Crohn disease, also known as regional enteritis, is an idiopathic inflammatory bowel disease characterized by widespread discontinuous gastrointestinal tract inflammation. The terminal ileum and proximal colon are most often affected. Extraintestinal disease is common.
The diagnosis is typically made between the ages of 15 and 25 years with no gender predilection 5. There is a familial component and incidence varies geographically.
Patients typically present with chronic diarrhea and recurrent abdominal pain, although occasionally the presentation is with a complication or an extraintestinal manifestation. Anemia may be present and C-reactive protein may be elevated 29.
Fecal calprotectin has been increasingly used in recent years to:
- distinguish inflammatory bowel disease from irritable bowel syndrome
- assess disease activity in inflammatory bowel disease, including acute exacerbations and response to treatment 26
Crohn disease remains idiopathic, although infective agents have been gaining in popularity as a possible cause, including the measles virus and atypical mycobacterium. As there are definite genetic factors at play, multiple factors are likely to contribute 1. Incidence is higher in people with first degree relatives having IBD, reaching up to 10%. Also, there has been shown 30-50% chance of developing the disease in mono- or heterozygous twins.
Initially, the disease is limited to the mucosa with neutrophilic cryptitis and lymphoid hyperplasia, lymphoedema and shallow aphthoid ulceration. As the disease progresses, the entire bowel wall becomes involved, with linear longitudinal and circumferential ulcers extending deep into the bowel wall, predisposing to fistulae. Inflammation also extends into the mesentery and over time leads to chronic fibrotic change, and stricture formation 5.
Inflammation can occur anywhere along the digestive tract, including the mouth and esophagus.
- mucogingivitis, mucosal tags, deep ulceration, cobblestoning, lip swelling and pyostomatitis vegetans, esophageal ulcers and strictures
Extraintestinal manifestations include 3,15-17:
- uveitis (acute anterior uveitis)
- liver and biliary system
- renal calculi containing oxalate. The poor fat absorption results in binding of calcium by fats, which in turn reduces the amount of calcium that can bind to oxalate, therefore increasing the amount of unbound oxalate available for resorption; this resorption occurs in the colon, and therefore patients with an ileostomy do not have the same increased risk.
- ileoureteral / ileovesical fistula 31,32
- pulmonary and thoracic associations
The characteristic of Crohn disease is the presence of skip lesions and presence of discrete ulcers. The frequency with which various parts of the gastrointestinal tract are affected varies widely 5:
- small bowel: 70-80% 5,6; the terminal ileum is usually affected first 33
- small and large bowel: 50%
- large bowel only: 15-20%
The choice of investigation modality depends on local expertise and availability. CT and MR enteroclysis are similar in sensitivity for active inflammation (89% vs 83% respectively) and both are somewhat better than small bowel follow-through (67-72%) 6. The lack of ionising radiation from MRI would make it a better option, however, the availability of MRI is limited in many countries.
Ultrasound is also an option for diagnosing active disease, follow-up and assessing complications 20. Reported sensitivity 75-94% and specificity 67-100% 20.
Features on barium small bowel follow-through include:
- mucosal ulcers
- widely separated loops of bowel due to fibrofatty proliferation (creeping fat) 2
- thickened folds due to edema
- pseudodiverticula formation: due to contraction at the site of ulcer with ballooning of the opposite site
- string sign: tubular narrowing due to spasm or stricture depending on the chronicity
- partial obstruction
- on control films presence of gallstones, renal oxalate stones, and sacroiliac joint or lumbosacral spine changes should be sought
Ultrasound has a limited role, but due to it being cheap and available and not involving ionising radiation, it has been evaluated as an initial screening tool for active disease and also for follow-up and to assess complications 4,20. Typically examination is limited to the small bowel and wall thickness assessed:
- bowel wall thickness should be <3 mm
The usefulness of this finding needs to be interpreted in the context of pretest probability (i.e. thickness of less than 3 mm helps exclude the disease in a low-risk patient, and a thickness of greater than 4 mm helps establish the diagnosis in a high-risk patient) 4. As it has difficulty examining the whole bowel, it is not appropriate as a true diagnostic test.
