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Crohn Disease: Differential Diagnoses & Workup

Author: George Y Wu, MD, PhD, Professor, Department of Medicine, Director, Hepatology Section, Herman Lopata Chair in Hepatitis Research, University of Connecticut School of Medicine
Coauthor(s): Marcy L Coash, DO, Staff Physician, Department of Internal Medicine, University of Connecticut; Senthil Nachimuthu, MD, FACP, Fellow, Department of Internal Medicine, Heart and Vascular Institute, Tulane University School of Medicine
Contributor Information and Disclosures

Updated: Jan 20, 2009

Differential Diagnoses

Amebiasis
Carcinoid Tumor, Intestinal
Diverticulitis

Other Problems to Be Considered

Acute appendicitis
Endometriosis (Yersinia enterocolitica)¹
Ileocecal tuberculosis
Systemic vasculitis
Tubo-ovarian pathologies

Workup

Laboratory Studies

• Laboratory study findings in the evaluation of Crohn disease may indicate the presence of inflammatory activity or nutritional deficiencies.
  • Anemia may be due to multiple causes, including chronic inflammation, iron malabsorption, chronic blood loss, and malabsorption of vitamin B-12 or folate.
  • Leukocytosis may be due to chronic inflammation, abscess, or steroid treatment.
  • Hypoalbuminemia, hypocholesterolemia, hypocalcemia, hypomagnesemia, and hypoprothrombinemia may reflect malabsorption.
  • Acute inflammatory markers, such as C-reactive protein (CRP) and orosomucoid, correlate closely with disease activity. The erythrocyte sedimentation rate (ESR) is thought to be more helpful in assessing the disease activity of Crohn colitis than ileitis.
  • Stool samples should be tested for routine pathogens, ova, parasites, and Clostridium difficile toxin. These studies should also be checked to rule out infectious etiologies during relapses and before initiating immunosuppressive agents.⁶
• Two serologic tests are available to attempt to differentiate ulcerative colitis from Crohn disease.
  • Perinuclear antineutrophil cytoplasmic antibody (p-ANCA), a myeloperoxidase antigen, is more commonly found in ulcerative colitis, whereas antibodies to the yeast Saccharomyces cerevisiae (ie, anti-S cerevisiae antibodies [ASCA]) are more commonly found in Crohn disease.
  • Therefore, a test result positive for p-ANCA antigen and negative for ASCA suggests the diagnosis of ulcerative colitis; conversely, a test result positive for ASCA and negative for p-ANCA antigen suggests the presence of Crohn disease.
  • However, these tests are only recommended as an adjunct to clinical diagnosis, as the test results are not specific and have been found to be positive in other bowel diseases.
  • Additional serologic markers such as Escherichia coli anti-ompC (outer membrane porin C) can be found in >50% of Crohn disease cases, and only a small percentage of ulcerative colitis case. Pseudomonas fluorescens (anti-12) may be found in >50% of Crohn disease cases and only 10% of ulcerative colitis cases. Flagellin-like antigen (anti-Cbir1) is associated independently with small bowel, intestinal penetrating, and fibrostenosing disease. These tests further increase sensitivity and diagnostic value.
  • These tests can provide prognostic information as well. Patients with Crohn disease whose condition is ASCA positive have a higher rate of surgery and require surgery earlier in the course of the disease, independent of the disease location.^1,2,6

