large intestine

Question 1

In approximately 10% of cases, CD cannot
be distinguished from UC on clinical grounds

CD is a chronic inflammatory disorder that may involve
any part of the alimentary tract from the mouth to the anus but with a propensity for the distal small intestine and proximal colon.

In contrast, UC only affects the colon and rectum.

Answer 1

Inflammation in CD often is discontinuous along the longitudinal axis of the intestine and may involve all bowel layers
from mucosa to serosa, whereas in UC, inflammation starts in the rectum, is continuous, and is superficial, only affecting the epithelial layer of the mucosa

Question 2

Affected persons with CD
usually experience diarrhea and abdominal pain, frequently
accompanied by weight loss. Patients with UC will often experience bloody diarrhea with urgency. CD, in distinction to
UC, may manifest unique complications such as strictures and
fistulas, which often necessitate surgery.

Answer 2

The current hypothesis is that CD and UC result from
overly aggressive T-cell mediated immune responses to specific
components of the intestinal microbiota in genetically susceptible
individuals, and that disease expression is triggered by additional
environmental factors

Question 3

relative risk among first-degree relatives of subjects with IBD is 8
to 10 times higher than that of the general population.
32
Roughly
1 in 5 patients with CD report having at least one affected relative.

Answer 3

Very early onset IBD (VEOIBD) refers to children diagnosed with IBD before the age of 6 years.

Oral contraceptive pills have also been implicated with the development of CD, particularly among smokers.82
In addition, NSAIDs
have been associated with the development of IBD, and may trigger flares

Question 4

Depression is the

most commonly associated psychologic condition,

Answer 4

Many infectious agents have been proposed as the cause of CD, including Mycobacterium paratuberculosis, chlamydia, Listeria monocytogenes, cell-wall-deficient Pseudomonasspecies, reovirus, and many others

Mycobacterium
avium subspecies paratuberculosis(MAP) has been implicated as
an etiologic agent in CD.

Question 5

CD

Smoking
Risk in Caucasians
and Middle Eastern
immigrants

Antibiotic use in childhood
Risk in Caucasians,
protective in Asians/
Middle Eastern
immigrants

Breastfeeding
Protective in Asians
and most studies in
Caucasians

Oral contraceptives
Risk in Caucasians

Appendectomy
Risk in Caucasians

Low levels of vitamin D
Risk in Caucasians

Tea or coffee consumption
Risk in Caucasians

Answer 5

UC

Smoking
Protective in
Caucasians
and Asians

Antibiotic use in childhood
Risk in Caucasians,
protective in Asians/
Middle Eastern
immigrants

Breastfeeding
Protective in Asians
and most studies in
Caucasians

Oral contraceptives
Inconclusive

Appendectomy
Protective in
Caucasians

Low levels of vitamin D
Risk in Caucasians

Tea or coffee consumption
Protective in Asians

Question 6

Hygiene hypothesis:
Having pets in childhood, living on a farm, larger family size,
and drinking unpasteurized milk were inversely associated
with the risk of CD and UC.

Answer 6

Changing diet:
Introduction of packaged food, fast food chains, increased
use of antibiotics, increased fat (monounsaturated and
polyunsaturated fatty acids) consumption and sugar intake,
and less dietary fiber is associated with risk of IBD.

Dietary chemicals:
Food additives—saccharin, sucralose, carboxymethycellulose and polysorbate-80, and common emulsifiers (including
polysorbates, sorbate esters, lecithin) might increase risk
of IBD (data are derived from animal models).

Question 7

In IBD, breaches in a well-regulated mucosal immune system lead to chronic, uncontrolled mucosal inflammation

Intestinal epithelial cells are the first line of defense of the mucosal immune system

Patients with UC have an increased turnover rate of
colonic epithelium

the mucus layer in UC appears to
be thinner than normal.

Answer 7

Focal intestinal inflammation is the hallmark pathologic finding in CD

The earliest characteristic lesion of CD is the aphthous erosion

These superficial breaks in the mucosa are minute, range in size from barely visible to 3 mm, and are surrounded by a halo of erythema. In the small intestine, aphthae arise most often over lymphoid aggregates, with destruction of the overlying M cells. Aphthae represent focal areas of immune
activation.

