Approach

The diagnosis of Crohn disease (CD) is suggested by a typical history supported by physical findings, especially perianal involvement and radiologic and endoscopic investigations.

The clinical presentation of CD and the order of investigations performed varies based on the part of the gastrointestinal tract involved, the degree of inflammation, and presence of complications. The American Gastroenterological Association (AGA) suggests using a combination of biomarker-based plus symptom-based monitoring strategy over symptom-based strategy alone in patients with CD in symptomatic remission.[66]

History

A family history of inflammatory bowel disease (IBD) increases the likelihood of CD. Approximately 12% of patients have a family history of CD.[57]​ It is more common in white than black or Asian people, and in individuals of Ashkenazi Jewish origin.[11][19][20]​ Ashkenazi Jews have a two- to fourfold increased risk of CD.​​​[56]

The onset of CD typically occurs in the second to fourth decade of life with a smaller peak from 50-60 years.[11][12][13]

The clinical picture of CD includes different combinations of symptoms including fatigue, diarrhea, abdominal pain, weight loss, fever, and gastrointestinal bleeding.​[9][12]​​​​ Diagnosis can be difficult in view of nonspecific symptoms.

Exclude alternative causes

The history should also exclude alternative causes for symptoms. Recent travel, recent antibiotic use, or contact with sick people suggest an infectious cause for diarrhea.

Intestinal tuberculosis (TB) is an important differential diagnosis that should not be missed.[67] Mistakenly treating patients for CD with immunosuppression could be life-threatening.[68] In cases of high suspicion, patients may require empiric treatment for TB under specialist guidance.[69] See Extrapulmonary tuberculosis.

Physical exam

Patients present with a constellation of abdominal findings including right lower quadrant abdominal tenderness, and palpable abdominal mass.

The following should be performed:

  • Oral inspection for ulcers

  • Abdominal exam for masses or pain

  • Perineal inspection for perianal skin tags, fistulae, abscesses, and sinus tracts

  • Digital rectal exam for occult blood and exclusion of a mass

The skin should be inspected for signs of extraintestinal skin manifestations of CD, such as erythema nodosum and pyoderma gangrenosum. Body mass index should be calculated as a baseline for future changes in weight.[Figure caption and citation for the preceding image starts]: A patient's arms and hands show the presence of erythema nodosumCDC/ Margaret Renz [Citation ends].com.bmj.content.model.Caption@f988911

Initial laboratory investigations

All patients should have a complete blood count, comprehensive metabolic panel, C-reactive protein, and erythrocyte sedimentation rate on initial presentation.[9][70][71]​​​ Serum iron studies and vitamin B12 and folate levels should be performed.[71][72]

Stool should be sent for microscopy (including for ova, cysts, and parasites) and culture.​[9][71]

Testing for Clostridium difficile toxin is indicated, especially if there is a history of recent antibiotic use.[9]​ C difficile infection is associated with increased short- and long-term mortality in patients with IBD.[73]

Yersinia enterocolitica serology should be requested in patients with clinical suspicion of ileitis.[74]

Imaging studies

Plain abdominal radiographs may be part of the initial tests ordered in the acute setting. They are not diagnostic of CD, but may be suggestive and help in assessing severity. Bowel loop distention and pneumoperitoneum may be visible.

Computed tomography (CT) and magnetic resonance (MR) studies

CT and MR studies offer higher-resolution imaging than contrast radiologic studies, as well as additional information on abdominal organs and structures (e.g., lymphadenopathy and malignancies) to aid diagnosis.[70][71]

Patients who are able to tolerate oral contrast are candidates for CT enterography or MR enterography.[75] CT enterography is sensitive (75% to 90%), and can assess for alternative diagnoses, and potential complications of CD (e.g., obstruction, abscess, fistula).[75] MR enterography characteristics (sensitivity 77% to 82%, specificity 80% to 100%) are similar to those of CT enterography, but availability may be limited.[75] MR imaging has also been shown to yield robust diagnostic accuracy in detecting fibrotic strictures, distinguishing between fibrotic and inflammatory strictures, and evaluating stricture severity in patients with CD.[76]​ Guidelines suggest that MR enterography should be the test of choice as it does not expose the patient to ionizing radiation.[70][71][77]

[Figure caption and citation for the preceding image starts]: CT scan demonstrating thickening of the terminal ileum in a patient with Crohn disease exacerbationProvided by Drs Wissam Bleibel, Bishal Mainali, Chandrashekhar Thukral, and Mark A. Peppercorn, the previous authors of this topic [Citation ends].com.bmj.content.model.Caption@4987c5fc[Figure caption and citation for the preceding image starts]: CT scan demonstrating thickening of the terminal ileum in a patient with Crohn disease exacerbationProvided by Drs Wissam Bleibel, Bishal Mainali, Chandrashekhar Thukral, and Mark A. Peppercorn, the previous authors of this topic [Citation ends].com.bmj.content.model.Caption@786b2efe

