Keywords
Crohn's disease - computed tomography enterography - intestinal tuberculosis
Introduction
Crohn's disease (CD) and intestinal tuberculosis (ITB) are chronic granulomatous diseases
that due to their overlapping clinical, endoscopic, and pathological findings are
difficult to differentiate.[1]
[2]
The disease course of ITB is quite different from that of CD. ITB can be completely
cured if diagnosed early and treated properly. However, CD is prone to recurrences,
hence lies the importance of making accurate diagnosis at the earliest possible stage.[3]
[4]
Plain abdominal radiographs have little role in making a diagnosis of ITB or CD. Chest
radiograph may show features of active or healed tuberculosis in up to 15% of patients.[5]
Barium meal follow-through (BMFT) may show thickening of mucosal folds, ulcerations,
strictures, dilatation, and clumping of bowel loops in both these diseases and provides
information on bowel motility.[6]
[7] However, this study takes a long time, is two dimensional, and provides no extraluminal
information.
Barium enteroclysis has a higher sensitivity for detecting mucosal abnormalities and
strictures.[8]
[9] It achieves good distension of the small bowel loops to enable the detection of
early abnormalities. Its disadvantages include discomfort to the patient due to the
nasojejunal tube and active bowel distension, radiation and lack of information regarding
the bowel wall, and extraintestinal manifestations.
Ultrasonography (USG) is a simple and widely available modality without the effects
of ionizing radiation; however, it is not very useful in the differentiation of ITB
from CD. The other limitations include operator dependence, bowel gas, obesity, and
long scan times required for complete evaluation.
Computed tomography (CT) is often the initial investigation performed for the evaluation
of suspected bowel pathology. The positive contrast only depicts bowel wall thickening,
stricture, and dilatation, but not mucosal abnormality, and does not provide adequate
distension of the bowel. CT enteroclysis is performed after inserting a nasojejunal
tube and injecting neutral contrast agent to provide adequate distension of the small
bowel.[10] The tube and active bowel distension often causes discomfort to the patient.
CT enterography (CTE) combines the improved spatial and temporal resolution of multiple
detector row CT with large volumes of ingested neutral enteric contrast material to
permit visualization of the small bowel wall and lumen. CTE can image the entire gastrointestinal
tract and characterize extraintestinal manifestations, such as the lymph nodes, mesenteric
changes, mural stratification, fibrofatty proliferation, fistulae, abscesses, adjacent
organ involvement, and ascites that have an important role in differentiating CD and
ITB.
Magnetic resonance enterography (MRE) recently has been gaining in popularity, especially
for follow-up imaging of pediatric and young patients with established inflammatory
conditions of the small bowel.[11]
[12] The lack of ionizing radiation is an advantage of MRE over CTE, especially when
evaluating patients with known renal dysfunction. However, MRE is time consuming,
expensive, and has variable reproducibility regarding image quality as compared with
CTE.
Technique
Patients are requested to abstain from all food and drink for 4 hours prior to scanning.
Bowel is distended passively by ingesting neutral oral contrast agents, which include
water, polyethylene glycol solution, or VoLumen (low-density barium in sorbitol),
adding osmotic agents such as mannitol, sorbitol, or polyethylene glycol improves
bowel distension.[13]
[14] We used mannitol (20%) that is prepared by diluting 400 mL of mannitol in 1,500
mL of water. This solution is ingested over 45 minutes, and the patient is scanned
subsequently. The last 250 to 300 mL is ingested on table, just prior to scanning
for gastric distension, and the patient is made to lie in right lateral decubitus
for 3 to 5 minutes; 20 mg Buscopan is administered intravenously (IV) immediately
prior to scanning to reduce bowel peristalsis.[15] Scanning was done in enteral phase acquired at 45 seconds, and bowel wall shows
maximal enhancement in this phase[16] using 128-slice MDCT scanner (Philips Ingenuity, Suzhou, China) and 1.5 mL/kg of
iohexol (Omnipaque 350 mg/mL 50 mL, GE Health Care, Shanghai, China). Summary of technique[15] is mentioned in [Table 1].