Imaging Studies

• Barium contrast studies
  • These studies are very useful in defining the nature, distribution, and severity of Crohn disease. An experienced radiologist should perform these studies to obtain the most information.
  • An upper GI series, together with a small bowel follow-through (SBFT) and spot films of the terminal ileum, is the initial diagnostic procedure of choice in most patients who present with typical symptoms of Crohn disease.
  • SBFT can only indirectly detect alteration of the small bowel wall, and its sensitivity to detect marginal changes is low in comparison with direct inspection of the mucosa by endoscopy.
  • Once the patient can tolerate the procedure, barium enema may help in the evaluation of colonic lesions. Barium contrast studies are useful in evaluating features such as rigidity, pseudodiverticula, fistulization, and submucosal edema. These studies are noninvasive and usually well tolerated. In patients with ileitis, the terminal ileum may not be visualized, possibly because of spasming of the ileocecal valve.
  • Radiographic findings in both the small and large bowel parallel the clinical pattern.
  • Edema and ulceration of the mucosa in the small bowel may appear as thickening and distortion of valvulae conniventes. Edema of the deep layers of the bowel wall results in separation of the barium-filled bowel loops.
  • Tracking of deep ulcerations, both transversely and longitudinally, results in a cobblestone appearance.
  • Ileitis can also manifest as a string sign on barium study secondary to spasms or, rarely, because of fibrotic stricturing.
  • Fistulae can also be detected by barium studies of the digestive tract or through injection into the opening of the suspected fistulae.^10,11,12
• Computed tomography (CT) scanning is helpful in the assessment of extramural complications such as fistulae and abscesses, as well as hepatobiliary and renal complications. CT enterography can be helpful in the assessment of subtle mucosal damage.^10,11,12
• Magnetic resonance imaging (MRI) can be superior to CT scanning in demonstrating pelvic lesions. Because of differential water content, MRI can differentiate active inflammation from fibrosis, and it can distinguish between inflammatory and (fixed) fibrostenotic lesions in Crohn disease.^10,11,12
• Ultrasonography is helpful in differentiating tubo-ovarian pathology. However, this modality can also detect enlarged lymph nodes, abscesses, stenoses, and even fistulae, and ultrasonography is regarded as a quick and inexpensive screening method to aid in the diagnosis of IBD or to repeatedly evaluate patients for complications.^10,11,12
• Rectal endoscopic ultrasonography has been used as an alternative to MRI in the assessment of perianal disease. This technique allows the differentiation of simple from complex fistulae, as well as the assessment of the tracts of the fistulae in relation to the sphincter muscle.^10,11,12
• Radionucleotide scanning may be helpful in assessing the severity and extent of the disease in patients who are too ill to undergo colonoscopy or barium studies.^10,11,12

Procedures

• Colonoscopy
  • Colonoscopy can be helpful when single-contrast barium enema has not been informative in evaluating a colonic lesion.
  • Colonoscopy is useful in obtaining biopsy tissue, which helps in the differentiation of other diseases, in the evaluation of mass lesions, and in the performance of cancer surveillance.
  • Colonoscopy also enables dilation of fibrotic strictures in patients with long-standing disease. Colonoscopy may also be used in the postoperative period to evaluate surgical anastomoses to predict the likelihood of clinical relapse as well as the response to postoperative therapy.¹
• Upper endoscopy
  • Upper endoscopy with biopsy is helpful in differentiating Crohn disease from peptic ulcer disease in patients with upper GI tract symptoms.
  • Endoscopic retrograde cholangiopancreatography (ERCP) is helpful both as a diagnostic procedure and a therapeutic tool in patients with sclerosing cholangitis and stricture formation.
  • Endoscopic ultrasonography (EUS) and magnetic resonance cholangiopancreatography (MRCP) may provide equally valuable information without invasive complications.
  • Double balloon endoscopy allows complete evaluation of the small bowel and makes distal ileal biopsies feasible.
  • Wireless capsule endoscopy helps to identify involvement of the upper GI tract which will occur in 40% of patients with Crohn disease. However, drawbacks include the inability to take biopsies, the risk of acute obstruction in stricturizing disease, and the time required for analysis.
  • Endoscopy can also be helpful in the detection of complications of Crohn disease. Magnifying endoscopy allows a more detailed view of the mucosal surface than conventional endoscopy. In combination with chromoendoscopy (indigo carmine), it is possible to further analyze the surface staining pattern to help identify neoplastic changes in situ.^6,10,11,12

Histologic Findings

Transmural involvement with noncaseating granulomas is seen in about 50% of cases of Crohn disease. Patchy skip lesions and lymphoid aggregates may also be seen throughout the bowel.⁴

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