How Useful Are Blood and Stool Biomarkers for Detecting Subclinical Mucosal Inflammation in Ulcerative Colitis?

Abstract

Endoscopy is essential for correct diagnosis and evaluation of the disease activity of ulcerative colitis (UC). Although the clinical symptoms of UC, for example mucoid diarrhea, bleeding, and abdominal pain can improve after appropriate therapy for active UC, inflammatory lesions can still be observed even in clinical remission. Stated differently, in a substantial number of cases, clinical symptoms and endoscopic lesions do not correlate. Furthermore, as the concept of endoscopic mucosal healing (MH) as a therapeutic target of inflammatory bowel disease gains acceptance, objective evaluation of inflammation is being increasingly emphasized. In contrast with Crohn’s disease (CD), which can involve the entire gastrointestinal tract, mucosal lesions of UC can more easily be evaluated endoscopically, because the inflammation is limited to the colon or rectum. Therefore, MH seems to be a more realistic therapeutic target in UC than in CD. Nevertheless, considering the discomfort of patients, the high cost of examination, and the potential complications of invasive procedures, well-validated surrogate markers for endoscopic lesions are needed. Although C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are nonspecific biomarkers of inflammation, they can be readily measured, serving as potential markers for mucosal inflammation in UC. Since mucosal hyperemia and granularity were used for endoscopic classification of UC patients in a pivotal study by Truelove et al. [1], several endoscopic scoring systems have been adopted in clinical research and practice. A decade after Truelove’s study was published, the Baron Score was developed in 1964. Soon after, the Powell–Tuck Score, the Mayo Endoscopic Score, the Rachmilewitz Endoscopic Index, Hanauer’s Sigmoidoscopic Index, and the modified Baron Score were introduced. Several studies have investigated the correlation of blood biomarkers and these endoscopic indices. In 2008, Osada et al. [2] scored the endoscopic activity in seven colonic segments (appendiceal region, cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum) by use of the Mayo Endoscopic Score, comparing endoscopic activity with blood biomarkers. They reported that CRP and ESR correlated well with proximal rather than distal colonic activity, suggesting that total colonoscopy is needed in cases of elevated CRP or ESR among UC patients in clinical remission [2]. Karoui et al. [3] also reported a significant correlation between CRP and the Rachmilewitz Endoscopic Index (r = 0.46, P 0.0001) in a prospective study of 101 UC patients. In a population-based study (the Inflammatory Bowel South-Eastern Norway II) of 61 newly diagnosed UC patients, the difference in CRP was significant between a Mayo Endoscopic Score of 1 and a Score of 3 (P = 0.007), and between Score 1 and a combination of Scores 2 and 3 (P = 0.016) [4]. Nevertheless, no prior studies have evaluated the correlation of blood biomarkers and the various endoscopic scoring systems at the same time. In this issue of Digestive Diseases and Sciences, Yoon et al. [5] investigated the correlation between blood inflammatory markers and endoscopic severity indices among patients with UC. They evaluated over 700 endoscopies, using five widelyused endoscopic scoring systems: the Powell–Tuck Score, the Mayo Endoscopic Score, the Rachmilewitz Endoscopic Index, Hanauer’s Sigmoidoscopic Index, and the modified B. D. Ye (&) Department of Gastroenterology and Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Republic of Korea e-mail: bdye@amc.seoul.kr