Table 1
Summary of the technique
-
Withhold all oral intake 4 h prior to examination
-
1.5–2 L of oral neutral contrast (20% mannitol) given over 45 min, last 200–250 mL
ingested on table prior to scanning for gastric distension
-
20 mg Buscopan administered intravenously (IV) prior to scanning
-
1.5 mL/kg of Iohexol (max 150 mL) administered IV at 4 mL/s via 18-gauge cannula using
automated power injector
-
Scanning is performed from diaphragm to symphysis pubis. Images acquired at 45 s post-IV
contrast administration
-
128-slice multiple detector computed tomography (MDCT) scanner Philips Ingenia
-
Slice thickness 2 mm, reconstruction interval 0.75 mm
|
Postprocessing techniques include reformatting of axial image data for coronal, sagittal,
and maximum intensity projections.
Multiplanar reformatting of axial image data allows excellent demonstration and characterization
of enteric and extraenteric abnormalities.[17] Maximum intensity projection images are useful particularly for visualizing the
mesenteric vasculature.
Intestinal Tuberculosis
The incidence of extrapulmonary TB is 15 to 20%, with 3% affecting the abdomen including
the small bowel. Abdominal TB is the sixth most common extrapulmonary site of involvement.
Only 15% of patients with abdominal TB have evidence of pulmonary disease, and chest
radiography may be normal in 50 to 65% of these patients.[5]
[18]
ITB can be divided into three categories—ulcerative, hypertrophic, and ulcerohypertrophic—with
the ulcerative type being the most common. Manifestations depend on the host's immune
system. The ulcerative form occurs in patients with reduced immune response, where healing often results in the
formation of fibrotic strictures, especially if the ulcers are deep and circumferential.
The hypertrophic form consists of bowel wall thickening with scarring, fibrosis, and a rigid mass-like
appearance that mimics that of malignancies. The ulcero-hypertrophic form is a subtype with a combination of the features of the ulcerative and hypertrophic
forms.[19]
Imaging in the form of barium studies were the initial investigation for intestinal
TB, but in the past decade, CT scan and, recently, CTE have almost replaced barium
studies due to a better depiction of mural and extraintestinal involvement.
Abdominal tuberculosis may affect any part of bowel from the duodenum to rectum, but
the most frequent site of ITB is ileocecal area (~90% in case of gastrointestinal
TB). The sites of involvement in descending order of frequency are the ileocecal junction,
followed by the ileum, caecum, ascending colon, jejunum, rest of the colon, rectum,
duodenum, and stomach.[20]
Peritoneal TB is the most common form of abdominal TB and involves alone or in combination
with the peritoneal cavity, mesentery, and omentum. Three types of peritoneal TB are
described[21]
[22]: wet type with ascites or pockets of loculated fluid ([Figs. 1]
[2]); dry type with bulky mesenteric thickening and lymph adenopathy ([Fig. 3]); and third type with mass formation due to omental thickening that may be mistaken for a tumor.[21]
Fig. 1 Axial (A) and (B) CTE images in a 19-year-old-male patient with wet tubercular peritonitis who presented
with abdominal distension and fever for 1.5 months, showing mesenteric nodes (thin
arrow), ascites (thick arrow), and peritoneal enhancement.
Fig. 2 Axial CTE image in a 30-year-old man with TB peritonitis showing enhancing peritoneum
(arrow) encasing small bowel loops giving a clustered centrally in a cocoon-like appearance.
Fig. 3 Axial (A) and (B) CTE images in a 44-year-old man with abdominal discomfort and low-grade fever showing
mesenteric nodes (thin arrow) and peritoneal enhancement—DRY tubercular peritonitis.
Active ileocecal disease is characterized by circumferential wall thickening of terminal
ileum, ileocecal junction, and cecum with narrowed lumen ([Figs. 4]
[5]
[6]). Dilatation of the proximal bowel segment may be seen. Another predictor of active
inflammation is enhancement of mucosa or the entire wall. Intestinal wall thickening
is usually homogeneous without stratification. Wall stratification seen in CD results
from contrast enhancement of mucosa and muscularis, with hypodense edema of submucosa
causing a layered appearance.
Fig. 4 Axial (A), coronal (B), and sagittal (C) CTE images in a 30-year-old patient with ITB showing gross thickening of cecum (arrow)
ileocecal junction (arrowhead) with dilatation of terminal ileum (X).
