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Second European evidence-based consensus on the diagnosis and management of ulcerative colitis Part 2: Current management

,2,3Department of Medicine 1, Agaplesion Markus Hospital, Wilhelm-Epstein-Str. 4, D-60431 Frankfurt/Main, GermanyDivision of Gastroenterology, Department of Medicine, MtSinai Hospital and University Health Network;University of Toronto, 600 University Avenue, Toronto, ON, Canada M5G 1X5 and University of Leuven, BelgiumReceived 26 August 2012; accepted 3 September 2012KEYWORDS

Second European evidence-based Consensus on the diagnosis and management of ulcerative colitis: Current management

Objective The inner mucus layer in mouse colon normally separates bacteria from the epithelium. Do humans have a similar inner mucus layer and are defects in this mucus layer a common denominator for spontaneous colitis in mice models and ulcerative colitis (UC)? Methods and results The colon mucus layer from mice deficient in Muc2 mucin, Core 1 O -glycans, Tlr5, interleukin 10 (IL-10) and Slc9a3 (Nhe3) together with that from dextran sodium sulfate-treated mice was immunostained for Muc2, and bacterial localisation in the mucus was analysed. All murine colitis models revealed bacteria in contact with the epithelium. Additional analysis of the less inflamed IL-10 −/− mice revealed a thicker mucus layer than wild-type, but the properties were different, as the inner mucus layer could be penetrated both by bacteria in vivo and by fluorescent beads the size of bacteria ex vivo. Clear separation between bacteria or fluorescent beads and the epithelium mediated by the inner mucus layer was also evident in normal human sigmoid colon biopsy samples. In contrast, mucus on colon biopsy specimens from patients with UC with acute inflammation was highly penetrable. Most patients with UC in remission had an impenetrable mucus layer similar to that of controls. Conclusions Normal human sigmoid colon has an inner mucus layer that is impenetrable to bacteria. The colon mucus in animal models that spontaneously develop colitis and in patients with active UC allows bacteria to penetrate and reach the epithelium. Thus colon mucus properties can be modulated, and this suggests a novel model of UC pathophysiology.

https://gut.bmj.com/content/gutjnl/63/2/281.full.pdf

Bacteria penetrate the normally impenetrable inner colon mucus layer in both murine colitis models and patients with ulcerative colitis

### 5.1 General

The general principles for treating active ulcerative colitis are to consider the activity, distribution (proctitis, left-sided, extensive,1 and pattern of disease (relapse frequency, course of disease, response to previous medications, side-effect profile of medication, extra-intestinal manifestation), before treatment decisions are made in conjunction with the patient.

#### 5.1.1 Disease activity

The principal scoring systems used for clinical trials are covered in Section 5.1.2 and have been comprehensively reviewed.2 Some additional points are clinically relevant. In clinical practice it matters most to distinguish severe ulcerative colitis necessitating hospital admission from those with mild or moderate disease who can generally be treated as outpatients. The simplest, best validated and most widely used index for identifying acute severe UC remains that of Truelove & Wi_tts 3: any patient who has a bloody stool frequency ≥ 6/day and a tachycardia (> 90 bpm), or temperature > 37.8 °C, or anaemia (haemoglobin 30 mm/h) has severe ulcerative colitis (Table 1.3). This index has been used in 20/32 studies of intensive intravenous treatment for severe UC.4 Only one additional criterion in addition to the bloody stool frequency ≥ 6/day is needed to define a severe attack.5 While these criteria have the major limitation of being unresponsive and cannot track the course of disease, they do distinguish the severe from the moderate or mild and have value in everyday practice because they are easy to use, which no other index achieves. It should be standard practice to confirm active colitis by sigmoidoscopy or proctoscopy before starting treatment. Rectal mucosal biopsy helps exclude unexpected causes of symptoms similar to active disease (such as cytomegalovirus, amoebic, or other infection, rectal mucosal prolapse, Crohn's disease, or even irritable bowel syndrome and haemorrhoidal bleeding).

#### 5.1.2 Approach

Patients should be encouraged to participate actively in …

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European evidence-based Consensus on the management of ulcerative colitis: Current management.

European-evidence-based consensus on the management of ulcerative colitis: Current management (vol 2, pg 24, 2008)

Since metronidazole (M) was found to be effective in Crohn's disease, we evaluated its efficacy in the treatment of active ulcerative colitis (UC). Forty-six outpatients with acute, nonsevere UC were studied. Forty-two concluded the trial. Twenty-three received M 1.35 g/day and 19 received sulfasalazine (S) 4.5 g/day for 28 days in a randomized double-blind study. Six of 23 receiving M improved (26%) as against 13 of 19 patients receiving S (68%) (p less than 0.01). No significant side effects were noted. We conclude that M is ineffective in the therapy of an acute attack of UC.

A comparative study of metronidazole and sulfasalazine in active, not severe, ulcerative colitis. An Israeli multicenter trial.

In a double-blind, randomized trial, we tested the effectiveness of metronidazole (0.6 g/day) against sulfasalazine (2 g/day) in the maintenance of remission in patients with ulcerative colitis. The patients were in remission for 1-11 months at entry to trial, which lasted for 12 months. Forty patients entered the trial and 33 completed it. Metronidazole was found to be slightly more effective than sulfasalazine, a difference statistically significant only at 12 months. Six patients also completed a crossover trial. Remission was maintained for 12 months in 3 patients by metronidazole and in none of the 6 by sulfasalazine. No significant side effects were noted, and in particular, no paresthesias were reported. This trial, as well as our previous one, suggests that metronidazole may be useful in the maintenance of remission in patients with ulcerative colitis, but that it is ineffective in the therapy of the acute attack.

G Leichtman

Papers

A comparative study of metronidazole and sulfasalazine in active, not severe, ulcerative colitis. An Israeli multicenter trial.

A comparison of metronidazole and sulfasalazine in the maintenance of remission in patients with ulcerative colitis.