Metachronous occurrence of collagenous colitis and ulcerative colitis.

Collagenous colitis and ulcerative colitis are distinct disorders. A 67 year old woman with clinical and histological evidence of collagenous colitis had an abrupt symptomatic exacerbation while taking anti-inflammatory treatment with sulphasalazine and prednisone. Repeat colorectal endoscopy showed active mucosal inflammation and colonic biopsy specimens were consistent with active ulcerative colitis. After bowel rest, total parenteral nutrition, intensification of the anti-inflammatory regimen, and withdrawal of non-steroidal anti-inflammatory drugs (which she had taken continuously for osteoarthritis) diarrhoea abated. Colorectal biopsy specimens obtained when the patient's symptoms had improved showed inactive ulcerative colitis with no evidence of collagenous colitis. This may be the first case to be reported of the metachronous association of collagenous and ulcerative colitis.     

Early aggressive therapy for severe extensive ulcerative colitis

The current ulcerative colitis （UC） treatment algorithm involves a step-up therapeutic strategy, mainly aiming at inducing and maintaining its clinical remission. Although this therapeutic strategy may seem to be cost-efficient and reduce the risk of side effects, recent trials and case reports have shown that top-down therapy using infliximab induces a rapid clinical response, enhances patient quality of life, promotes mucosal healing, reduces surgeries and indirect cost of treatment for patients with severe UC. Moreover, since long-term treatment with infliximab is safe and well tolerated, early aggressive top-down therapeutic strategy may be a more effective approach, at least in a subgroup of severe extensive UC patients.     

Progression of collagenous colitis to ulcerative colitis

Collagenous colitis is a form of microscopic colitis that results in chronic watery diarrhea. The disorder predominantly affects middle-aged women, and its course tends to be benign. It is not thought to be a precursor of overt inflammatory bowel disease; however, apparent progression to ulcerative colitis has been reported on one previous occasion. We describe two further patients with symptoms and histologic features of collagenous colitis who subsequently developed ulcerative colitis. The first patient developed ulcerative colitis 13 months after diagnosis of collagenous colitis, although she gave a 23-year history of profuse watery diarrhea, which had not been adequately investigated. In the second patient, collagenous colitis was diagnosed soon after the onset of watery diarrhea, and 12 months later, progression to ulcerative colitis was documented. Both patients tested positive for perinuclear antineutrophil cytoplasmic antibody after they developed ulcerative colitis; the first patient was initially negative. In conclusion, these two cases, in addition to the one other in the literature, suggest that collagenous colitis and ulcerative colitis may represent extremes in the spectrum of inflammatory bowel disease and that collagenous colitis may evolve to ulcerative colitis. Therefore, progression to ulcerative colitis should be considered in any patient with known collagenous colitis whenever bloody diarrhea occurs, or if red cells, as well as white cells, are noted on stool microscopy.     

Lansoprazole-associated collagenous colitis： Diffuse mucosal cloudiness mimicking ulcerative colitis

There have only been a few reports on lansoprazole-associated collagenous colitis. Colonic mucosa of collagenous colitis is known to be endoscopically normal. We present a case of collagenous colitis where the mucosa showed diffuse cloudiness mimickin gulcerative colitis. A 70-year-old woman developed watery diarrhea four to nine times a day. She had interstitial pneumonia at 67 and reflux esophagitis at 70 years. Lansoprazole 30 mg/d had been prescribed for reflux esophagitis for nearly 6 mo. Lansoprazole was withdrawn due to its possible side effect of diarrhea. Colonoscopy disclosed diffuse cloudiness of the mucosa which suggested ulcerative colitis.Consequently sulfasalazine 2 g/d was started. The patient＇s diarrhea dramatically disappeared on the following day. However, biopsy specimens showed subepithelial collagenous thickening and infiltration of inflammatory cells in the lamina propria, confirming the diagnosis of collagenous colitis. One month after sulfasalazine therapy was initiated, colonoscopic and histological abnormalities resolved completely. Fivemonths later the diarrhea recurred. The findings on colonoscopy and histology were the same as before, confirming a diagnosis of collagenous colitis relapse. We found that the patient had begun to take lansoprazole again 3 mo ahead of the recent diarrhea.Withdrawal of lansoprazole promptly resolved the diarrhea. Endoscopic and histological abnormalities were also completely resolved, similar to the first episode. Retrospectively, the date of commencement of sulfasalazine and discontinuation of lansoprazole in the first episode was found to be the same. We conclude that this patient had lansoprazole-associated collagenous colitis.     

