Diagnosis of Crohn’s Disease
The diagnosis of Crohn’s disease (CD) and its differentiation from ulcerative colitis (UC) and other intestinal disorders is based on the combination of a number of factors, including the patient history and physical examination, laboratory test results, radiologic studies, and endoscopy with biopsy and histologic examination. None of these diagnostic tools is 100% accurate; however, a combination of observations and tests raises the index of suspicion for the presence of inflammatory bowel disease. Discussed within this module are a number of diagnostic clues that are helpful for confirming the diagnosis of CD or UC.
Patient History and Physical Examination
The hallmark manifestations of Crohn’s disease (CD) are fatigue, prolonged diarrhea and abdominal pain with or without gross bleeding, weight loss, and fever. Due to the transmural nature of the inflammation and the variability in extent of gastrointestinal involvement, the clinical manifestations can be quite variable.
For many patients with inflammatory bowel disease
(IBD), symptoms may be present for an extended period of time before
a confirmed diagnosis is made. Contributing to this delay is the fact
that many of the symptoms associated with IBD are also associated
with irritable bowel syndrome (IBS). Pimentel, et al., studied the
duration and nature of patient complaints before the diagnosis of
CD and ulcerative colitis (UC) and determined the role of IBS during
this time (the prodromal period). In an analysis of 66 patients, (45
with CD; 21 with UC), the length of time symptoms were present before
diagnosis was 7.7 ± 10.7 years for CD and 1.2 ± 1.8 years
for UC
The initial presentation of CD for some patients may be a disease complication such as a fistula, abscess, or stricture. In some cases, an extraintestinal manifestation is the presenting symptom. Some common symptoms of CD include:
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Abdominal pain and tenderness
Crampy abdominal pain is a common symptom of CD. Strictures may lead to small-bowel or colonic obstruction. Patients with disease limited to the distal ileum may present late and only with evidence of constipation due to obstruction. Inflammation in the ileocecal area may result in right lower quadrant tenderness and a palpable mass on physical examination.
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Bleeding
Gross bleeding is unusual in CD unless the distal (descending) colon is involved. Many patients (regardless of disease location) will have stools that test positive for the presence of occult blood.
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Weight loss
Many people with IBD experience discomfort when they eat and decrease their food intake as a result. In addition, CD can affect the surfaces of the intestine that are responsible for nutrient absorption, leading to malabsorption. The combination of these factors added to increased metabolic demands of the disease itself contribute to the common complaint of weight loss (or failure to gain weight appropriately in children), which is common in CD.
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Diarrhea
Diarrhea is a common feature of CD. Patients often provide a history of frequent, loose stools and nocturnal stooling.
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Fever
Fever is common in CD and may be a response to the inflammation or can occur secondary to perforation with complicating infection.
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Perianal disease
The clinical manifestations of other sites of intestinal involvement in CD are variable. Perianal disease occurs in up to one-third of patients with CD and may dominate the clinical picture. Signs and symptoms include:
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Perianal pain and drainage from large skin tags
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Anal fissures
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Perirectal abscesses
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Anorectal fistula
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Other signs and symptoms
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Patients with severe oral involvement may present with aphthous ulcers or other CD-related lesions and pain in the mouth and gums.
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The few patients with esophageal CD may present with odynophagia and dysphagia.
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For the 5% of patients with gastroduodenal CD, a peptic ulcer-like picture can occur with upper abdominal pain and symptoms of gastric outlet obstruction.
