A Critical Review of Persistent Gastrointestinal and Extraintestinal Symptoms in Quiescent Inflammatory Bowel Disease: Time for Greater Precision and Clarity

BACKGROUND AND AIMS: Despite improved therapies targeting inflammation in inflammatory bowel disease, persistent gastrointestinal and extraintestinal symptoms in those believed to be in remission are highly prevalent with significant impact on patient function and quality of life. This review aims to summarize the scale of the problem, to identify the limitations of previous studies, and to propose how these may be addressed. METHODS: The published literature was extensively reviewed. RESULTS: Persistent gastrointestinal symptoms are reported in up to 40% of patients with inflammatory bowel disease in apparent remission and have mostly been characterized using the Rome criteria, which are unvalidated in this population. They are also closely linked to anxiety/depression and fatigue. Importantly, studies have frequently failed to use tests with high negative predictive values to exclude intestinal inflammation and have assumed severe symptoms are inflammatory in nature. The presence of ongoing inflammation and different mechanisms underlying the development of symptom-generating abnormalities, including visceral hypersensitivity and central sensitization, that are shared by disorders of gut-brain interaction are evident in the small number of studies performed. Thus, the concept that inflammatory and noninflammatory symptoms are mutually exclusive may be fallacious. CONCLUSIONS: Persistent gastrointestinal symptoms are common in patients with inflammatory bowel disease in apparent remission, but variable criteria to define inflammatory remission may introduce a high risk of bias within existing literature. Further research using objective and robust measures of inflammatory remission is key to better defining this population and to clarifying pathophysiological mechanisms so that effective management strategies can be developed.