Rectal-sparing type of ulcerative colitis predicts lack of response to pharmacotherapies

Ulcerative colitis (UC) is known as an immune disorder of the colon that generally involves the rectum. UC is typically classified into several categories based on the extension of colitis, which includes proctitis, including left-side colitis, pan-colitis, or segmental colitis [1]. Generally, inflammation arising from distal proctitis can diffusely or continuously extend to the proximal colon. However, an atypical distribution of inflamed mucosa has been noted previously in various conditions, such as the rectal-sparing type (RST), even in the absence of topical treatment for proctitis [2]. In a previous report, although RST could be recognized in endoscopic examinations, histological inflammation always existed in biopsy specimens [3]. Therefore, the RST may be indicated by relatively minor inflammatory findings in an endoscopic examination.

Previous reports have suggested an association between primary sclerosing cholangitis (PSC) and the RST [4‐6]. PSC exhibits a high risk of colitis-associated cancer [7‐9] and pouchitis after a restorative proctocolectomy [10]. Although remission of rectal inflammation can be achieved via topical treatments, including aminosalicylate and corticosteroids, the RST may be observed at the time of disease onset, even in the absence of any treatments; the condition is also more frequently noted in pediatric patients [11‐14]. Although RST patients exhibited a high risk for refractory disease in a previous report [15], the clinical significance of the RST remains unknown.

We recently treated several UC patients with the RST who required urgent/emergent surgery. Therefore, we retrospectively reviewed clinical records to evaluate clinical features of RST patients and the association between the RST and failure of medical therapy (i.e., need for colectomy).

The RST of UC may occur at some point during the medical treatment of UC in as many as 44% of cases [17]. This result may indicate that only the timing of the disease or the extent of disease may be revealed by treatment modifications. According to a previous report, the RST exclusively exhibits one course of disease progression because histological inflammation was consistently defined. These results suggest that an absolute RST does not exist, and most RST cases consist of a relative RST [18, 19]. In addition, Park et al. [18]. reported that most RST patients develop remarkable, visible inflammation during disease progression. Therefore, we first excluded patients who received topical treatments from the RST group. Unfortunately, the initial degree of rectal inflammation, alteration and progression of the disease, and timing of RST appearance before surgery could not be evaluated retrospectively. However, RST diagnosed immediately before surgery was an independent risk factor for urgent/emergent surgery in this series. Urgent/emergent surgery may indicate refractoriness and resistance to pharmacotherapies. Oshitani et al. [15] reported that patients with endoscopically defined RST exhibited enhanced refractoriness and increased recurrence rates and had a longer duration of active disease than patients without the RST. Therefore, presence of the RST may predict a future colectomy.

Given the effects of several immunosuppressive therapies, associations between such therapies and the RST should be discussed. Almost all of the included patients received immunosuppressive treatment prior to surgery; however, their medical therapy failed, resulting in colectomy. It is difficult to envision that immunosuppressive treatment, with the exception of enema therapy, was effective in only the rectal segment. If immunosuppressive treatment had been effective, patients would have exhibited improved symptoms and would not have required surgery, and endoscopy would also have revealed remission in not only the rectum but also the entire colonic area.

Regarding the definition of the RST, we used surgical specimens or endoscopic findings from shortly before surgery to assess patients treated via colectomy alone. Although diagnosis of the RST was defined as relatively reduced or no inflammation of the rectum compared to proximal colitis, Joo and Odze [19] reported that all RST patients were classified as having a relative RST, which indicates the existence of histological inflammation, even to a mild degree. Additionally, those researchers observed no correlations between the endoscopic findings and the colectomy histological findings [19]. They concluded that absolute rectal sparing does not occur in UC, even after the long-term use of anti-inflammatory medications [19]. In this series, histological inflammation of the rectum was also defined in all RST patients; however, the inflammation was relatively mild compared to that of the proximal colon. We also conjecture that degrees of inflammation may be difficult to classify via histological findings alone or that most such findings may be classified as indicative of inflamed mucosa. Therefore, we considered the diagnosis and definition of RST as adequate, despite the limitations mentioned below.

Some limitations were present in this study. First, this was a retrospective study with small number of patients from a single center. Multicenter and prospective cohort studies are needed. Second, the indications for urgent surgery were slightly vague. The selection and duration of conservative treatments for refractory disease before surgery, the timing of urgent surgery, or the decision to perform surgery may differ among patients, institutions, physicians, or surgeons. Third, although we believe that our definition was adequate, the definition of the RST was slightly vague. The distinction was often difficult and might be inappropriate in patients with boundary findings between 0 and 1 for the Mayo endoscopic score. The distinction of resected surgical specimens might also be inappropriate, given that the conditions were defined based on the subjective impression of surgeons and histologists.

Our results suggest that a shorter duration of colitis, a low dose of total PSL, a high dose of pre-operative PSL, severe disease, and the RST are risk factors for urgent/emergent surgery. These results may reveal a lack of response to pharmacotherapies for treatment of the RST, or these patients may develop more extensive and rapid unresponsiveness to pharmacotherapies. Therefore, we should be aware that patients with an initial onset of UC whose colitis exhibits the RST and worsens within a short period may have a higher risk for further surgical intervention.

The RST of UC was an independent risk factor for urgent/emergent surgery based on an analysis of surgically treated UC patients. Although the developmental mechanism and clinical significance of the RST remain unclear, these findings may suggest the need for a future colectomy, disease refractoriness, and pharmacotherapy resistance.