Question 8

Noncaseating
granulomas, like aphthae are believed to be an early finding.
Estimates of the prevalence of granulomas

Answer 8

The granulomas of CD are sarcoidlike, consisting of collections of epithelioid histiocytes and a mixture
of other inflammatory cells, including lymphocytes and eosinophils; giant cells occasionally are seen. The granulomas usually are sparse, scattered, and not well-formed.

In contrast to the granulomas of TB, there is little or no central necrosis, and acid-fast stains and mycobacterial cultures are negative.

Question 9

Linear or serpiginous ulcers can form when
multiple ulcers fuse in a longitudinal direction. The classic cobblestoned appearance of CD results when linear and transverse
ulcers intersect and networks of ulcers surround areas of relatively normal mucosa with prominent submucosal edema.

Answer 9

Ulcers also can extend down to the muscularis propria

CD is a transmural process, in contrast to the more superficial inflammation of UC.

Question 10

The presence of lymphoid aggregates in the submucosa
and external to the muscularis propria is a reliable sign of CD
even when granulomas are not seen. Lymphoid aggregates occasionally may be seen within the muscularis propria, most often
adjacent to the myenteric plexus

Answer 10

Large ulcers, sinus tracts, fistulae, and strictures are late features of CD. Sinuses and fistulas represent extensions of fissures;
sinus tracts end blindly, and fistulas enter epithelial-lined organs
such as bowel, skin, bladder, or vagin

Question 11

At the anatomic level, one of the most characteristic findings of
CD is the presence of fat wrappingor creeping fat, a term that
refers to the edging of mesenteric fat onto the serosal surface of
the bowel.

Answer 11

At the microscopic level, the finding of pyloric metaplasia in
the terminal ileum, normally a response to peptic ulcer disease
when found in the duodenum, suggests a diagnosis of CD

Question 12

UC appears hyperemic, edematous, and granular in mild disease. As disease progresses, the
mucosa becomes hemorrhagic, with visible punctate ulcers.
These ulcers can enlarge and extend into the lamina propria.

Answer 12

They are often irregular in shape with overhanging edges or may
be linear along the line of the teniae coli

long-standing UC is atrophic and featureless
colonic mucosa, which is associated with shortening and narrowing of the colon. Patients with severe disease can develop acute
dilatation of the colon, also characterized by thin bowel wall and
grossly ulcerated mucosa with only small fragments or islands of
mucosa remaining

Question 13

Cryptitis is associated with discharge of mucus from
goblet cells and increased epithelial cell turnover.

Epithelial cells
undergoing regenerative changes become cuboidal with eccentric, large nuclei, and prominent nucleoli; these features may be
confused with dysplasia.

Answer 13

A classic histologic feature of chronic quiescent UC is crypt architectural distortion or actual dropout of glands

Another characteristic feature of chronic quiescent UC is Paneth cell metaplasia, with Paneth cells being located distal to the hepatic flexure, where they
normally are absent.

Question 14

In contrast to CD, continuous and symmetric involvement is the hallmark of UC (Fig. 115.8), with a sharp transition between diseased
and uninvolved segments of the colon.

Answer 14

Second, up to 75%
of patients with left-sided UC have peri-appendiceal inflammation
in the colon and patchy inflammation in the cecum,
156
resembling
the skip pattern characteristic of CD. Also, UC can be associated
with “backwash” ileitis, which can be observed in patients with
pancolitis or PSC.

Question 15

These patterns of rectal sparing, skip
lesions, and backwash ileitis can lead to a misdiagnosis of CD.

CD has a predilection for the distal small intestine and proximal colon.

Answer 15

Abdominal pain is a
more frequent and persistent complaint with CD than with UC. Pain is attributable to inflammation, abscess, or obstruction and
may be intermittent and colicky or sustained and severe.