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The small percentage of patients whose disease predominantly involves the proximal small bowel may present with symptoms of fat malabsorption that may be confused with celiac disease.2012
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Endoscopy in Crohn’s Disease
Upper or lower gastrointestinal (GI) endoscopy is used to confirm the diagnosis of Crohn’s disease (CD), assess disease location, or obtain tissue for pathologic evaluation. Tissue biopsies can establish the diagnosis, differentiate between ulcerative colitis and CD, rule out some forms of acute self-limited colitis, or identify dysplasia or cancer. Lower GI endoscopic evaluation of surgical anastomoses can be used to predict the likelihood of clinical relapse and assess response to postoperative therapy.2012
Endoscopic Features of Crohn’s Disease
Endoscopic features of Crohn’s disease include:
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Areas of obvious inflammation interspersed with normal-appearing mucosa — these are referred to as skip lesions
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Focal ulcerations
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Polypoid mucosal changes that give an irregular look to the mucosal surface, known as a "cobblestone" appearance. Please see Fig.508
Intestinal biopsy helps confirm the diagnosis.6379
Figure 507 – Crohn’s Disease - Endoscopic Characteristics
Centocor. Data on file. 2006.
Some figures may not display clearly when rendered as a PDF or printed.
Figure 508 – Crohn’s Disease Endoscopic Findings
Centocor. Data on file. 2006.
Some figures may not display clearly when rendered as a PDF or printed.
Endoscopic visualization of the upper GI tract (esophagus, stomach, and duodenum) and the lower GI tract (colon and terminal ileum) is easily achieved with currently available technology. The ability to see most of the small intestine through endoscopic visualization is still limited. Development and refinement of capsule endoscopy is ongoing and has added to the ability of clinicians to visualize mucosa that is out of reach of traditional endoscopic equipment. Radiologic studies are valuable diagnostic tools when endoscopic visualization is either impossible or impractical.
Stool Tests Used in the Diagnosis of Crohn’s Disease
Two separate markers of inflammation that are detectable in stool specimens are calprotectin and lactoferrin. Both tests reflect the presence of neutrophils in the intestine. The reliability of direct measures of neutrophils in feces is limited by degeneration of cells that necessitates special handling and timely performance of the test, inability of testing methods to differentiate between neutrophils and other types of leukocytes, and other factors.2024
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Fecal lactoferrin
Lactoferrin is a multifunctional protein that is found in milk, in mucosal secretions, and in neutrophils. As a marker of the presence of activated neutrophils, increased levels of lactoferrin in feces correlate with intestinal inflammation. Lactoferrin is not found in other types of leukocytes; its presence is both sensitive and specific for neutrophils. Tests for fecal lactoferrin have been shown useful in identifying the presence of inflammation and differentiating between inflammatory and noninflammatory causes of diarrhea.2024, 2025 Fecal lactoferrin does not differentiate between IBD and other inflammatory conditions such as bacterial infection. The utility of this laboratory test is to narrow the focus of investigation in cases of suspected IBD and may be useful to monitor disease activity and response to therapy.
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Fecal calprotectin
Calprotectin is a calcium-binding protein secreted by neutrophils and measurable in both plasma and stool. High levels of fecal calprotectin have been shown to reflect intestinal inflammation, leading to use of this surrogate marker to measure inflammation associated with IBD. Elevated levels of fecal calprotectin correlate with intestinal inflammation and are predictive for relapse.2026 Bunn, et al., investigated the correlation between fecal calprotectin levels and invasive measures of inflammation in children with IBD. When compared with inflammation confirmed by endoscopic and histologic evaluation or technetium-99 white-cell scanning, fecal calprotectin correlated closely with these more invasive tests.2709 Used in the initial diagnostic evaluation of children with suspected inflammation, Fagerberg and colleagues determined that fecal calprotectin demonstrated a 95% sensitivity, 93% specificity, 95% positive predictive value, and 93% negative predictive value for the detection of colonic inflammation.2028 In a cohort of 49 children with suspected IBD, Canani, et al., demonstrated increased sensitivity and specificity by using fecal calprotectin in combination with other noninvasive tests (ASCA/p-ANCA, small intestine permeability, and bowel-wall ultrasonography). Investigators concluded that positive results of the combined measures tested demonstrated a greater than 99% probability of having IBD.2029
In addition to its utility in the initial diagnostic evaluation of intestinal inflammation, calprotectin has utility as a predictor of relapse, with increased levels demonstrating a 14-fold risk of relapse in patients with UC; significantly stronger as a predictor than when used to predict relapse in CD.2030 As with fecal lactoferrin, fecal calprotectin may be elevated in the presence of non-IBD intestinal inflammation, such as infection. It may also be elevated due to enteropathy that results from use of nonsteroidal anti-inflammatory drugs.2031 Fecal calprotectin levels have been evaluated in first-degree relatives and in cohabitants of patients with UC and compared to patient levels. Investigators found that fecal calprotectin levels were highest in patients with UC and significantly higher than controls in first-degree relatives. Fecal calprotectin levels in spouses were higher than in healthy controls, but lower than in first-degree relatives, a finding that continues to raise the question of the role of genetic predisposition in combination with environmental factors in the etiology of UC.2032
Content on this page was last reviewed on October 31, 2009.
