Diagnosis, monitoring and treatment of distal colitis
Dr M. Vecchi, Gastroenterology and Gastrointestinal Endoscopy Service, IRCCS Maggiore Hospital & University of Milan, Via Pace, 9, 20122 Milan, Italy.
The diagnostic work-up of ulcerative colitis at presentation is based on the collection of clinical, microbiological, radiological, endoscopic and histologic data. Serological markers are characterized by too low a sensitivity to be commonly utilized in clinical practice. Although endoscopic and histologic features are characterized by very high sensitivity and specificity for the diagnosis of ulcerative colitis, negative stool cultures and parasites are mandatory to exclude an infectious aetiology at presentation. The treatment of choice of an acute flare-up of distal ulcerative colitis is represented by oral or topical mesalazine, or a combination of both, whereas the use of topical or systemic steroids should be restricted to patients who prove to be refractory to first-line treatments. Preliminary data suggest that the achievement of endoscopic and histologic remission after an acute flare of the disease might be associated with a prolonged remission.
Ulcerative colitis is a chronic disease characterized by mucosal inflammation of the colon, always affecting the rectum and variably extending proximally to involve parts or all of the large intestine. Fortunately, in the vast majority of patients the involvement is confined to the more distal parts of the colon; in fact, distal colitis accounts for 60–85% of all ulcerative colitis cases at diagnosis.1
In this article, we review the main diagnostic and therapeutic strategies for the management of this disease.
Definition of distal colitis
It is generally accepted that the term ‘distal colitis’ applies to those forms of ulcerative colitis involving the colon up to the mid portion of the descending colon or to the splenic flexure;2 other authors, however, define these forms as ‘left colitis’ and suggest that the term ‘distal colitis’ should be used for those diseases involving the rectum and the sigmoid colon only. Whatever definition is given, it is important to note that the upper limit of inflammatory involvement can be reached by topical therapy.3 There is also no complete agreement on whether the level of involvement should be evaluated macroscopically or histologically, although most experts agree that disease extension of a given flare-up episode should be determined according to endoscopic (macroscopic) criteria.4, 5
Clinical presentation and diagnosis
Usually, the clinical presentation of distal ulcerative colitis does not differ from that of more extensive colitis, most frequently consisting of persistent bloody diarrhoea, rectal urgency, tenesmus and a variable degree of abdominal pain.1, 2 Rectal bleeding is a constant hallmark of all forms of the disease, but it may be rarely observed in some patients with substantial colitis; diarrhoea may be absent in many patients and some of them may even present with constipation.1
Based on the above mentioned clinical features, the differential diagnosis of ulcerative colitis should include several clinical entities, listed in Table 1. The history (i.e. onset and duration of symptoms, family history of inflammatory bowel disease, recent travels, etc.) as well as some features of the patient (age, smoking habits, etc.) may orientate the diagnosis, which is usually obtained by the collection of clinical, microbiologic, radiologic, endoscopic and histologic data.
Table 1. Clinical conditions in the differential diagnosis of distal ulcerative colitis
|Collagenous or lymphocytic colitis|
Usually, blood tests are not of much help in the diagnostic work-up of a patient with suspected ulcerative colitis, although microcytic anaemia due to iron deficiency is frequent and elevation of acute phase reactants may also be observed, particularly in patients with an extensive disease. p-ANCA assay is characterized by too low a sensitivity to be included in the routine work-up of the patients, although a positive p-ANCA test may have a high positive predictive value and thus be clinically useful in selected populations.6 Stool cultures and examination for ova and parasites are mandatory to exclude an infectious cause of the colitis.
The diagnostic mainstay for ulcerative colitis is colonoscopy which is characterized by high sensitivity and specificity when compared with other suitable diagnostic tools such as barium enema.2, 4, 5 The typical endoscopic features of ulcerative colitis include rectal involvement and the continuous pattern of mucosal involvement, with loss of vascular pattern, granularity, erythema, friability and ulcerations (Table 2). Endoscopy also shows a high diagnostic yield in the differential diagnosis of ulcerative colitis vs. Crohn's colitis.7
Table 2. Endoscopic features of ulcerative colitis
|Symmetric, contiguous involvement|
|Loss of vascular pattern|
|Erosions or ulcers within diseased mucosa|
The histological findings typically feature acute and chronic inflammatory infiltration in the lamina propria, distortion and atrophy of the crypts and crypt abscesses without inflammatory involvement of submucosal layers. Histology has a recognized role in the differential diagnosis of chronic inflammatory bowel disease vs. other inflammatory colitides.8
Evaluation of disease extension and, to a lesser degree, of endoscopic activity, are further important clinical information provided by means of colonoscopy. Indeed, in patients with ulcerative colitis, the therapeutic approach is generally dictated by both the anatomic extent and the clinical activity of the disease. While the former is obtained by colonoscopy, the clinical activity of the disease is usually measured by means of Truelove and Witts criteria9 or other, more recently developed, clinical indexes.10, 11
Since clinical activity is often correlated with disease extension, patients with distal colitis usually present with mild to moderate flare-ups, although severe forms may also be observed.
Treatment of acute phases
Several options are available for the treatment of the acute phases of distal ulcerative colitis. In addition to oral formulations, topical therapies with aminosalicylates or corticosteroids have also been shown to be highly effective. Some meta-analyses and reviews have been recently published on this issue.2, 3, 12, 13
Numerous clinical trials have shown that oral mesalazine preparations are significantly superior to placebo in inducing remission in mild to moderate ulcerative colitis. The therapeutic effect appears to be to a certain extent dose-dependent, with doses of mesalazine lower than 2 g/day showing a doubtful therapeutic advantage over placebo. Induction of clinical remission, which is a complete resolution of symptoms, is reported in 40–80% of patients after 4–8 weeks of treatment.