Recurrent myopericarditis with extensive ulcerative colitis

A 26-year-old man with ulcerative colitis was independently evaluated in different emergency rooms on two occasions, separated by six years, for episodes of severe chest pain consistent with myopericarditis. Cardiac enzyme and electrocardiographic changes were accompanied by extensive colonic inflammatory changes. Treatment with corticosteroids led to resolution. While his cardiac findings were initially believed to be caused by a previously reported drug hypersensitivity to mesalamine (5-aminosalicylate), sulphasalazine was tolerated. Recurrent myopericarditis with ulcerative colitis appears to be rare, but responsive to steroids. It may occur more often than is currently appreciated and may lead to fatal arrhythmias or cardiac failure.     

Early colectomy in severe ulcerative colitis.

Before 1 February 1967 patients with severe attacks of ulcerative colitis were usually operated on after a prolonged period of medical treatment, and the mortality was 22%. During a 7-year period, beginning 1 February 1967, early colectomy has been perfomed in 21 patients with toxic megacolon and 58 patients with fulminating colitis. Immediate mortality in these 79 patients was 1.2% (one death). Two more patients died in connection with secondary operations. Thus the overall operative mortality in the present series was 3.7%.     

Predicting outcome in severe ulcerative colitis.

BACKGROUND: Simple criteria are needed to predict which patients with severe ulcerative colitis will respond poorly to intensive medical treatment and require colectomy. AIMS: To find out if the early pattern of change in inflammatory markers or other variables could predict the need for surgery and to evaluate the outcome of medical treatment during one year follow up. PATIENTS: 51 consecutive episodes of severe colitis (Truelove and Witts criteria) affecting 49 patients admitted to John Radcliffe Hospital, Oxford. METHODS: Prospective study monitoring 36 clinical, laboratory, and radiographic variables. All episodes treated with intravenous and rectal hydrocortisone and 14 of 51 with cyclosporine. RESULTS: Complete response in 21 episodes (< or = 3 stools on day 7, without visible blood), incomplete response in 15 (> 3 stools or visible blood on day 7, but no colectomy), and colectomy on that admission in 15. During the first five days, stool frequency and C reactive protein (CRP) distinguished between outcomes (p < 0.00625, corrected for multiple comparisons) irrespective of whether patients or the number of episodes were analysed. It could be predicted on day 3, that 85% of patients with more than eight stools on that day, or a stool frequency between three and eight together with a CRP > 45 mg/l, would require colectomy. For patients given cyclosporine, four of 14 avoided colectomy but two continued to have symptoms. After admission, complete responders remained in remission for a median nine months and had a 5% chance of colectomy. Incomplete responders had a 60% chance of continuous symptoms and 40% chance of colectomy. CONCLUSIONS: After three days intensive treatment, patients with frequent stools (> 8/day), or raised CRP (> 45 mg/l) need to be identified, as most will require colectomy on that admission. The role of cyclosporine for treating severe colitis has yet to be defined. After seven days' treatment, patients with > 3 stools/day of visible blood have a 60% chance of continuous symptoms and 40% chance of colectomy in the following months.     

Acute appendicitis in inactive extensive ulcerative colitis

Appendectomy is associated with a reduced risk of developing ulcerative colitis (UC). In addition, there may be appendicular involvement in UC in patients with extensive or even left-sided disease. However, no data are available on the incidence, clinical presentation and outcome of acute appendicitis in patients previously diagnosed with UC. The impact of appendectomy in this subset of patients also remains to be determined. We describe 2 cases of acute appendicitis in the setting of inactive extensive ulcerative colitis and compare their histologic features with those of the surgical specimens of 2 further UC patients colectomized for refractory and extensive disease.     

Small bowel gas in severe ulcerative colitis.

The prognostic significance of excess small bowel gas on a plain abdominal radiograph has been assessed in 75 patients with severe attacks of ulcerative colitis requiring intravenous hydrocortisone. The radiographs were reviewed without knowledge of the subsequent outcome. Small bowel distension was defined as the presence of three or more loops of gas filled small bowel. Forty two patients responded to medical treatment and 33 underwent colectomy. The two groups were comparable for age, sex, and length of history. The surgical group had more extensive disease. Of those who did well on medical therapy, 18 (42.9%) had small bowel distension compared with 24 of 33 (72.7%) who failed medical therapy. The difference was significant (p less than 0.05, odds ratio = 3.55, 95% confidence interval of 2.27-5.87). Of the 24 patients with small bowel distension who came to surgery, five had more than four loops of gas filled small bowel. This degree of distension was not seen in any of the patients settling on medical therapy. Thus the presence of small bowel distension on a plain abdominal radiograph in a patient with severe ulcerative colitis may predict a poor response to medical therapy.     

