Faecal calprotectin

Faecal calprotectin is excreted in excess into the intestinal lumen during the inflammatory process and so can act as a marker for inflammatory diseases of the lower gastrointestinal tract. Tests measuring faecal calprotectin can help to distinguish between inflammatory bowel diseases and non-inflammatory bowel diseases (1).

• Calprotectin is a 36-kDa calcium and zinc binding protein that accounts for about 60% of total proteins in the cytosol fraction in neutrophil granulocytes
  • calprotectin has an antimicrobial activity
  • calprotectin is probably involved in the regulation of inflammatory reactions
  • calprotectin is resistant both in vitro and in vivo to enzymatic degradation - levels of calprotectin can be easily measured in the stools

NICE have stated (1):

• faecal calprotectin testing is recommended as an option to support clinicians with the differential diagnosis of inflammatory bowel disease (IBD) or irritable bowel syndrome (IBS) in adults with recent onset lower gastrointestinal symptoms for whom specialist assessment is being considered, if:
  • cancer is not suspected, having considered the risk factors (for example, age)
• faecal calprotectin testing is recommended as an option to support clinicians with the differential diagnosis of IBD or non-IBD (including IBS) in children with suspected IBD who have been referred for specialist assessment, if:
  • appropriate quality assurance processes and locally agreed care pathways are in place for the testing

Evidence:

• an increase in faecal calprotectin levels in IBD and colorectal cancer has been reported (2,3,4)
  • faecal calprotectin levels in Crohn's disease and ulcerative colitis (UC) appear to closely correlate with the faecal excretion of 111-indium-labelled leucocytes (which is considered to be the gold standard for measuring intestinal inflammation)
  • study evidence has shown that (2):
    • faecal calprotectin was significantly increased in Crohn's disease, ulcerative colitis and neoplasms, whereas normal values were found in patients with irritable bowel syndrome and in healthy subjects
    • a positive correlation was observed with clinical activity scores in Crohn's disease and ulcerative colitis
      • clinically active disease showed higher calprotectin levels than those observed in patients with quiescent disease
  • faecal calprotectin proved to be an even stronger predictor of clinical relapse in UC than in CD, which makes the test a promising non-invasive tool for monitoring and optimising therapy (3)
• a further study revealed that, in unselected outpatients referred for colonoscopy, a single measurement of faecal calprotectin is not sufficiently accurate to identify those with significant disease. However, a normal result can help in ruling out organic disease among patients with diarrhoea and those with abdominal pain and/or constipation (4)
• a study showed (5):
  • elevated pre-diagnostic faecal calprotectin levels were common in patients with colorectal cancer (CRC) in close proximity to diagnosis
  • right-sided localization and tumor stage were significantly associated with a rise in faecal calprotectin levels
• in children (6):
  • calprotectin is a sensitive, but not disease specific, marker to easily detect inflammation throughout the whole gastrointestinal tract. It may help in identifying an organic disease characterized by intestinal mucosa inflammation and in the differential diagnosis of functional bowel disorders

A review notes (7):

• Faecal calprotectin testing
  • is recommended in patients <60 years old with lower gastrointestinal symptoms and normal initial workup to exclude causes of colonic inflammation
  • a normal faecal calprotectin result has a high negative predictive value for inflammatory bowel disease, and prevents unnecessary investigation when the most likely diagnosis is irritable bowel syndrome
  • should not be used in patients older than 60 or if colorectal cancer is suspected
  • is a sensitive marker of intestinal inflammation and may be elevated in conditions other than inflammatory bowel disease, such as diverticulitis and infectious gastroenteritis, or when patients take medications such as non-steroidal anti-inflammatory drugs (NSAIDs) and aspirin

Reference:

1. NICE (October 2013). Faecal calprotectin diagnostic tests for inflammatory diseases of the bowel
2. Costa F et al. Role of faecal calprotectin as non-invasive marker of intestinal inflammation. Dig Liver Dis. 2003 Sep;35(9):642-7.
3. Costa F et al. Calprotectin is a stronger predictive marker of relapse in ulcerative colitis than in Crohn's disease. Gut. 2005 Mar;54(3):364-
4. Meucci G et al. Diagnostic value of faecal calprotectin in unselected outpatients referred for colonoscopy: A muticenter prospective study. Digestive and Liver Disease 2006;38(Supp.1): S32.
5. Blad N, Palmqvist R, Karling P. Pre-diagnostic faecal calprotectin levels in patients with colorectal cancer: a retrospective study. BMC Cancer. 2022 Mar 24;22(1):315.
6. Cananin RB et al. Diagnostic value of faecal calprotectin in paediatric gastroenterology clinical practice.Digestive and Liver Disease 2004; 36 (7): 467-470.
7. Deputy M, Devanaboina R, Al Bakir I, Burns E, Faiz O. The role of faecal calprotectin in the diagnosis of inflammatory bowel disease BMJ 2023; 380 :e068947 doi:10.1136/bmj-2021-068947