Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are two chronic conditions associated with diarrhea and abdominal pain, and these symptoms are among the most common reasons that patients seek medical advice. Differential diagnosis between IBD and IBS is very important because IBD and IBS have very different underlying pathophysiologies and IBD can become life threatening, requiring extensive life long treatment and/or surgery. In contrast, IBS can often be treated with dietary restrictions, stress reduction and nutriceutical/nutritional supplements or medication, and is not associated with rectal bleeding.
IBD encompasses Ulcerative Colitis (UC) and Crohn’s Disease (CD), which are incurable, idiopathic inflammatory diseases of the gastrointestinal (GI) tract. UC is isolated almost exclusively in the colon, but CD occurs in various segments of the GI tract; the anatomical location and degree of inflammation determine the predominant symptoms, which may include rectal bleeding. 1 IBS does not involve inflammation or rectal bleeding, and is considered a functional disorder caused by abnormal GI motility, altered pain perception, food sensitivity, or dysbiosis. 1 In the absence of rectal bleeding, clinical differentiation between IBD and IBS has been difficult without invasive endoscopy. DDI uses a highly sensitive and specific immunoassay that has recently been developed to measure the fecal concentration of the inflammatory protein, lactoferrin, which facilitates noninvasive differentiation between IBD and IBS.
Fecal lactoferrin, an iron binding glycoprotein derived from polymorphonuclear neutrophils, is elevated with IBD 1,2 but not IBS. 1,3 During intestinal inflammation, leukocytes infiltrate the mucosa, which results in increased lactoferrin in the feces. 1,4,5 Leukocyte-derived lactoferrin is resistant to proteolysis and freeze thaw cycles. 1
Clinical studies have shown that fecal lactoferrin levels of healthy persons (1.6mg/ml) are similar to IBS patients (1.3m g/ml), but markedly increased in patients with active IBD [1,3]. Patients with IBD oscillate between active and inactive disease states, and fecal lactoferrin increases 2-3 weeks prior to onset of clinical symptoms. 6 During remission and effective treatment, fecal lactoferrin decreases significantly. Therefore, disease activity and efficacy of treatment can be monitored by following fecal lactoferrin levels. The test can be ordered separately, after the initial Comprehensive Stool Analysis, to track disease activity in patients with IBD.
Moderately elevated levels of fecal lactoferrin may be found with red cells and leukocytes, in association with inflammatory diarrhea caused by enteroinvasive pathogens. 7,8 Such levels are typically lower than those associated with even the inactive phase of IBD, and likely the result of acute damage/inflammation of the intestinal mucosa. With moderately elevated levels of fecal lactoferrin, one should check for the presence of enteroinvasive pathogens (eg. Shigella, Campylobacter, C. difficile).
1 Kane S, Sandborn W, Rufo P et al. Fecal lactoferrin is a sensitive and specific marker in identifying intestinal inflammation. Am. J. Gastroenterol. 2003; 98:1309-14
2 Sugi K, Saitoh O, Hirato I et al. Fecal lactoferrin as a marker for disease activity in inflammatory bowel disease: A comparison with other neutrophil-derived proteins. Am. J. Gastroenterol. 1996; 91:927-33
3 Buderus S, Lohmann N, Lentze M et al. Clinical evaluation of the IBD-CHEK Test for detecting elevated fecal lactoferrin as an indicator of intestinal inflammation in pediatric patients. Suppl. Gastroenterol. 2002; 122:A-219:S1392
4 Baveye S, Elass, E, Mazurier J et al. Lactoferrine: A multifunctional glycoprotein involved in the modulation of the inflammatory response. Clin. Lab. Med. 1999;37: 281-286
5 Fine K, Ogunji F, George J et al. Utility of a rapid fecal latex agglutinization test detecting the neutrophil protein, lactoferrin, for diagnosing inflammatory causes of chronic diarrhea. Am. J. Gastroenterol. 1993; 93:1300-1305
6 Walker T, Sandborn W, Boone J et al. Fecal lactoferrin measurements are useful in the interval assessment of patients with active and inactive inflammatory bowel disease. Am. J. Gastroenterol. 2003; 98: S246:742
7 Huicho L, Garaycochea V, Uchima N et al. Fecal lactoferrin, fecal leukocytes and occult blood in the diagnostic approach to childhood invasive diarrhea. Ped. Infect. Dis. J. 1997; 16:644-647
8 Guerrant R, Araujo V, Soares E et al. Measurement of fecal lactoferrin as a marker of fecal leukocytes. J. Clin. Microbiol. 1992; 30:1238-1242