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DESCRIPTIONFecal calprotectin is a calcium- and zinc-binding protein that is a potential marker of intestinal inflammation. Fecal calprotectin testing is proposed as a noninvasive test to diagnose inflammatory bowel disease (IBD). Other potential uses are to evaluate response to treatment for patients with IBD and as a marker of relapse.
Inflammatory bowel disease (IBD) is a chronic inflammatory condition typically associated with the symptoms of diarrhea, defecation urgency, and sometimes rectal bleeding and abdominal pain. There are two main forms of the disorder, Crohn’s disease (CD) and ulcerative colitis (UC). Noninvasive diagnosis of inflammatory intestinal disease is difficult because the clinical manifestation of intestinal disorders and colon cancer are relatively non-specific. For example, a patient presenting with diarrhea or abdominal pain has a wide range of diagnostic possibilities. Endoscopy with histology is the criterion standard method for diagnosing bowel inflammation. Limitations of this approach are that it is invasive, with an associated risk of adverse events, and not well-tolerated by some patients.
There is, thus, the need for simple, accurate, noninvasive tests to detect intestinal inflammation. Potential noninvasive markers of inflammation fall into several categories, including serological and fecal. Serologic markers such as C-reactive protein and anti-neutrophil cytoplasmic antibodies tend to have low sensitivity and specificity for intestinal inflammation because they are affected by inflammation outside of the gastrointestinal tract. Fecal markers, in contrast, have the potential for being more specific to the diagnosis of gastrointestinal tract disorders since their levels are not elevated in extra-digestive processes. Fecal leukocyte testing has been used to evaluate whether there is intestinal mucosal inflammation. The level of fecal leukocytes can be determined by the microscopic examination of fecal specimens; however, leukocytes are unstable and must be evaluated promptly by skilled personnel. There is interest in identifying stable proteins in stool specimens, which may be representative of the presence of leukocytes, rather than evaluating leukocyte levels directly.
Fecal calprotectin is one protein that could possibly be used as a marker of inflammation. It is a calcium- and zinc-binding protein that accounts for about 60% of the neutrophils’ cytoplasmic proteins. It is released from neutrophils during activation or apoptosis/necrosis and has a role in regulating inflammatory processes. In addition to potentially higher sensitivity and specificity than serologic markers, a potential advantage of fecal calprotectin as a marker is that it has been shown to be stable in feces at room temperature for up to a week, leaving enough time for patients to collect samples at home and send them to a distant laboratory for testing. In contrast, lactoferrin, another potential fecal marker of intestinal inflammation, is stable at room temperature for only about 2 days.
Among potential disadvantages of fecal calprotectin as a marker of inflammation are that fecal calprotectin levels increase after use of non-steroidal anti-inflammatory drugs, that levels may change with age, and that bleeding (e.g., nasal or menstrual) may cause an elevated fecal calprotectin level. Moreover, there is uncertainty about the optimal cutoff to use to distinguish between inflammatory bowel disease and non-inflammatory disease.
Fecal calprotectin testing has been used to distinguish between organic and functional intestinal disease. Some authors consider fecal calprotectin to be a marker of neutrophilic intestinal inflammation rather than a marker of organic disease and believe the appropriate use of the marker is to use it to distinguish between inflammatory bowel disease and non-inflammatory bowel disease. In practice, the test might be suitable for selecting patients with IBD symptoms for endoscopy, i.e. deciding which patients do not require endoscopy. Fecal calprotectin testing has also been proposed to evaluate the response to IBD treatment and for predicting relapse. If found to be sufficiently accurate, results of calprotectin testing could potentially be used to change treatment, such as adjusting medication levels.
There is a commercially available enzyme-linked immunosorbent assay (ELISA) test measuring fecal calprotectin levels, the PhiCal™ (Genova Diagnostics). Recent literature from Europe has also discussed a rapid test for fecal calprotectin that could be used in the home or doctor's office. At least one product, the Bühlmann Quantum Blue® Calprotectin Rapid Test, is being marketed outside of the United States; rapid tests have not been FDA-approved for use in the United States.
In March 2006, the PhiCal™ (Genova Diagnostics) quantitative ELISA test for measuring concentrations of fecal calprotectin in fecal stool was cleared for marketing by the Food and Drug Administration (FDA) through the 510(k) process. This test is indicated to aid in the diagnosis of inflammatory bowel disease and to differentiate IBD from irritable bowel syndrome (IBS); it is intended for use with other diagnostic testing and clinical considerations.
In January 2014, CalPrest® (Eurospital SpA) was cleared for marketing by FDA through the 510(k) process. According to the FDA summary, CalPrest “is identical” to the PhiCal™ test “in that they are manufactured by Eurospital S.p.A. Trieste, Italy. The only differences are the name of the test on the labels, the number of calibrators in the kit and the dynamic range of the assay.”
Fecal Analysis in the Diagnosis of Intestinal Dysbiosis is a related medical policy.
POLICYFecal calprotectin testing is considered investigational in the diagnosis and management of intestinal conditions, including the diagnosis and management of inflammatory bowel disease.
POLICY GUIDELINESInvestigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.
The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.
POLICY HISTORY07/29/2011: Approved by Medical Policy Advisory Committee.
05/09/2012: Policy reviewed; no changes.
08/07/2013: Policy reviewed; no changes.
07/11/2014: Policy reviewed; no changes.
09/15/2014: Policy reviewed; description updated. Policy statement unchanged.
07/20/2015: Code Reference section updated for ICD-10.
10/27/2015: Policy description updated regarding tests. Policy statement unchanged. Investigative definition updated in policy guidelines section.
SOURCE(S)Blue Cross Blue Shield Association policy # 2.04.69
CODE REFERENCEThis may not be a comprehensive list of procedure codes applicable to this policy.