Mucosal Healing in Inflammatory Bowel Diseases
Mucosal Healing in Inflammatory Bowel Diseases
The course of inflammatory bowel diseases is heterogeneous and varies over time. Therefore, the search for predictive factors has increasingly become the focus of research. Mucosal healing has emerged as an important objective, as evidence indicates that it is associated with improved disease outcome. Nevertheless, many unsolved questions remain, including the definition of complete or partial healing as well as the best assessment method using endoscopic or imaging techniques, most of which are relatively invasive and expensive procedures, which therefore are not ideal for frequent monitoring and it is not clear. This review summarizes the available evidence in order to assist clinicians when assessing the mucosal status in the everyday practice.
Inflammatory bowel disease (IBD) includes Crohn's disease (CD) and ulcerative colitis (UC), chronic inflammatory diseases of the gut. Both are gastrointestinal diseases that may cause systemic signs. IBD causes diarrhea in most cases, with melena, hematochezia and passage of mucus alone or with stool. Symptoms may include abdominal pain, the location of abdominal pain depends on disease localization and severity. Weight loss, fever and extraintestinal manifestations (EIM), such as erythematous or ulcerous cutaneous changes, arthropathies and concomitant liver diseases may appear in both UC and CD.
Despite the similarities in the clinical manifestations of these conditions, there are distinct differences between CD and UC. UC is essentially a colonic disease, with pathologic changes starting near the anus and extending ad oral in the large bowel, whereas CD causes discrete lesions which may manifest anywhere along the gut from the mouth to the anus.
IBD also differ in histological predilection; UC primarily affects the mucosal layer whereas CD penetrates more deeply. Despite this difference, endoscopic examination of the colon and terminal ileum remains an essential factor for the diagnosis of both diseases (including clinical, microbiological (negative), radiologic, endoscopic and histologic criteria), even in transmural CD. Endoscopy is also used to evaluate the efficacy of therapeutic interventions. Nevertheless, there is debate regarding the short- and long-term prognostic value of even endoscopically verified mucosal healing (MH).
Both types of IBD are progressive and relapsing. The consequences of relapses are often cumulative, leading to irreversible intestinal damage, despite even long periods of remission. Due to its transmural nature, intra-enteral adhesions, enteroenteric and enterovisceral fistulas and abscesses are common in CD – and all of these may require surgical intervention. Perianal involvement may occur as the first symptom of CD, or can represent a late complication of the disease. Similarly, in UC, mucosal atrophy and pseudopolyp formation are common in patients with a prolonged disease history. The colon can be shortened in these cases. Colorectal cancer is a relatively rare but severe complication of UC, as is concomitant primary sclerosing cholangitis. In addition to the debilitating bowel complications of IBD, EIM may also cause irreversible organ damage. Ankylosing spondylitis may progress to the point where movement of the spine is severely restricted, while concomitant liver diseases often progress to cirrhosis and liver failure.
As the sequelae of IBD are usually progressive resulting in significant disability, current therapeutic approaches aim to prevent or reduce complications. To reach these therapeutic goals, earlier use of a variety of agents, including anti-TNF-α drugs, immunosuppressants (azathioprine [AZA], methotrexate [MTX], and so on) has been employed. Considering the potentially severe adverse events and high costs of these drugs, however, it is desirable to predict the disease course of individual patients. Potential prognostic factors, including genetic and clinical markers, were evaluated widely in the last decade. Traditionally, symptomatic improvement was the primary goal, with little attention given to cumulative gastrointestinal damage, a concept introduced by Marc Lemann. Recently, MH became the subject of focus, since it was found to be associated with short- and long-term outcomes in both types of IBD. For example, Baert et al. report that complete endoscopic remission predicts sustained corticosteroid-free clinical remission in early-stage CD patients.
It is still uncertain whether MH better predicts cumulative intestinal damage compared with clinical measures. Results are somewhat controversial, possibly partly due to the difference in study design and definitions used. The core question remains the same: is MH associated with better disease course, including short-, long-term outcomes? If the answer is yes, this would significantly affect patient management; instead of symptom control and 'clinical' remission, the preferred goal would be MH. Thus, MH would be integral to the definition of remission, as was recently suggested by Panaccione et al. In this review article, the authors summarize the available literature on the importance of MH in IBD and discuss uncertainties around its definition, MH rates and the association with short- and long-term outcomes.
