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, lymphedema 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
- primary sclerosing cholangitis (PSC) (more common in ulcerative colitis)
- autoimmune hepatitis
- gallstones: seen in 30-50% 8
- hepatic abscess 8
- acute cholecystitis 3
- portal vein thrombosis (rare, yet higher than general population) 34
- fatty infiltration of the liver (steroid therapy, hyperalimentation) 31
- 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 ionizing 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/pseudosacculation formation: due to contraction at the site of ulcer with ballooning of the opposite (usually antimesenteric) 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 ionizing radiation, it has been evaluated as an initial screening tool for active disease and also for follow-up and to assess complications 4,20. Features which may be discovered during transabdominal sonography include 39:
- small bowel wall thickening (>3-4 mm)
- needs to be interpreted in the context of pretest probability
- affected loops often non-compressible and are difficult to displace with transducer pressure
- affected segments lose peristaltic activity 38
- loss of mural stratification
- the gut signature is characteristic of small bowel
- chronic disease activity may result in collagen deposition within the wall, which imitates the appearance of the normal submucosa
- bowel wall hyperemia
- hyperechoic, circumferential layer external to bowel wall
- represents fibrofatty proliferation, thought to represent active inflammation
- interruption by hypoechoic mesenteric streaks imply a greater degree of inflammation
- mesenteric lymphadenopathy
- three or more mesenteric lymph nodes enlarged, measured over 4 mm (width) or 8 mm (length)
free intraperitoneal fluid
- thought to be secondary to transmural inflammation
Using a subset of the aforementioned, the degree of inflammation may be semi-quantified as a Limberg score, with a grade 0 score corresponding to a normal bowel wall with no thickening, no hyperemia, and well delineated mural stratification 36;
- grade 1: hypoechoic wall thickening, partially obscured mural stratification, absent mural flow
- blood flow assessed by color flow Doppler
- grade 2: wall thickening with intermittent (or "spot") increases in vascularity
- grade 3: wall thickening with protracted stretches of increased vascularity
- grade 4: color flow Doppler signals in both the bowel wall and surrounding mesenteric fat
On pulsed wave 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.
Complications may also be assessed with sonography, with the following features commonly detected in the following 37:
- abscess formation
- fistula creation
- linear, anechoic tract extending from an affected bowel loop to another structure, often with scattered hyperechoic puncta with inhomogeneous posterior acoustic shadowing (air)
- diameter of fistulous tract should be <2 cm 41
- luminal stenosis
- segmental wall thickening, loss of peristalsis, luminal narrowing or obliteration, preceding segment dilated (>2.5 cm)
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
- affected bowel loops separated by focal/regionally increased fat (fibrofatty proliferation; creeping fat)
- 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 ionizing 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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