Fig. 5 Axial (A) and coronal (B) CTE images in a 26-year-old woman with low-grade fever and weight loss showing thickening
and contraction of cecum (arrowhead) with pericecal fat stranding and gross thickening
of ileocecal valve (arrow) consistent with ITB.
Fig. 6 Ileocecal Koch's: Oblique coronal reconstruction through the abdomen in the venous
phase of a 25-year-old woman with fever and weight loss shows a contracted cecum (arrowhead)
and significantly thickened, heterogeneously enhancing terminal ileum and ileocecal
junction without wall stratification (arrow) suggestive of TB. Necrotic nodes are
seen just above the arrowhead. Ascitis with tiny peritoneal nodules are seen just
lateral to the arrowhead.
Healing results in short-segment strictures that are seen as short segments of wall
thickening without wall enhancement or stratification with proximal bowel dilatation.[20] Ileocecal valve may also become scarred with stricture and subsequent dilatation
of the terminal ileum, which rarely may become patulous with loss of valve function.
Usually, the segment of involvement is single in ITB, infrequently multiple segments
of involvement may also be seen when differentiation from CD is difficult. Isolated
segmental colonic involvement may be seen in 10% of abdominal tuberculosis, with sigmoid,
ascending, and transverse colon being common sites.
Other complications include vascular complications, intussusception, and obstruction
of the small bowel.[20]
Extraintestinal changes include mesenteric nodal enlargement that may occur as discrete
nodes or conglomerate nodal masses. Enlarged nodes are often necrotic, which helps
in making an accurate diagnosis ([Fig. 7]). On healing, the nodes may disappear or may show calcification. Perienteric and
mesenteric fat stranding is uncommon. Omental or peritoneal thickening may be seen
with omentum showing nodularity or smudgy pattern of enhancement. There may be associated
abdominal cocoon ([Fig. 2]), developing due to thin film of fibrosis encasing the bowel loops that appear clumped.
This is seen on CTE or MRE as an area of clumped, often dilated, small bowel loops
with thin hypodense or hypointense capsule around it. In long-standing cases, there
may be proliferation of surrounding fat, although infrequently. Associated involvement
of other organs such as the liver, spleen, or peritoneum also helps in making a diagnosis
([Fig. 8]).[23]
Fig. 7 Axial (A), coronal (B), and axial (C) CTE images in a 38-year-old man with ileocecal TB showing thickening of cecum and
ileocecal junction (arrowhead) with enlarged necrotic nodes (arrows) and axial (D) CT chest image shows multiple centrilobular nodules in bilateral lung fields giving
a tree in bud apprearance
Fig. 8 Hepatic perit spleen Koch's: Oblique coronal reconstruction through the abdomen in
the venous phase of a 68-year-old diabetic man with pulmonary TB. (A) Several tiny hepatic nodules (arrowheads), peritoneal thickening (curved arrow),
and coalescent necrotic retroperitoneal nodes (straight arrow). (B) Multiple small splenic hypodense nodules (arrowhead). Some of these nodules have
coalesced to form a sinus leading to the perisplenic region and lateral abdominal
wall (arrow).
Crohn's Disease
CD is characterized by chronic, transmural, often granulomatous, and intestinal inflammation.
The small bowel is involved in almost 80% of the cases, with the ileocecal region
affected in 50%.[24] Enteric involvement of CD tends to be transmural, segmental, and usually discontinuous
also known as skip lesions
[16] ([Fig. 9]). Small bowel disease is multifocal with areas of different activity, some areas
with acute inflammatory, and others with fibrostenosing disease ([Fig. 10]).
Fig. 9 Active Crohn's disease in a 45-year-old woman. Axial (A), axial (B), and coronal (C) CTE section Multifocal involvement mucosal hyperenhancement (red arrow) and mural
stratification (yellow arrow) of the terminal ileum. Coronal CTE image shows mesenteric
hypervascularity (arrowheads) adjacent to the involved bowel segment, indicating active
Crohn's disease.
