Assessing the presence, severity, and extent of intestinal inflammation is an essential component in the workup of patients with common digestive complaints such as abdominal pain and cramping, bowel movement disturbances, bloating, and flatulence. It also is indicated for complaints such as fever, weight loss, and fatigue, which are often associated with inflammatory bowel disease (IBD) or other inflammatory intestinal disorders.
Because intestinal inflammation is not directly observable by patients or clinicians, laboratory assays provide critical information to help determine the presence, location, and magnitude of such inflammation. Laboratory stool analysis is the most convenient and noninvasive means of assessing inflammation in the intestinal tract. Elevated stool inflammatory biomarkers point to an active process of intestinal mucosal cell damage. Such damage may be associated with a variety of causes, including acute or chronic intestinal infection (viral, bacterial or parasitic), IBD, diverticulitis, celiac disease, food allergy, NSAID-induced enteropathy, and colorectal cancer.
DiagnosTechs has offered stool markers of intestinal inflammation for some time, and we also now offer a test for fecal calprotectin. Calprotectin is an abundant neutrophil protein, and its presence in stool is indicative of neutrophilic infiltration into the gut lumen associated with inflammation. Elevated concentrations of fecal calprotectin have been found in patients with infectious and inflammatory conditions, including IBD.1
A key problem in gastroenterology is the clinical differentiation of IBD and irritable bowel syndrome (IBS). Many patients in the IBS category are still routinely investigated with extensive and invasive imaging studies to rule out IBD. Because IBS is a functional disorder, the absence of biomarkers of intestinal inflammation such as fecal calprotectin can point toward an IBS diagnosis. In most patients presenting with common intestinal symptoms, a normal fecal calprotectin can help clinicians rule out active IBD without the need for colonoscopy. In a study of 600 patients referred to a gastroenterology clinic with symptoms suggestive of either IBS or inflammatory intestinal disease, the sensitivity and specificity of calprotectin for predicting inflammatory disease were 89% and 79%, respectively.2 Meta-analysis of multiple similar studies involving nearly 6000 patients demonstrates even greater test sensitivity and specificity. As a diagnostic test overall, fecal calprotectin shows a 95% sensitivity and 91% specificity for identifying IBD patients.3 Assessing fecal calprotectin first can help clinicians identify patients with abdominal symptoms who are likely to benefit from more invasive diagnostic procedures.
IBD, which includes Crohn’s disease and ulcerative colitis, is marked by chronic, recurrent episodes of inflammation in the gastrointestinal tract. Because levels of inflammation reflect severity of the disease process, detection and monitoring are key to clinical management. Fecal calprotectin can aid in this detection, as well as provide a noninvasive means to track disease activity, risk of relapse, and response to treatment. Fecal calprotectin values have been shown to correlate with endoscopic and histological assessment of disease activity in IBD patients.1 Levels of fecal calprotectin also correlate well with radio-labeled leukocyte scanning, a costly and invasive procedure formerly used to assess active intestinal inflammation in Crohn’s disease.4 Overall, fecal calprotectin strongly outperforms serum C-reactive protein (CRP) and other inflammatory markers in assessing IBD treatment efficacy and in predicting disease relapse.5
Fecal calprotectin is not specific for IBD but rather indicates inflammatory cell shedding into the gut lumen. Calprotectin levels therefore may be elevated in a variety of inflammatory conditions including certain cases of celiac disease, food allergy, infectious diarrhea, diverticulitis, NSAID-induced enteropathy, and some gastrointestinal malignancies. A positive fecal calprotectin test should be evaluated in the context of the patient’s clinical presentation, and likely will warrant further testing.
