The therapeutic goal for treating ulcerative colitis (UC) patients has shifted to achieving mucosal healing over the past few years. However, at present, limited data is available on the correlation between endoscopic findings and histological remission in patients with endoscopic mucosal healing.
This was a prospective observational study conducted over a period of 18 months (January 2014 to June 2015) at Dayanand Medical College and Hospital, Ludhiana, Punjab, India. Patients diagnosed with UC who had been in clinical remission (n=76) for at least 6 months were evaluated for endoscopic remission. Those in endoscopic remission (Mayo score ≤1; 46/76, 60.5%) were subjected to multiple biopsies from the rectosigmoid region and histological remission, which was then defined as grade 0/1 as per the Geboes criteria.
Of the 46 patients in endoscopic remission (age, 18–73 years; male:female=1.5:1.0), majority had E1 (proctitis) disease (21/46, 45.6%) followed by E2 (left sided colitis) (18/46, 39.1%) and E3 disease (pancolitis) (7/46, 15.2%) at baseline. Histological remission was noted in 67.3% (31/46) of the patients, while 32.7% (15/46) still retained the histologically active disease in the form of infiltration of the lamina propria by eosinophils and neutrophils (13/15, 86.6%), cryptitis (14/15, 93.3%), and crypt abscesses (8/15, 53.3%). On follow-up, after 1 year, 87.1% (27/31) of the patients who had been in histological remission remained clinically asymptomatic, while 12.9% (4/31) had relapsed. Among the 15 histologically active patients, 46.6% (7/15) remained in clinical remission, while 53.3% (8/15) had relapsed.
Histological remission, rather than endoscopic remission, predicts a sustained clinical remission and allows monitoring of therapy for the subsequent disease course in patients with UC.
Ulcerative colitis (UC) is a chronic IBD with a relapsing and remitting course. The optimal goal of treatment of IBD is the complete resolution of the inflammatory process, and this is achieved only when patients in clinical remission have a corresponding mucosal healing. Mucosal healing may be observed on both endoscopic and histological aspects, and at present a standardized definition of mucosal healing for IBD patients does not exist. Although most studies on mucosal healing focus on endoscopic scores, some experts have suggested histological inflammation is a better predictor of future clinical relapse than endoscopic appearance alone.
This was a prospective, observational study assessing the association between the histological remission and long-term clinical course in patients with UC, conducted in the Departments of Gastroenterology and Pathology, Dayanand Medical College and Hospital, Ludhiana, between January 2014 to June 2015 (18 months) and subsequently followed up for 1 year.
The diagnosis of UC was based on accepted clinical, endoscopic, and histological criteria. Clinical remission was defined as a Simple Clinical Colitis Activity Index ≤2 for at least 6 months and endoscopic remission (normal with clearly visible vascular pattern or erythema with decreased vascular pattern but no bleeding, i.e., Mayo score ≤1). Patients with active disease on endoscopy (Mayo ≥2) were excluded.
Patients who were in clinical remission (n=76) for at least 6 months were subjected to ileocolonoscopy. Patients who were in endoscopic remission (46/76, 60.5%) were subjected to 4 biopsies from the rectosigmoid region to evaluate histological activity. As per Geboes criteria (2000), grade 0/1 was defined as histological remission.
The patients showing endoscopic remission were maintained on a stable dose of mesalamine and azathioprine/6-mercaptoprine and were followed up for 1 year to observe the clinical course. Patients on steroids, biological therapies, rectal mesalamine, or steroid enemas were not included in the present study.