Content on this page was last changed on March 25, 2009.
References:| 2012. | Hanauer SB, Sandborn W; Practice Parameters Committee of the American College of Gastroenterology. Management of Crohn’s disease in adults. Am J Gastroenterol. 2001;96(3):635-643. |
| 2024. | Fine KD, Ogunji F, George J, Niehaus MD, Guerrant RL. Utility of a rapid fecal latex agglutination test detecting the neutrophil protein, lactoferrin, for diagnosing inflammatory causes of chronic diarrhea. Am J Gastroenterol. 1998;93(8):1300-1305. |
| 2025. | Kane SV, Sandborn WJ, Rufo PA, et al. Fecal lactoferrin is a sensitive and specific marker in identifying intestinal inflammation. Am J Gastroenterol. 2003;98(6):1309-1314. |
| 2026. | Tibble JA, Sigthorsson G, Bridger S, Fagerhol MK, Bjarnason I. Surrogate markers of intestinal inflammation are predictive of relapse in patients with inflammatory bowel disease. Gastroenterology. 2000;119(1):15-22. |
| 2028. | Fagerberg UL, Lööf L, Myrdal U, Hansson LO, Finkel Y. Colorectal inflammation is well predicted by fecal calprotectin in children with gastrointestinal symptoms. J Pediatr Gastroenterol Nutr . 2005;40(4):450-455. |
| 2029. | Canani RB, de Horatio LT, Terrin G, et al. Combined use of noninvasive tests is useful in the initial diagnostic approach to a child with suspected inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2006;42(1):9-15. |
| 2030. | Costa F, Mumolo MG, Ceccarelli L, et al. Calprotectin is a stronger predictive marker of relapse in ulcerative colitis than in Crohn’s disease. Gut. 2005;54(3):364-368. |
| 2031. | Tibble JA, Sigthorsson G, Foster R, et al. High prevalence of NSAID enteropathy as shown by a simple faecal test. Gut. 1999;45(3):362-366. |
| 2032. | Montalto M, Curigliano V, Santoro L, et al. Fecal calprotectin in first-degree relatives of patients with ulcerative colitis. Am J Gastroenterol. 2007;102(1):132-136. |
| 2083. | Drossman D. Appendix A: Diagnostic Criteria for Functional Gastrointestinal Disorders. In: Drossman, DA. ROME II: Diagnostic Criteria for the Functional Gastrointestinal Disorders. 2nd ed., MacLean, VA: Degnon Associates; 2000:659-668. |
| 2140. | Pimentel M, Chang M, Chow EJ, et al. Identification of a prodromal period in Crohn’s disease but not ulcerative colitis. Am J Gastroenterol. 2000;95(12):3458-3462. |
| 2709. | Bunn SK, Bisset WM, Main MJ, et al. Fecal calprotectin: validation as a noninvasive measure of bowel inflammation in childhood inflammatory bowel disease. J Pediatr Gastroenterol Nutr . 2001;33(1):14-22. |
| 6379. | Stange EF, Travis SPL, Vermeire S, et al. European evidence based consensus on the diagnosis and management of Crohn’s disease: definitions and diagnosis. Gut. 2006;55(suppl 1):il-i15. |
| 8253. | Centocor. Data on file. 2006. |
| 8254. | Centocor. Data on file. 2006. |
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