Role of Fecal Calprotectin as a Biomarker of Intestinal Inflammation in Inflammatory Bowel Disease Michael R. Konikoff, MD and Lee A. Denson, MD Abstract: Calprotectin is an abundant neutrophil protein found in both plasma and stool that is markedly elevated in infectious and inflammatory conditions, including inflammatory bowel disease (IBD). We conducted a systematic review of the published literature regarding fecal calprotectin to evaluate its potential as a noninvasive marker of neutrophilic intestinal inflammation. Reference ranges for fecal calprotectin have been established in healthy adults and children, and elevated concentrations of fecal calprotectin have been demonstrated in numerous studies of patients with IBD. Fecal calprotectin correlates well with histological inflammation as detected by colonoscopy with biopsies and has been shown successfully to predict relapses and detect pouchitis in patients with IBD. Fecal calprotectin has been shown to consistently differentiate IBD from irritable bowel syndrome because it has excellent negative predictive value in ruling out IBD in undiagnosed, symptomatic patients. Fecal calprotectin also may be useful in determining whether clinical symptoms in patients with known IBD are caused by disease flares or noninflammatory complications/underlying irritable bowel syndrome and in providing objective evidence of response to treatment. Although more studies are needed to define fully the role of fecal calprotectin, convincing studies and growing clinical experience point to an expanded role in the diagnosis and management of IBD. Key Words: inflammatory bowel disease, calprotectin, biological markers, gastrointestinal diseases, feces/chemistry (Inflamm Bowel Dis 2006;12:524–534) I nflammatory bowel disease (IBD), which includes Crohn_s disease (CD) and ulcerative colitis (UC), is a chronic condition marked by recurrent episodes of inflammation in the gastrointestinal tract. This inflammation underlies many of the symptoms and signs of the disease; thus, its detection and monitoring are of utmost importance in clinical manage- ment. Because gastrointestinal inflammation is not directly observable by patients or physicians, many methods have been developed to quantify the severity and extent of this inflammation. Patient symptoms can be an important indicator of inflammation and disease activity but are subjective and may be influenced by other noninflammatory features of the disease such as intestinal strictures or bile salt malabsorption. Activity indexes such as the Crohn_s Disease Activity Index and the Harvey Bradshaw Index use a combination of symptoms, examination findings, and laboratory parameters to establish disease activity. These indexes have been rigorously developed and validated in clinical trials, 1Y3 but they are cumbersome to use in clinical practice and still rely heavily on subjective patient symptoms. Serological and hematological parameters are used widely to assess disease activity, but these systemic markers have low sensitivity and specificity for intestinal inflammation and correlate poorly with symptoms and disease activity indexes. 4,5 Imaging studies such as CT and MRI scans, barium enemas, and enteroclysis can be useful in localizing intestinal inflamma- tion, but these studies often are expensive, have suboptimal sensitivity and/or specificity, and may be invasive or expose the patient to ionizing radiation. The current gold standard for assessing intestinal inflammation is endoscopy with biopsies. This technique allows visual inspection of the gastrointestinal tract, and mucosal biopsy specimens can be obtained for histological examination. The location, extent, and severity of disease can be established with this procedure, but it is invasive, cannot examine the entire gastrointestinal tract, and requires both a skilled operator and an uncomfortable preparatory regimen. Wireless capsule endoscopy has now allowed visualization of the entire small bowel. However, this is somewhat invasive and is limited by its cost and the inability to obtain tissue samples. These limitations prevent frequent assessment of disease activity by endoscopic techniques. Thus, it is clear that a simple, rapid, sensitive, specific, inexpensive, non- invasive marker to detect and monitor intestinal inflammation in IBD is needed. Fecal calprotectin may possess these characteristics. Calprotectin is an abundant calcium-binding protein belonging to the S100 family that is derived predominantly CLINICAL REVIEW 524 Inflamm Bowel Dis & Volume 12, Number 6, June 2006 Received for publication October 31, 2005; accepted March 13, 2006. From the Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children_s Hospital Medical Center, Cincinnati, Ohio. Reprints: Lee A. Denson, MD, Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children_s Hospital Medical Center, 3333 Burnet Ave, MLC 2010, Cincinnati, OH 45229 (e-mail: Lee.Denson@cchmc.org) Copyright * 2006 by Lippincott Williams & Wilkins Copyr ight © Lippincott Williams & Wilkins. Unauthor iz ed reproduction of this article is prohibited.