Fig. 10 Fibrostenosing Crohn's disease in a 32-year-old man. Axial and coronal CTE image
shows a segmental stricture involving proximal ileal loop. Homogenous mural thickening
is seen at the strictured segment without mural hyperenhancement, suggesting fibrostenotic
disease (arrow).
CD has been classified into four stages that help in planning therapy[25]: (1) active inflammatory, (2) fibrostenotic, (3) penetrating, and (4) reparative
or regenerative subtypes. Active inflammation shows various features on imaging, as
ulceration and mucosal enhancement. Fibrostenotic disease suggests a healing phase
due to collagen deposition and stricture formation. Penetrating disease occurs due
to the extension of deep ulcers, resulting in extraintestinal inflammation, abscesses,
sinuses, and fistulas. Often, multiple stages coexist in the same patient or bowel
segment.[25] Similar to ITB, the ileocecal region is the most common site of involvement. Involvement
of multiple segments with normal intervening bowel segment is typically seen, but
this alone may not be specific.
CD has a variety of appearances at CTE depending on disease activity and associated
complications such as fistula or abscess. On CTE, enteric findings such as mural hyperenhancement,
bowel wall thickening, mural stratification and extraenteric findings such as engorged
vasa recta (“comb sign”),[26] and increased attenuation of the mesenteric fat are features of active inflammatory
small bowel CD[26]
[27] ([Figs. 11]
[12]
[13]). Among these findings, combination of mural hyperenhancement and bowel wall thickening
is the most sensitive CTE findings suggesting the active inflammatory CD.
Fig. 11 Active Crohn's disease in a 20-year-old man. Axial CTE section shows mucosal hyperenhancement
(black arrow) and mural stratification (white arrow) of the terminal ileum, an appearance
that contrasts markedly with that of nondiseased ileal segments (X). Axial (A) and coronal (B) CTE image shows mesenteric hypervascularity (comb sign) (arrowhead) adjacent to
the involved bowel segment, indicating active Crohn's disease.
Fig. 12 Axial CTE section shows mucosal hyperenhancement and mural stratification of the
terminal ileum. Axial (A) and coronal (B) CTE image shows mesenteric hypervascularity (arrow), comb sign, adjacent to the
involved bowel segment indicating active Crohn's disease.
Fig. 13 Crohn's stricture: Oblique coronal reconstruction through the abdomen in the venous
phase of a 56-year-old man, with symptoms of recurrent subacute intestinal obstruction
showing a stricture (arrow) with wall stratification and intense enhancement of the
mucosa suggestive active inflammation.
Mural enhancement is the most sensitive indicator of active CD[28]; therefore, bowel loops with similar distension should be compared as both the jejunum
and normal collapsed loops may demonstrate regions of higher attenuation simulating
enhancement.
A mural attenuation threshold of 109 HU and an abnormal to normal loop enhancement
ratio of >1.3 have been used to objectively correlate mural hyperenhancement and bowel
wall thickness with disease activity on CTE and highly correlated with histologic
findings of active disease. Visual assessment, however, presents higher specificity
than quantitative measurements.[29]
The term mural stratification denotes the visualization of bowel wall layers at CT after administration of IV contrast)[28]
[30]
[31] ([Fig. 12]). Bilaminar mural stratification refers to mucosal hyperenhancement and decreased
intramural attenuation, and trilaminar mural stratification refers to alternating
areas of high and low attenuation due to mucosal and serosal hyperenhancement and
low intramural attenuation. The low intramural attenuation can represent edema, inflammatory
infiltrate, or fat. Mural stratification due to intramural edema is more indicative
of active disease compared with a homogenously enhanced wall,[32] whereas the presence of intramural fat indicates chronic process.[27]
In active CD, increased attenuation of the mesenteric fat is often seen due to edema
or prominence of vasa recta. Prominence of the vasa recta is known as the “comb sign.”[26]
[33] This sign, along with increased mesenteric fat attenuation, is the most specific
CT feature of active CD.[34] Findings suggestive of chronicity in CD include submucosal fat deposition, pseudosacculation,
surrounding fibrofatty proliferation, and fibrotic strictures. Inflammatory involvement
of the mesenteric border of the affected bowel segment with associated asymmetric
fibrosis and pseudosacculation of the antimesenteric border is a hallmark.[16]
The transmural inflammation with increased intraluminal pressure proximal to the site
of strictures may lead to extension of the inflammatory process across the serosal
surface into the adjacent mesentery or structures, resulting in extraenteric complications
as fistula, sinus tract, and abscess. CTE has an important role in the evaluation
of extraenteric complications of CD[25]
[35] ([Figs. 14]
[15]).