Question 16

Common
symptoms for patients with UC include urgency, rectal bleeding,
diarrhea, passage of mucus, tenesmus, and abdominal pain. In more
severe cases, fever and weight loss may be prominent

Answer 16

Patients with CD

have a longer mean time to diagnosis than do patients with UC,

Question 17

A prodromal period is common in CD, though not typically seen in UC. This period might contribute to a delayed diagnosis, as does a prior diagnosis of IBS and older age at onset of
symptoms.

Answer 17

CD, inflammation of the ileum, often accompanied by involvement of the cecum, can manifest insidiously

The most typical presenting symptom
of colonic disease is diarrhea, occasionally with passage of obvious blood. Blood loss is not as common as with UC, although
can be severe in Crohn colitis

Perianal disease is another common presentation of CD.

In as many as 24% of patients with CD, perianal disease precedes intestinal manifestations, with a mean lead time of 4 years

Question 18

Skin lesions include maceration, superficial
ulcers, abscesses, and skin tags. Skin tags are generally of 2 types:
type 1 (“elephant ears”) are characteristically soft, nontender,
can be quite large, and typically not associated with underlying
anal pathology; and type 2, which often arise from healed fissures, ulcers, or hemorrhoids, are typically edematous, hard, and
tender

Answer 18

Anal canal lesions include fissures, ulcers, and stenosis. The anal fissures of CD tend to be located more eccentrically than the usual idiopathic fissures, which generally occur in
the midline

In most cases, an anal stricture is
asymptomatic,

Question 19

Upper GI tract CD is uncommon in the absence of disease beyond the ligament of Treitz

Answer 19

Patients with proximal CD tend to be younger at the time of diagnosis and
more often present with abdominal pain and malaise; they do not undergo surgery more often than do patients with lower tract disease alone, but the length of bowel that is resected tends to be greater

Question 20

Gastroduodenal CD manifests as Hp-negative PUD, with dyspepsia or epigastric pain as the primary symptom.

Answer 20

Clinical observation suggests that disease behavior in CD may be divided roughly into 2 categories: aggressive fistulizing disease and indolent stricturing disease

Question 21

presence of anti-Saccharomyces cerevisiaeantibody (ASCA), an antiglycan antibody to mannan (a constituent of the cell wall of baker’s yeast) correlates with small intestinal disease; identification
of anti-CBir1 (antiflagellin) is associated with internal penetrating and stricturing disease; and anti-Escherichia coliouter membrane porin C (anti-OmpC) predicts internal perforations

Answer 21

When perinuclear antineutrophil cytoplasmic antibodies (pANCA) are present in a patient with CD, the phenotype is often that of an inflammatory “UC-like” CD

Fistula formation is a frequent manifestation that results from the
transmural nature of CD.

Question 22

A classic presentation of CD is the onset of
an enterocutaneous fistula after appendectomy for what had been
presumed to be appendicitis.

Answer 22

he classic radiologic “string sign” of a markedly narrowed bowel segment amid widely spaced bowel loops
(Fig. 115.10) is a result of spasm and edema associated with active inflammation rather than fibrostenosis; the typical string
sign transiently resolves with administration of glucagon, which
relieves smooth muscle spasm

Question 23

Montreal Classification of CD is a proposed scheme
that incorporates the
patient’s age at diagnosis (A1, 16 years of age and younger; A2, 17 to 40 years of age; A3, older than
40 years of age); disease location (L1, ileal: L2, colonic; L3, ileocolonic); and disease behavior (B1, nonstricturing, nonpenetrating; B2, stricturing; B3, penetrating

Answer 23

The Montreal Classification of UC disease location is stratified by proctitis (E1, limited to the rectum), leftsided colitis (E2, up to the splenic flexure), and pancolitis
(E3, extending beyond the splenic flexure).

Question 24

Rectal bleeding is common in UC, and its characteristics are determined by the distribution of disease.