On Doppler evaluation, increased superior mesenteric artery (SMA) flow volume and decreased SMA resistive index (SMA RI) also correlate with disease activity. Successful treatment may result in the normalization of these imaging parameters 12.
Other features on ultrasound 20:
- non-compressible, rigid, fixed bowel wall
- perienteric fluid
- creeping fat - echogenic area (representing proliferation of adipose tissue that extends around active inflammation) separating bowel loops
- gut signature - lost or preserved
- strictures - fibrotic (maintains gut signature) or inflammatory (loss of gut signature)
Ultrasound does, of course, have a significant role to play in the assessment of:
- perianal disease: rectal ultrasound, endoanal ultrasound
- hepatobiliary disease
CT examination can be carried out with both intravenous and intraluminal contrast (positive or negative) 5:
- fat halo sign: submucosal fat deposition
- comb sign: engorgement of the vasa recta
- mucosal and mural hyperenhancement
- bowel wall thickening (1-2 cm) which is most frequently seen in the terminal ileum (present in up to 83% of patients) 8
- strictures and fistulae, with upstream dilatation
- perienteric fat stranding
- mesenteric/intra-abdominal abscess or phlegmon formation 8
- abscesses are eventually seen in 15-20% of patients 8
CT is also able to give valuable information on:
- perianal disease
- hepatobiliary disease
MRI enterography has no ionising radiation and an ability to evaluate both mural and extramural involvement. It has become an increasingly important part of the management of patients with Crohn disease. MRI enteroclysis may be attempted in select patients.
MR enterography can be a useful technique for evaluation of the bowel. Inflamed loops of bowel demonstrate thickening >3 mm and increased mural contrast enhancement 22. Increased T2W signal in the thickened bowel wall is particularly helpful in evaluating for acute inflammation 25.
Extramural disease is where MRI excels:
- fibrofatty proliferation
- thickening of extramural fat, which separates bowel loops
- equivalent to the fat halo sign on CT
- vascular engorgement: comb sign
- stenoses and strictures
Coronal cine sequences (bSSFP) can also be useful in diagnosis. Inflamed loops of bowel frequently demonstrate decreased peristalsis.
MRI enteroclysis requires the placement of a nasojejunal catheter through which 1.5-2 L of contrast solution (e.g. water with polyethylene glycol and electrolytes) are injected 2.
Spatial resolution is not as good as with conventional fluoroscopic enteroclysis, and thus minor mucosal changes are not apparent. When the disease is transmural, with cobblestone appearance, the abnormalities are evident as high T2 signal linear regions, provided adequate distension is achieved 2.
Standard MRI can also give valuable information:
- perianal disease
- hepatobiliary disease
- sacroiliac joints, spine and large joints
Treatment and prognosis
Management is complex as the condition is chronic with a relapsing-remitting course. Medical management includes corticosteroids, 5-ASA preparations, immunomodulation (e.g. azathioprine, cyclosporine, methotrexate) 7. Surgical management is reserved for complications including:
- adhesions and bowel obstructions
- perianal disease
History and etymology
It is named after Burrill Bernard Crohn (1884-1983), an American gastroenterologist, who described the condition as 'regional ileitis' in his seminal 1932 paper 11,24. However, the first definite description (but see below) was nearly twenty years prior, by Sir T (Thomas) Kennedy Dalziel (1861-1924), a Scottish surgeon, in 1913 21,23.
Antoni Leśniowski (1867-1940), a Polish surgeon, described a small bowel condition in 1904 in a small series of four patients, with similarities to Crohn disease, although it remains controversial if it was actually Crohn's 27,28. At least one of the patients probably actually had ileal tuberculosis. Nevertheless Polish physicians and journals usually call the condition Lesniowski-Crohn disease.
The differential diagnosis depends on the presenting symptom. When terminal ileitis is the main presentation, then differentials (adjusted for patient's age) include 1:
When colonic involvement is the predominant feature then other considerations include:
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