Abstract and Introduction
Abstract
The course of inflammatory bowel diseases is heterogeneous and varies over time. Therefore, the search for predictive factors has increasingly become the focus of research. Mucosal healing has emerged as an important objective, as evidence indicates that it is associated with improved disease outcome. Nevertheless, many unsolved questions remain, including the definition of complete or partial healing as well as the best assessment method using endoscopic or imaging techniques, most of which are relatively invasive and expensive procedures, which therefore are not ideal for frequent monitoring and it is not clear. This review summarizes the available evidence in order to assist clinicians when assessing the mucosal status in the everyday practice.
Introduction
Inflammatory bowel disease (IBD) includes Crohn's disease (CD) and ulcerative colitis (UC), chronic inflammatory diseases of the gut. Both are gastrointestinal diseases that may cause systemic signs. IBD causes diarrhea in most cases, with melena, hematochezia and passage of mucus alone or with stool. Symptoms may include abdominal pain, the location of abdominal pain depends on disease localization and severity. Weight loss, fever and extraintestinal manifestations (EIM), such as erythematous or ulcerous cutaneous changes, arthropathies and concomitant liver diseases may appear in both UC and CD.
Despite the similarities in the clinical manifestations of these conditions, there are distinct differences between CD and UC. UC is essentially a colonic disease, with pathologic changes starting near the anus and extending ad oral in the large bowel, whereas CD causes discrete lesions which may manifest anywhere along the gut from the mouth to the anus.
IBD also differ in histological predilection; UC primarily affects the mucosal layer whereas CD penetrates more deeply. Despite this difference, endoscopic examination of the colon and terminal ileum remains an essential factor for the diagnosis of both diseases (including clinical, microbiological (negative), radiologic, endoscopic and histologic criteria), even in transmural CD. Endoscopy is also used to evaluate the efficacy of therapeutic interventions. Nevertheless, there is debate regarding the short- and long-term prognostic value of even endoscopically verified mucosal healing (MH).
Both types of IBD are progressive and relapsing. The consequences of relapses are often cumulative, leading to irreversible intestinal damage, despite even long periods of remission. Due to its transmural nature, intra-enteral adhesions, enteroenteric and enterovisceral fistulas and abscesses are common in CD – and all of these may require surgical intervention. Perianal involvement may occur as the first symptom of CD, or can represent a late complication of the disease. Similarly, in UC, mucosal atrophy and pseudopolyp formation are common in patients with a prolonged disease history. The colon can be shortened in these cases. Colorectal cancer is a relatively rare but severe complication of UC, as is concomitant primary sclerosing cholangitis. In addition to the debilitating bowel complications of IBD, EIM may also cause irreversible organ damage. Ankylosing spondylitis may progress to the point where movement of the spine is severely restricted, while concomitant liver diseases often progress to cirrhosis and liver failure.
As the sequelae of IBD are usually progressive resulting in significant disability, current therapeutic approaches aim to prevent or reduce complications. To reach these therapeutic goals, earlier use of a variety of agents, including anti-TNF-α drugs, immunosuppressants (azathioprine [AZA], methotrexate [MTX], and so on) has been employed. Considering the potentially severe adverse events and high costs of these drugs, however, it is desirable to predict the disease course of individual patients. Potential prognostic factors, including genetic and clinical markers, were evaluated widely in the last decade. Traditionally, symptomatic improvement was the primary goal, with little attention given to cumulative gastrointestinal damage, a concept introduced by Marc Lemann. Recently, MH became the subject of focus, since it was found to be associated with short- and long-term outcomes in both types of IBD. For example, Baert et al. report that complete endoscopic remission predicts sustained corticosteroid-free clinical remission in early-stage CD patients.
It is still uncertain whether MH better predicts cumulative intestinal damage compared with clinical measures. Results are somewhat controversial, possibly partly due to the difference in study design and definitions used. The core question remains the same: is MH associated with better disease course, including short-, long-term outcomes? If the answer is yes, this would significantly affect patient management; instead of symptom control and 'clinical' remission, the preferred goal would be MH. Thus, MH would be integral to the definition of remission, as was recently suggested by Panaccione et al. In this review article, the authors summarize the available literature on the importance of MH in IBD and discuss uncertainties around its definition, MH rates and the association with short- and long-term outcomes.
Source...