Answer 24

Patients with proctitis usually
complain of passing fresh blood, either separately from the stool or
streaked on the surface of a normal or hard stool.
This symptom often is mistaken for bleeding from hemorrhoids

Question 25

In contrast to
hemorrhoidal bleeding, however, patients with ulcerative proctitis
often pass a mixture of blood and mucus and might even be incontinent

Answer 25

When disease
activity is severe, patients typically pass liquid stool containing
blood, pus, and fecal matter.

Question 26

Diarrhea is the most common complaint among patients with IBD

The most important factor in weight loss, however, is poor oral intake. Most often, poor intake results from fear of eating (so-called sitophobia) because of postprandial abdominal pain or diarrhea.

Answer 26

With left-sided disease, distal colonic transit is rapid, but there is actual slowing of proximal transit,
which might help
explain the constipation that is commonly seen in patients with
distal colitis.

Question 27

Fever associated with active CD and UC usually is low grade
and occasionally is the presenting complaint, especially in
children;

Answer 27

Anemia is found in one-third of patients with CD, primarily as
a consequence of iron deficiency from blood loss. Macrocytic
anemia can result from vitamin B12
deficiency because of ileal
disease or resection, from SIBO or, less commonly, from folate
deficiency because of proximal small intestinal disease or sulfasalazine therapy.

Question 28

EIMs are found to occur more often in CD than in

UC and are more common among patients with colonic involvement than in patients with no colonic inflammation

Answer 28

Clubbing of the fingernails is a common and innocuous
EIM

arthritic manifestations, which are
observed more commonly in patients with CD than in those with UC

Question 29

2 types: pauciarticular (Type 1), in which the arthritis parallels disease activity in the bowel and typically involves fewer than 5 joints; and polyarticular (Type 2), in which the arthritis is independent of bowel activity and often involves more than 5 joints.

Answer 29

The most common skin lesions associated with IBD are pyoderma gangrenosum (PG) and erythema nodosum (EN).

PG appears first as a papule, pustule, or nodule. It can occur virtually anywhere on the body but most often it occurs on the leg or occasionally around a stoma, and progresses to an ulcer with
undermined borders

Question 30

The classic appearance of EN is a tender subcutaneous nodule with an erythematous or
dusky appearance, most often on the pretibial region

Answer 30

Episcleritis is more common in CD than in UC, consists of injection of the sclera and conjunctiva, and does not affect visual acuity.

Question 31

In contrast to the uveitis associated with ankylosing
spondylitis, the presentation of uveitis in patients with IBD often
is insidious, with bilateral involvement and extension to the posterior segment.

Answer 31

Cholelithiasis is seen most commonly in patients with CD with inflammation in the ileum or
resection of the ileum

PSC is genetically more correlated to UC than CD

Question 32

prothrombotic tendency has been noted in both CD and UC.
Patients may present with venous thromboembolism or, much
less commonly, arterial thrombosis

Answer 32

The most commonly associated

respiratory conditions are bronchiectasis and chronic bronchitis atients with IBD are more at risk to develop asthma

Question 33

IBD-unclassified (IBD-U), or
formerly “indeterminate” colitis, is diagnosed in approximately 5% to 10% of adult patients and up to 30% of pediatric patients;

Answer 33

ASCA (anti-Saccharomyces cerevesiaeantibodies) and pANCA (perinuclear antineutrophil cytoplasmic antibodies) were the first markers shown to correlate with the diagnosis of CD and UC, respectively

Question 34

Crohn Colitis

Depth of inflammation
Mucosal, submucosal, and transmural

Distribution
Often discontinuous and asymmetric, with skipped
segments of normal intervening mucosa,
especially in early disease

Fistulas
Perianal, enterocutaneous, rectovaginal,
enterovesicular, and other fistulas may be
present

Histopathology
Granulomas are present in 15%-60% of patients
(higher frequency in surgical specimens than in
mucosal pinch biopsies
Crypt abscesses may be present
Focally enhanced inflammation, often on a normal
background, is the hallmark

Ileum
Often involved (≈75% of cases) 

Mucosal lesions
Aphthae are common in early disease; late disease
is notable for stellate, rake, bear-claw, linear, or
serpiginous ulcers and cobblestoning

