancolitis and a lower dose of prednisolone were significant risk factors for developing GDUC in multivariate analysis. Conclusions The high prevalence of GDUC suggests that the gut inflammatory reaction in UC may not be restricted to the large intestine. Administered steroids might conceal GDUC, and more aggressive UC such as active pancolitis may be related to the development of GDUC.     

Colonic malacoplakia: Unusual association with ulcerative colitis

Abstract A 44 year old Chinese female with malacoplakia of the colon associated with ulcerative colitis was presented. The patient showed typical histological, electron microscopic and X-ray micro-analysis findings of malacoplakia. The malacoplakia gradually disappeared after discontinuation of high-dose systemic steroid prescribed by private practitioner for the ulcerative colitis. A review of the 26 previously reported cases of malacoplakia of the colon is also included. Coupled with the clinical events of this patient, it appears that malacoplakia is likely to be secondary to immunosuppression, due to drugs, malignant or debilitating diseases.     

Pyoderma gangrenosum complicating ulcerative colitis: Successful treatment with methylprednisolone pulse therapy and cyclosporine

A 32-year-old woman with ulcerative colitis had a relapsed of pyoderma gangrenosum during puerperium. Both the pyoderma gangrenosum and ulcerative colitis had been well controlled with oral prednisolone, but ulcerative colitis relapsed in pregnancy, and pyoderma gangrenosum relapsed in the puerperium. The pyoderma gangrenosum responded to methylprednisolone pulse therapy initially, but relapsed when prednisolone was tapered. A second trial of pulse therapy combined with cyclosporine resulted in complete remission of the pyoderma gangrenosum, and no recurrence was recognized after prednisolone was tapered. This is a very rare case of successful treatment with methylprednisolone pulse therapy combined with cyclosporine for pyoderma gangrenosum complicating ulcerative colitis. (Received May 6, 1997; accepted Sept. 26, 1997)     

Progression of primary biliary cirrhosis after proctocolectomy for ulcerative colitis

We report a case of progression of primary biliary cirrhosis (PBC) after proctocolectomy for ulcerative colitis. A 43-year-old woman underwent a total proctocolectomy after being diagnosed with ulcerative colitis. In the course of the preoperative investigation, liver function test results were within the normal range. Four months after the proctocolectomy, the patient showed a high level of alkaline phosphatase (2398 IU/l) and a positive anti-mitochondrial antibody titer (>1 : 160). There were no associated symptoms. A liver biopsy demonstrated expansion of all portal areas by infiltrates of lymphocytes and histiocytes. These appearances indicated chronic biliary disease and were compatible with PBC. The association of PBC and ulcerative colitis is rare. However, a review of the recent literature suggests that PBC and ulcerative colitis may be associated; this combination should be kept in mind. Received: October 4, 1999 / Accepted: February 25, 2000     

Unusual cerebral complication associated with ulcerative colitis

A case of ulcerative colitis complicated with convulsive seizure is reported. Magnetic resonance imasing studies strongly suggested cerebral vasculitis was the main cause of this episode.     

Rheumatoid arthritis associated with ulcerative colitis

This report describes a 58-year-old man with rheumatoid arthritis (RA) and interstitial pneumonia who suffered from low-grade fever, abdominal pain, and bloody diarrhea 16 months after the diagnosis of RA. Ulcerative colitis (UC) was diagnosed, based on endoscopic and histological findings. RA associated with UC is rare and the underlying mechanism is unknown. We discuss here whether vasculitis and HLA class may play some role in the association of RA with UC.     

Evaluation of the clinical course of acute attacks in patients with ulcerative colitis through the use of an activity index

Background. Because it is not easy to make a clinical decision regarding surgical treatment in patients with acute attacks of ulcerative colitis, an objective, simple, criterion is needed to determine the optimum timing for colectomy. The aim of this study was to retrospectively examine to what extent an activity index (AI) can evaluate the clinical course in such acute attacks. Methods. One hundred and twenty-seven patients with moderate or severe attacks of ulcerative colitis were examined. AI values and the decline in AI values were compared between surgical and nonsurgical groups after 1 week and 2 weeks of medical therapy. To evaluate the clinical course of acute attacks, cutoff AI values were set at every 10 points between values of 180 and 210. The positive predictive value for surgery was examined. Results. AI values in the surgical group were significantly higher than those in nonsurgical group at pretreatment, and after 1 or 2 weeks of medical therapy. The decline of AI values in the nonsurgical group was significantly higher than that in the surgical group after 1 or 2 weeks of medical therapy. At pretreatment, the prediction of colectomy was less than 50% at any of the cutoff values. After 1 week of therapy, approximately 60% of patients with an AI value greater than any of the cutoff AI values required colectomy. After 2 weeks of therapy, 30 of 43 (70%), 28 of 38 (74%), 24 of 29 (83%), and 17 of 21 (81%) patients with AI values greater than 180, 190, 200, and 210, respectively, required colectomy. Overall accuracy was 86%, 87%, 88%, and 83% for cutoff AI values of 180, 190, 200, and 210, respectively. Because the overall accuracy and positive predictive value for colectomy at AI values of 200 were significantly higher than these parameters at other AI values after 2 weeks of therapy, an AI value of 200 was regarded as the cutoff value most able to predict colectomy. Conclusions. We concluded that patients with an AI value in excess of 200 after 2 weeks of medical therapy would require surgical treatment. Received: December 6, 2000 / Accepted: July 20, 2001