The data collected were subjected to statistical analysis. Mean and standard deviation were computed and paired
Seventy-six patients had a sustained clinical remission during 2014 to 2015, the duration of which ranged from 6 months to >5 years. Of these 76 patients, 46 were in endoscopic remission (age, 18–73 years; male:female=1.5:1.0). Prior to starting treatment, these patients had E1 disease (proctitis) in 45.6% (21/46) followed by E2 (left sided colitis; 18/46, 39.1%) and E3 (extensive colitis; 7/46, 15.2%) disease. According to the average duration of remission at the time of analysis, the patients were grouped as follows: 6 months to <2 years (38/46, 82.6%), 2 to 5 years (6/46, 13.0%), and >5 years (2/46, 4.3%) (
The patients in endoscopic remission were subjected to endoscopic biopsies from the rectosigmoid region. Histological remission was noted in 67.3% of patients (31/46), while 15 (32.7%) patients still had histologically active disease in the form of infiltration of the lamina propria by eosinophils and neutrophils (13/15, 86.6%), cryptitis (14/15, 93.3%), and crypt abscesses (8/15, 53.3%) (
When followed up for 1 year, nearly twice the number of patients in histological remission remained in clinical remission when compared with those with histological activity (87.1% vs. 46.6%, respectively,
Although the concept of “deep remission” has developed in CD, it has not been replicated in those with UC. Most studies on mucosal healing focus on endoscopic scores, and the data from various trials suggests that patients with Mayo score 0 (complete mucosal healing) have longer-lasting remissions. However, patients with UC who are in clinical and endoscopic remission may still have histologically active disease and are at a high risk of having a relapse,
Of the 46 patients who were in endoscopic remission in our study, 67.3% patients (31/46) were in histological remission, but 32.6% (15/46) still had histologically active disease. When the long-term clinical outcomes were assessed after 1 year, the rate of a sustained clinical remission was significantly higher in patients who attained histological remission than among those who showed signs of active inflammation on histopathology (87.1% vs. 46.6%,
When patients with endoscopically quiescent disease are subjected to biopsy, the histopathology may show features that suggest disease activity. These include the presence of neutrophilic infiltrates in the lamina propria, epithelial cell damage (loss of cells, mucin depletion, cryptitis, crypt abscesses, and erosion), and an increase in lymphocytes and plasma cells. The presence of neutrophils is a reliable indicator of disease activity, with a good inter-observer agreement in various studies. Histology may also predict relapse or dysplasia. Histological findings predictive of ensuing clinical relapse in patients with quiescent disease are the persistence of neutrophils, basal plasmacytosis, mildly active disease, and an elevated number of eosinophils.
In our study, more than 70% of patients in endoscopic remission showed mild crypt distortion and mild to moderate increases in chronic inflammatory cells in the lamina propria. The presence of eosinophils and neutrophils in the lamina propria, cryptitis, and crypt abscesses were seen only in the histologically active group. Thus, the presence of acute inflammatory infiltrates and crypt destruction were predictors of activity and relapse. These findings are consistent with other studies.
In a multivariate analysis of data from 74 patients with inactive UC, relapse was also predicted by the presence of basal plasmacytosis.
Factors such as age, gender, extent of disease, and duration of clinical remission were not found to be statistically significant in predicting relapse. We attribute this to the smaller number of patients in the analysis. A limitation of our study is that we did not analyze any of the available biological parameters but during our previous analysis these were not statistically significant.
Though achievement of histological healing provides a more accurate picture of recovery and improves the disease outcomes, it seems to be a relatively difficult goal to achieve. In addition to this, there are certain unresolved issues. Most of the scoring systems for endoscopy and histological features are either not validated or only partially validated.
Thus, in conclusion, histological remission and healing serves as a better marker of treatment efficacy in patients with UC and is a better predictor of sustained remission in patients than endoscopic remission. Histologic remission and healing is an area of increased research focus and has the promise of being an important marker of treatment efficacy in UC, with the potential to guide treatment decisions in the future.
In conclusion, mucosal healing is associated with better clinical outcomes in patients with UC; however, histologic parameters may provide a more accurate picture of the recovery of the mucosa and further improve disease outcomes. This study indicates that histologic healing may be associated with better outcomes in UC thus providing a rationale for making this a treatment goal. The present analysis is small but is a progressive step towards better defining remission in UC.
Values are presented as number (%).
MES, mayo endoscpoic subscore.
MES, mayo endoscopic subscore.