Perianal complications
Often prominent, including large anal skin tags,
deep fissures, perianal fistulas, that are often
complex

Rectum
Complete, or more often relative, rectal sparing

Serosal findings
Marked erythema and creeping fat (the latter is
virtually pathognomonic)

Strictures
Often present

Serology
pANCA in 20%-25%, ASCA in 41%-76%

Answer 34

Ulcerative Colitis

Depth of inflammation
Mucosal; transmural only in fulminant disease

Distribution
Continuous, symmetric, and diffuse, with
granularity or ulceration found in the entirety of
involved segments; however, periappendiceal
inflammation (cecal patch) is common, even
when the cecum is not involved

Fistulas
Absent, except for the rare occurrence of
rectovaginal or perianal fistula

Histopathology
Granulomas should not be present
(microgranulomas may be associated with
ruptured crypt abscess)
Crypt abscesses and ulcers are the defining lesion
Ulceration on a background of inflamed mucosa

Ileum
Not involved, except as backwash ileitis in pan-UC

Mucosal lesions
Micro-ulcers are more common, but larger ulcers
are seen
Pseudopolyps are more common

Perianal complications
Not prominent (fissure or fistula, if present, should
be uncomplicated)

Rectum
Typically involved with variable proximal
distribution; may appear normal if patient is
being treated with topical agents

Serosal findings
Absent except in severe colitis or toxic megacolon

Strictures
Rarely present; when present, suggests
adenocarcinoma

Serology
pANCA in 60%-65%, ASCA in 5%

Question 35

Patients with infectious colitis usually have a more acute onset of symptoms than do patients with a flare of IBD, and they have a prominence of abdominal pain; they also might report diarrheal illness in one or more of their contacts.

Answer 35

TB may mimic CD endoscopically
and involves the ileocecal location most commonly.

typical ulcer of TB runs parallel to the longitudinal axis of the bowel, in contrast to the ulcers of CD, which tend to orient perpendicular to the longitudinal axis of the bowel. TB is characterized by caseating granulomas as opposed to epithelioid granulomas, positive
Ziehl-Neelsen culture, and a positive tuberculosis PCR

Question 36

The colitis of E. coliO157:H7 is typically segmental and

involves the splenic flexure/descending colon

Answer 36

all patients with IBD who
present with a flare of disease activity should have C. difficile
excluded as a cause of the exacerbation

Question 37

Acute diverticulitis most commonly involves the sigmoid colon and does not involve the rectum

Answer 37

When the inflammation does extend to the rectum, it tends to
be patchy and involves only the proximal rectum. This appearance is more likely to be confused with CD than with UC. A
well-localized inflammatory process involving only the sigmoid
colonic segment associated with diverticulosis (SCAD)

Question 38

In CD, typical endoscopic
findings include discontinuous distribution of longitudinal ulcers
(defined as ≥4 cm), a cobblestoned appearance, and/or small aphthous ulcerations arranged in a longitudinal fashion.

Answer 38

Ischemic colitis usually occurs in older adults (see The classic distribution is segmental involvement in the
watershed areas around the splenic flexure or sigmoid colon but any area of the colon may be affected, and isolated involvement of the right colon and ischemic proctitis also have been described.

Symptoms of ischemic colitis usually resolve within 2 weeks, although colonoscopic abnormalities may take up to 6 months to resolve completely.

Question 39

Lack of rectal bleeding and laboratory markers of inflammation, as well as a normal
endoscopic and histologic appearance, help distinguish IBS from active IBD.

IBS symptoms are characterized by diarrhea in the morning in a
patient with IBD who has no laboratory values to suggest active
IBD.

Answer 39

level of calprotectin in a fecal sample.

The WBC count may be normal or elevated; an increased number
of band forms suggests the possibility of a pyogenic complication or active IBD.

Other markers of inflammation include fecal calprotectin or lactoferrin.