Fig. 14 Crohn's disease in a 34-year-old woman. (A) Axial and (B) coronal CTE image shows enteroenteric fistula involving ileal loops (arrow) with
adjacent fat stranding.
Fig. 15 Fistulizing Crohn's: axial sections through the abdomen in the venous phase of a
43-year-old man show a radiating pattern of fistulae connecting adjacent small bowel
loops in panel A. The outline of the fistulae has been drawn in panel B.
CTE has high sensitivity for the detection of bowel strictures occurring as a complication
of CD. Reversible strictures are characterized by mucosal hyperenhancement, mural
stratification, fat stranding, and engorgement of the vasa recta; however, transmural
fibrosis may result in a lack of enhancement and loss of stratification.[16] It is important to differentiate between active and fibrotic strictures ([Fig. 8]) because the former warrants medical management whereas the latter may require surgical
intervention.[35]
Extraenteric findings such as cholelithiasis, urolithiasis, and sacroiliitis are also
picked up on CT.[36]
Radiologic features are helpful in differentiating ITB from CD.[1]
[37] These differences are presented in [Table 2].
Table 2
Differentiating features of ITB and CD
|
Features
|
ITB
|
CD
|
|
Abbreviations: CD, Crohn's disease; ICJ, ileocolic junction; ITB, intestinal tuberculosis.
|
|
Site of involvement
|
ICJ with terminal ileum
|
Terminal ileum
|
|
Length of involvement
|
Short segment
|
Long segment
|
|
Wall thickness
|
<6 mm
|
>6 mm
|
|
Skip lesions
|
Uncommon
|
Common
|
|
Mural hyperenhancement
|
Rare
|
In active CD
|
|
Mural stratification
|
Uncommon
|
Common
|
|
Interbowel fistula
|
Rare
|
Common
|
|
Mesenteric abscess
|
Rare
|
Common
|
|
Increased mesenteric vascularity
|
Uncommon
|
Common (comb sign)
|
|
Ascites
|
Frequent
|
Uncommon
|
|
Peritoneal thickening
|
Often associated
|
Uncommon
|
|
Omental caking, nodularity
|
Frequent
|
Rare
|
|
Mesenteric nodes
|
Large (>1 cm), necrotic
|
Small, homogenous
|
Radiologic investigations provide useful clues to aid diagnosis, but their major role
is in assessing the extent of the disease.[38]
Endoscopy plays an important role in diagnosis.[39]
[40] Apart from visual inspection, mucosal biopsy can be obtained for histopathology,
culture, and molecular tests. CD patients usually have longitudinal ulcers, cobblestone
appearance of mucosa, and anorectal involvement.[41] Transverse ulcers, patulous ileocecal valve, and involvement of fewer of colonic
segments are commoner in ITB.
ITB and CD are both chronic granulomatous diseases with subtle histologic differences
between them. Histologic features suggesting ITB include confluent granulomas, multiple
granulomas, large granuloma size, bands of epithelioid histiocytes lining ulcers,
submucosal granulomas, and disproportionate submucosal inflammation, that is, submucosal
inflammation that significantly exceeds mucosal inflammation. Although caseation and
necrosis in granulomas or positive stain for acid-fast Bacillus (AFB) is virtually
diagnostic for ITB, the problem is the poor yield of endoscopic sampling, which is
diagnostic in <30% of cases. Features seen more frequently in CD include microgranulomas,
nonconfluent granulomas, single granulomas as the only foci of granulomatous inflammation,
and architectural distortion distant from granulomatous inflammation.[1]
Conclusion
CTE is a valuable tool for differentiating ITB from CD. It helps in making a diagnosis,
defining the extent of disease, and assessing the presence of active inflammation
and complications. Although overlapping findings occur with ITB, a combination of
findings helps us differentiate between the two.