Colonic production of nitric oxide gas in ulcerative colitis, collagenous colitis and uninflamed bowel

BACKGROUND: Nitric oxide (NO) produced in excess by the inflamed human colon is generally considered a pathway of mucosal damage. In an attempt to quantify colonic mucosal production of NO in various forms of colitis we performed 'steady-state' gas perfusion of whole colon in 11 patients with ulcerative colitis, 10 patients with collagenous colitis and 20 controls with uninflamed mucosa. METHODS: The tip of a Teflon tube was placed in the caecum during colonoscopy. Subsequently, argon was infused at a constant rate for 70-180 min. Argon and NO in gas sampled from the rectum were measured by neutron activation analysis and the chemiluminescence technique, respectively. RESULTS: The use of argon as a marker of colonic NO output was justified by complete recovery (96%+/-2; mean +/- s(x); n = 5) of argon in gas collected from the rectum and a constant output of NO at varying perfusion rates (25, 50 and 75 ml/min coefficient of variation 21%; n = 6). In patients with ulcerative colitis, colonic output of NO was 10-fold higher (P < 0.001) than in controls and positively correlated (P < 0.01) to indices of disease activity. In patients with collagenous colitis, colonic output of NO was 50-fold higher (P < 0.01) than in controls during periods with watery diarrhoea (n = 6), but within the range observed in ulcerative colitis in the absence of diarrhoea (n = 4). CONCLUSIONS: Argon gas perfusion of whole colon using chemiluminescence technique for measurement of NO is a reliable method for quantification of colonic mucosal NO production. Increased colonic production of NO in collagenous colitis, which exceeds the output observed even in extensive ulcerative colitis, militates against the theory that NO per se is a cause of mucosal injury.     

Medical management of severe ulcerative colitis

The medical management of patients with severe ulcerative colitis requires initial stabilization, careful and repeated evaluations to exclude confounding or coexisting diagnoses, and timely delivery of appropriate medications. Medical therapies for these patients are potent but may be toxic, and administration must be done by experienced medical professionals, with adequate access to appropriate laboratory, radiographic, endoscopic, and surgical facilities. Patients who fail to respond to high-dose intravenous corticosteroids in a timely basis should be evaluated for cyclosporin therapy, or proceed to surgery. The promise of newer, investigational therapies to induce and maintain remission must be borne out by large controlled trials.     

Medical management of severe ulcerative colitis

Conclusions Providing some simple rules are applied, severe attacks of ulcerative colitis can be effectively managed with virtually no mortality. A proportion of patients (1 in 5) will come to surgery but the guidelines for surgical intervention are now clear. Joint management between medical and surgical teams is important and, possibly, the combination of a surgically aggressive physician with a medicallyminded surgeon is the ideal.     

Management of acute severe ulcerative colitis

Acute severe ulcerative colitis is a potentially lethal condition that requires a pro-active approach with either effective medical treatment or timely colectomy. Although intravenous corticosteroids remain the first line treatment, in patients not responding after 3-5 days rescue medical therapy with either intravenous (IV) cyclosporine 2 mg/kg or infliximab 5 mg/kg IV should be considered. Controlled evidence supports the use of both treatments but medical rescue therapy should not defer the decision for colectomy in patients with inadequate response. Providing clear guidance for the choice between both agents is impossible due to the lack of comparative trials. The better short-term safety profile and the option for maintenance treatment favour infliximab specifically in patients already exposed to immunosuppressives. The rapid onset of action and the short half-life are advantages of cyclosporine in patients with imminent risk of colectomy. Even if cyclosporine and probably also infliximab only postpone colectomy in at least half of the patients, elective colectomy in a later stage of the disease may offer better outcomes. Whereas prolonged exposure to steroids predisposes to an increased rate of peri-operative complications it is still debated whether cyclosporine or infliximab increase peri-operative morbidity in ulcerative colitis.     

