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Calprotectin

Calprotectin is a zinc and calcium binding protein that is released from neutrophils and monocytes into body fluids and stool. Fecal calprotectin is an indicator of the presence of neutrophils in stool. The concentration of calprotectin is directly proportional to the intensity of neutrophilic infiltration in the gastrointestinal mucosa. Fecal calprotectin is increased in patients with inflammatory bowel disease such as ulcerative colitis and Crohn’s disease. Calprotectin levels are generally higher in patients with inflammatory bowel disease than irritable bowel syndrome.

Patients with irritable bowel syndrome and inflammatory bowel disease share many of the same clinical symptoms. Numerous studies have looked at the diagnostic utility of using calprotectin to distinguish between inflammatory bowel disease and other GI disorders. Many studies have shown that calprotectin has a sensitivity of greater than 90% for the diagnosis of inflammatory bowel disease, but has much lower specificity, ranging from 60 to 90%. The high sensitivity of fecal calprotectin suggests that a low fecal concentration of less than 50 ug per gram of stool can be used to rule out inflammatory bowel disease.

The lower specificity means that an elevated fecal calprotectin result cannot be used by itself to diagnose inflammatory bowel disease. Increased calprotectin is not specific for inflammatory bowel disease. Fecal calprotectin may be increased in bacterial or viral gastroenteritis, food intolerance, nonsteroidal enteropathy, colorectal cancer and after pelvic irradiation. Colonoscopy is usually required to confirm the diagnosis of inflammatory bowel disease.

An algorithm using calprotectin has been proposed to decrease the number of colonoscopies. The algorithm begins with measuring fecal calprotectin in a patient who has symptoms consistent with inflammatory bowel disease. A fecal calprotectin result less than 50 ug per gram indicates a noninflammatory condition such as irritable bowel syndrome, while a result greater than 150 ug per gram is consistent with an inflammatory GI disease. Further evaluation with endoscopy or colonoscopy may be necessary to confirm inflammatory bowel disease in patients with elevated fecal calprotectin. Patients with indeterminate results between 50 and 150 ug per gram are recommended to have their calprotectin level repeated in two weeks after ruling out other causes of inflammation such as nonsteroidal anti-inflammatory drug use. If calprotectin is still greater than 50 ug per gram, then colonoscopy might be indicated. If calprotectin is below 50 ug per gram, irritable bowel syndrome is more likely.  Prior testing with fecal calprotectin may result in a 50% reduction in the number of adults and 70% reduction in the number of children requiring colonoscopy.

Calprotectin levels cannot distinguish between ulcerative colitis and Crohn's disease. Patients with inflammatory bowel disease alternate between active and inactive stages of disease. Calprotectin results may also fluctuate during these stages. Serial calprotectin levels can be used to monitor response to infliximab or adalimumab therapy, but no cutoff has been established for clinical remission. Calprotectin may remain elevated in some patients in clinical remission, suggesting the presence of subclinical mucosal inflammation. Elevation of calprotectin after discontinuation of therapy is a risk factor for relapse. GI bleeding of as much as 100 mL per day increases fecal calprotectin concentration by 15 µg/g.

Fecal calprotectin is measured with an enzyme linked immunosorbent asay (ELISA). Reference range is <50 ug calprotectin per gram of stool.  Depending on the ELISA, results greater than 150 ug per gram are suggestive of inflammatory bowel disease.  Indeterminate levels between 50 and 150 µg per gram should be repeated in 4 to 6 weeks. Considerable intra-individual day to day variability of fecal calprotectin may exist.

Specimen requirement is 5 grams of random stool in a screw-capped, plastic container. Calprotectin is homogenously distributed within a stool specimen. Calprotectin is stable in feces for up to 7 days at room temperature. No preservative is necessary.

Other stool tests for inflammation include fecal leukocytes and lactoferrin.

Lehmann FS, et al, The role and utility of faecal markers in inflammatory bowel disease. Ther Adv Gastroenterol. 2015;8(1)23-36. 

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