CT enterography and MR enterography are useful for postoperative assessment and evaluation of recurrence.[78]

If CT is indicated, do not order unenhanced CT alongside intravenous contrast-enhanced CT because the addition of unenhanced CT does not provide additional diagnostic information and exposes patients to unnecessary radiation.[75][79]​​​

Ultrasonography

Ultrasound of the abdomen and pelvis may be considered.[70][71][75]​​​ Sensitivity and specificity range from 75% to 94% and 67% to 100%, respectively.[75] Ultrasound may facilitate detection of extramural complications, detection and evaluation of stenotic strictures, and monitoring of disease course.[71][80]​​​ Obesity, overlying bowel gas, and guarding (in the acutely unwell patient) may preclude adequate compression of the ultrasound probe.[81]​ An accuracy comparable to CT or MR modalities has been noted for visualization of ileum when intestinal ultrasound is performed by trained practitioners.[81]​ Limitations of this technique include limited visualization of the stomach, esophagus, and rectum and inability for performing interventional procedure.[81]

Endoscopy

Ileocolonoscopy with biopsies should be performed in the assessment of suspected CD.[70][71][75]

Ileocolonoscopy and imaging studies are complementary in the diagnosis of CD.[70][71][75] Mucosal changes suggestive of CD include mucosal nodularity, erythema, edema, ulcerations, friability, stenosis, and the identification of fistulous tract opening.[71] Lesions are discontinuous, with intermittent areas of normal-appearing bowel (skip lesions). Evidence of a normal rectum and isolated involvement of the terminal ileum support the diagnosis.[Figure caption and citation for the preceding image starts]: Endoscopic view of Crohn ileitisProvided by Drs Wissam Bleibel, Bishal Mainali, Chandrashekhar Thukral, and Mark A. Peppercorn, the previous authors of this topic [Citation ends].com.bmj.content.model.Caption@7e41a99

Segmental colonic and ileal biopsies should be obtained to assess for microscopic evidence of CD.[70] The microscopic features that help distinguish ulcerative colitis and CD include granulomas, architectural change, and disease distribution.[82] Granulomatous inflammation is, however, reported in a minority of patients with CD (30% to 50%); it is not required for diagnosis.[71][82]

Biopsies of uninvolved mucosa help to identify the extent of histologic disease.[71] If TB is being considered, tissue from ileocecal biopsies can be tested and cultured for Mycobacterium tuberculosis.[69]

Esophagogastroduodenoscopy (upper gastrointestinal endoscopy) is not routinely required as part of the diagnostic evaluation, but may be performed in patients with upper gastrointestinal signs and symptoms.[70][71]

Capsule endoscopy can be used as an alternative to MR imaging to assess small bowel involvement. Patency capsule evaluation is advised prior to endoscopy to reduce the risk of capsule retention if there is a possibility of strictures.[71]

Fecal calprotectin

Fecal calprotectin is a noninvasive marker of bowel inflammation.[9][83]​​[84]​​​​​​​ It is released into feces when neutrophils gather at the site of any GI tract inflammation. In patients ages <60 years having lower GI symptoms and normal initial workup, fecal calprotectin testing can be performed to exclude causes of colonic inflammation. However, in patients ages >60 years with suspected colorectal cancer, fecal calprotectin testing should be interpreted with caution.

Fecal calprotectin can help to differentiate IBD from irritable bowel syndrome.[71] Fecal calprotectin is not specific for CD and can be increased in the stool in other gut pathologies (e.g., infectious gastroenteritis, diverticulitis, or colorectal cancer) or in patients on nonsteroidal anti-inflammatory drugs [NSAIDs] and aspirin).[71][85]​​ This lack of specificity limits its diagnostic role.

Fecal calprotectin is widely used in the primary care setting as a “rule out” test where IBD is unlikely in the presence of a normal calprotectin. In IBD it is used to monitor:[66][70][86][87][88]

  • relapse in patients with quiescent IBD, and

  • detection and monitoring of disease activity in symptomatic patients, potentially avoiding invasive and resource-intensive endoscopic monitoring.

Fecal calprotectin measurements may have a role in relapse prediction, assessment of treatment efficacy, and prediction of postsurgical relapse.[70][71]

The test has also been proposed for use in postoperative CD.[89]

A fecal calprotectin value of <150 micrograms/g and normal C-reactive protein (CRP) suggests no active inflammation in patients in symptomatic remission; endoscopic assessment can be avoided in such patients. However, elevated biomarker levels in these patients warrant an endoscopic evaluation.[66] ​In patients with CD with mild symptoms, biomarker levels alone cannot predict endoscopic activity, whereas in patients with moderate to severe symptoms, elevated fecal calprotectin or serum CRP suggests endoscopic activity and endoscopic evaluation can be avoided.[66]

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