Management of acute severe ulcerative colitis

Ulcerative colitis is a chronic relapsing and remitting inflammatory disorder that can generally be managed successfully with maintenance oral medications. However, approximately 15% of patients with ulcerative colitis will develop a severe exacerbation and require hospitalization. While many patients with acute severe ulcerative colitis will respond to a short course of intravenous corticosteroids, up to a third will fail to improve. In these patients with steroid-refractory colitis, the choice is between rescue medical therapy with ciclosporin or infliximab, or surgery. Well-timed rescue medical therapy is generally safe when administered by experienced physicians, and is effective in the majority of cases. Surgery is unavoidable in some cases, but is the treatment of choice in others. While ileal pouch–anal anastomosis offers the prospect of life without a permanent ileostomy, there are issues with its long-term functional outcome.     

Current management of severe ulcerative colitis

Approximately 15% of patients with ulcerative colitis develop an acute attack of severe colitis, and 30% of these patients require colectomy. Severe ulcerative colitis is therefore considered a medical emergency, the management of which requires close collaboration between gastroenterologists and surgeons. The mortality rate for patients with severe ulcerative colitis is now <1% in specialist centers, but it was high before intravenous steroid therapy and early surgery were introduced; indeed, mortality is still high in nonspecialized centers. As colectomy severely affects quality of life, therapy with intravenous ciclosporin and, more recently, infliximab has been introduced to try to avoid the need for surgery. Ciclosporin induces short-term remission, but the long-term benefit remains unsatisfactory as colectomy is often only delayed. A significant short-term reduction in the colectomy rate has, however, been observed after infliximab treatment. The use of infliximab versus ciclosporin in patients with severe ulcerative colitis remains to be defined. The timing of surgery remains a cardinal decision in the management of severe ulcerative colitis; increased morbidity resulting from prolonged ineffective medical treatment and, therefore, a delay in surgical treatment should be avoided.     

Management of acute severe ulcerative colitis

The management strategy of acute severe ulcerative colitis has evolved over the past decade from being entirely restricted to twin choices of intravenous steroids or colectomy to include colon rescue therapies like cyclosporin as well as infliximab. However it still remains a medical emergency requiring hospitalization and requires care from a multidisciplinary team comprising of a gastroenterologist and a colorectal surgeon. The frame shift in management has been the emphasis on time bound decision making with an attempt to curtail the mortality rate to below 1%. Intravenous corticosteroids are the mainstay of therapy. Response to steroids should be assessed at day 3 of admission and partial/non-responders should be considered for alternative medical therapy/surgery. Medical rescue therapies include intravenous cyclosporin and infliximab. Cyclosporin is administered in a dose of 2 mg/kg per day and infliximab is administered as a single dose intravenous infusion of 5 mg/kg. Approximately 75% patients have short term and 50% patients have long term response to cyclosporin. Long term response to cyclosporin is improved in patients who are thiopurine naïve and are started on thiopurines on day 7. Infliximab also has a response rate of approximately 70% in short term and 50% in long term. Both cyclosporin and infliximab are equally efficacious medical rescue therapies as demonstrated in a recent randomized control trial. Patients not responding to infliximab or cyclosporin should be considered for colectomy.     

Efficacy of cyclosporin in severe ulcerative colitis attack.

BACKGROUND/AIMS: Cyclosporin-A is used as a alternative medical therapy in steroid resistant ulcerative colitis with severe activity. In spite of its known efficacy, the long term effects of are not entirely clear. METHODS: The records of 13 steroid resistant patients treated with cyclosporin-A were retrospectively assessed. Cyclosporin-A had been prescribed orally at a dose of 8 mg/kg/day in four patients and intravenously, 4mg/kg/day in nine patients. Intravenous therapy was changed to oral therapy after one week and patients also received 5-ASA and azathioprine. Steroid treatment was tapered. RESULTS: Ten patients responded to treatment in a mean of nine days (range: 2-30 days). Three patients who did not respond underwent total colectomy on day seven, 11 and 19 of therapy. The 10 patients who initially responded received the drug for an average of 4.9 months; four of these relapsed during and one relapsed soon after discontinuation of therapy. Four of the five patients who relapsed underwent colectomy and the one patient who did not accept surgical intervention continued medical therapy. The remaining five patients (38% of the total group; 50% of the patients who initially responded) remained in remission at the end of an average 17 month follow up period. CONCLUSIONS: Cyclosporin-A therapy in severe ulcerative colitis that is resistant to steroids, provides initial remission in 80% of patients and allows 40% to retain their colon for one year.