It is not yet clear whether calprotectin might be useful in the diagnosis or management of celiac disease. A study of 29 children newly diagnosed with celiac disease (in its classic presentation including failure to thrive) found significantly elevated fecal calprotectin levels in patients relative to matched controls. In these patients calprotectin levels correlated with the severity of histopathologic findings at diagnosis. After one year on a gluten-free diet, calprotectin levels in these patients returned to levels found in healthy controls.6 Another small study of children with celiac disease, evaluating both untreated (n=31) and treated (n=33) participants, noted similar findings.7
By contrast, fecal calprotectin levels in untreated adult celiac disease patients have been shown to be normal (no different from healthy controls) or only inconsistently elevated. In particular, a small study of 28 adults with biopsy-confirmed, untreated celiac disease and matched healthy controls found no significant difference in fecal calprotectin levels.8 Another study of 120 adult and pediatric patients with chronic diarrhea found that calprotectin was reliable in identifying patients with IBD, but not as consistent at distinguishing patients with celiac disease from those with IBS. In this prospective study, fecal calprotectin levels in patients diagnosed with celiac disease were elevated in only 5 out of 10 adult patients and 7 out of 13 pediatric patients, with the remaining celiac disease patients having normal values.9 In summary, certain pediatric celiac disease patients may show elevated levels of fecal calprotectin that decline with treatment, yet others may have normal values even before treatment. Some untreated adult celiac disease patients may have elevated calprotectin, although most will likely show normal results. Calprotectin is not currently recommended for diagnosis or monitoring in celiac disease.
For patients with persistent digestive complaints in general, fecal calprotectin serves as a convenient and noninvasive marker of intestinal mucosal inflammation. In all cases, an elevated calprotectin test should prompt consideration of further testing to determine the specific cause of the inflammation, such as stool testing for microbial pathogens, food allergy testing, dietary elimination and challenge trial, serum antibody testing for celiac disease followed by endoscopy when indicated, and colonoscopy to assess for organic pathologies including inflammatory bowel disease and colon cancer.
In addition to the fecal calprotectin test, DiagnosTechs will continue to offer our other stool markers of intestinal inflammation—lysozyme and alpha 1-antichymotrypsin—in addition to related markers of total intestinal secretory IgA (sIgA) and fecal occult blood. Together with the fecal calprotectin test, these markers will help clinicians to quantify intestinal inflammation, differentiate inflammatory from functional causes of intestinal disturbance, and obtain a glimpse into intestinal mucosal immune function and epithelial integrity.
Fecal calprotectin can be ordered as a stand-alone test or as an addition to our regular GI Health Panel or Expanded GI Health Panel. Providers may login and order directly online.
This article has been updated from ChronoBiology 16.
References
- Konikoff MR, Denson LA. Role of fecal calprotectin as a biomarker of intestinal inflammation in inflammatory bowel disease. Inflamm Bowel Dis. 2006; 12(6):524-534.
- Tibble JA, Sigthorsson G, Foster R, Forgacs I, Bjarnason I. Use of surrogate markers of inflammation and Rome criteria to distinguish organic from nonorganic intestinal disease. Gastroenterology. 2002;123(2):450-60.
- von Roon AC, Karamountzos L, Purkayastha S, et al. Diagnostic precision of fecal calprotectin for inflammatory bowel disease and colorectal malignancy. Am J Gastroenterol. 2007;102(4):803-13.
- Røseth AG, Schmidt PN, Fagerhol MK. Correlation between faecal excretion of indium-111-labelled granulocytes and calprotectin, a granulocyte marker protein, in patients with inflammatory bowel disease. Scand J Gastroenterol. 1999;34(1):50-4.
- Lewis JD. The utility of biomarkers in the diagnosis and therapy of inflammatory bowel disease. Gastroenterology. 2011;140(6):1817-1826.
- Ertekin V, Selimoğlu MA, Turgut A, Bakan N. Fecal calprotectin concentration in celiac disease. J Clin Gastroenterol. 2010;44(8):544-6.
- Balamtekın N, Baysoy G, Uslu N, et al. Fecal calprotectin concentration is increased in children with celiac disease: relation with histopathological findings. Turk J Gastroenterol. 2012;23(5):503-8.
- Montalto M, Santoro L, Curigliano V, et al. Faecal calprotectin concentrations in untreated coeliac patients. Scand J Gastroenterol. 2007;42(8):957-61.
- Carroccio A, Iacono G, Cottone M, et al. Diagnostic accuracy of fecal calprotectin assay in distinguishing organic causes of chronic diarrhea from irritable bowel syndrome: a prospective study in adults and children. Clin Chem. 2003;49(6 Pt 1):861-7.