The rapid and relevant therapeutic effect of rectal mesalazine preparations has also been known for a long time.14 Several formulations of topical mesalazine are available, including suppositories, liquid enemas, foams and gels. The choice of formulation depends on the extension of the disease and on patient's preference. One should remember that suppositories, due to their limited diffusion, are suitable only for the treatment of proctitis or distal proctosigmoiditis. In general, with topical treatment, the effect appears to be time-dependent but not dose-dependent.15 Usually, clinical remission is achieved in 70–80% of patients after 4–6 weeks. Since rectal preparations have been shown to spread up to the splenic flexure16 and appear to have a faster effect than oral therapies, they might represent the first-line choice in active distal colitis. However, there are only few papers directly comparing the two modalities (oral vs. rectal) of treatment as well as vs. the combination of both of them (oral + rectal) and the results of these papers are rather controversial.17–19 Thus, one can decide to treat a patient suffering from active distal colitis with rectal preparations only, with oral therapies only or with combined treatment mainly based on patient's preference and clinical response.
Despite a high level of therapeutic efficacy of aminosalycilates therapy, a proportion of patients will prove to be refractory to the chosen regimen. In a portion of these patients, clinical remission can be achieved just by long-term treatment; however, this approach may require a very long time before a significant clinical effect is achieved. Although, in general, rectal 5-ASA is considered superior to rectal corticosteroids in the management of distal ulcerative colitis20 an alternative approach may consist in a substitution of rectal salycilates with traditional or newer, low-bioavailability steroids. A strong therapeutic effect has also been reported with a combination of topical beclometasone dipropionate and topical aminosalicylates.21
Patients who are still refractory after these therapeutic efforts usually respond to systemic corticosteroids.
Monitoring of treatment efficacy
Most clinical trials as well as the overall clinical experience suggest that clinical improvement or clinical remission can be achieved in patients with active distal ulcerative colitis after some weeks of active treatment. However, most experts agree that a clinical contact with the patient (at least by phone) should be performed 1–2 weeks after the beginning of therapy in order to check whether the treatment is well tolerated and patient's compliance is good. This appears to be particularly needed in patients at the first attack of the disease.
There also is general agreement to perform a clinical follow-up after 4–8 weeks of treatment to check whether clinical remission has been achieved. Some observations also suggest that endoscopic and histologic follow-up should also be performed at this time, since achievement of endoscopic and histologic remission appears to be associated with prolonged remission after an acute attack.22–24
After induction of remission by one or more of the above mentioned treatment regimens, all patients with ulcerative colitis should be put on maintenance treatment. It has been known for a long time that sulfasalazine25 and its derivative mesalazine26 are highly effective to this purpose. In patients with distal colitis, this can be achieved either by oral therapies or by rectal treatment.27
A recent meta-analysis12 has shown that most remission maintenance studies using oral therapies were small in sample size. Nevertheless, the rates of remission maintenance at 1 year ranged from 60% for 2 g daily of sulfasalazine to 92% for 3.2 g daily of mesalazine, suggesting the possible presence of a mild dose-dependent effect. Rectal preparations (mesalazine 4 g daily at bedtime) showed a remission rate of 78%, with minimal decreases in efficacy with various dosing intervals, i.e. every other night or every third night dosing. No data are available on the use of low-bioavailability rectal steroids on long-term remission, while traditional steroids are not recommended due to their degree of systemic absorption and related side-effects.
Thus, it appears that rectal therapies with mesalazine are a possible option for maintenance treatment of patients with distal colitis, the main problem being the long-term acceptance of this type of treatment by the patients. This is not the case for patients with ulcerative proctitis, in which remission appears to be more effectively induced and maintained with the use of suppositories than with oral therapies, with a high degree of patient's acceptance.12
Whether maintenance of remission performed with oral therapies exerts a more protective effect than with topical ones on the proximal extension of the disease, which has been calculated to occur in up to 40% of the patients after 10 years of follow-up28 has not been fully elucidated in the published studies.
Distal ulcerative colitis, which is ulcerative colitis involving the proctosigmoid region or extending up to the splenic flexure2 is the most frequent form of this disease at diagnosis.1 The highest diagnostic yield in patients with a clinical suspect of ulcerative colitis is provided by colonoscopy with multiple biopsies; 2, 4, 5, 7, 8 however, stool cultures and search for fecal parasytes are mandatory at presentation to exclude an infectious aetiology and blood tests may be helpful in the evaluation of disease severity.
Disease extension, another important element to drive the choice among the many therapeutic options available nowadays for this condition, can also be effectively determined by colonoscopy.
Oral and rectal mesalazine preparations represent the most diffuse therapeutic approach for acute flare-ups of distal colitis.2, 3, 12, 13 Data comparing these two treatment modalities are scanty and their results rather controversial. The combined use of both treatments has also been proposed, although a clear advantage over the single treatments has not been clearly demonstrated.
Patients refractory after 4–8 weeks of mesalazine therapy should be diverted to either traditional or low bio-availability topical steroids, alone or in combination with 5-ASA.21 The use of systemic steroids should be restricted to those patients still being refractory to these treatment regimens.
In most cases, an acute flare-up of distal ulcerative colitis is associated with mild to moderate clinical activity, so that it does not represent a life-threatening condition as it may occur with severe flare-ups of more extensive forms. Nevertheless, a prompt diagnostic work-up, a correct therapeutic approach and an appropriate follow-up schedule of this condition are important, since they can shorten symptoms duration, ameliorate patient's quality of life, induce a prolonged remission and optimize the use of health resources.