Question 40

suspected CD, ileocolonoscopy with biopsies from the terminal ileum as well as each colonic segment to look for microscopic
evidence of CD are first-line procedures to establish the diagnosis

Answer 40

Upper GI endoscopy should be performed in patients with
upper GI symptoms. Typical mucosal features recognized on
endoscopy in CD include aphthous erosions, stellate and other
discrete ulcers, mucosal edema, cobblestoning, and lumenal narrowing

The presence of well-demarcated lesions
on a background of normal mucosa is most easily recognized
in early or mild disease and is typical of CD. Rectal sparing is
more specific before treatment has been initiated.

Question 41

In patients with active flares
of disease, sigmoidoscopy is best performed in unprepared bowel
or with just tap water enemas so that the earliest signs of UC can
be detected without the hyperemia that is often present because of
preparative enemas. In patients diagnosed by sigmoidoscopy, colonoscopy should be performed to establish the extent of the disease
and to exclude CD after active disease has been controlled. colonoscopy is essential for CRC surveillance in
patients with longstanding disease or PSC.

Answer 41

The hallmark of UC is symmetric and continuous inflammation that begins at the anorectal junction where the anal squamous mucosa transitions to rectal columnar mucosa; inflammation extends proximally without interruption for the entire extent of disease

Question 42

The earliest endoscopic sign of UC is a decrease or loss of the normal vascular pattern, with mucosal erythema and edema, distortion or loss of vascular markings may be the only endoscopic evidence of UC in patients with quiescent disease.

With more severe inflammation, the mucosa may be covered by yellow-brown mucopurulent exudates associated with mucosal ulcerations.

Answer 42

severe UC is associated with friable mucosa that bleeds spontaneously, and, with diffuse colitis, there may be extensive areas of denuded
mucosa from severe mucosal ulcerations. Marked
edema can at times lead to narrowing of the lumen

Question 43

patients with long-standing UC, pseudopolyps may be
present. Inflammatory pseudopolyps develop in active disease and result from inflamed, regenerating epithelium that is interposed between ulcerations.

Answer 43

These inflammatory pseudopolyps may give
the colonic mucosa a cobblestoned appearance.

Endoscopically, pseudopolyps typically
are small, soft, pale, fleshy, and glistening; however, they may be large, sessile, or pedunculated and may have surface ulcerations.

Question 44

loss of normal colonic architecture with long-standing inflammation that is characterized by muscular hypertrophy, loss of the normal haustral fold pattern, decreased lumenal
diameter, and shortening of the colon; the resultant featureless
appearance of the colon in chronic UC gives rise to the lead-pipe
appearance seen on barium enema.

Answer 44

Strictures can occur in patients with chronic UC and result from focal muscular hypertrophy

Malignancy must be excluded in
patients with UC who have strictures, particularly long strictures without associated inflammation and strictures proximal to the splenic flexure

Question 45

Patients with severe UC should be evaluated for the presence of a
megacolon, by a plain film of the abdomen.

Answer 45

Radiologic findings that are significantly correlated
with endoscopic evidence of CD activity include mural enhancement
(segmental enhancement of all or part of the small intestinal
wall); increased density of peri-enteric fat (focal increased inhomogeneous
attenuation in the peri-enteric fat, compared with the
appearance of subcutaneous or peri-enteric fat in adjacent noninflamed
intestinal loops); and the comb sign (segmental dilatation
of the vasa recta involving an intestinal loop)

Question 46

Pelvic MRI is the preferred
imaging modality to evaluate suspected pelvic, perirectal or
perianal abscess or fistula in CD.

Answer 46

Remission is
widely accepted as a CDAI less than 150 and response to drug therapy
is defined as a decrease in CDAI ≥100 points

Question 47

The erythrocyte sedimentation rate and serum acute phase
response proteins (e.g., CRP) may be useful in tracking disease
activity, but lack sensitivity and specificity. High CRP levels are
indicative of active disease or an infectious complication. In addition,
there is a good correlation between clinical and endoscopic
disease activity in CD and CRP level

Answer 47

Fecal excretion of calprotectin
(a calcium- and zinc-binding protein found in neutrophils)
and of lactoferrin (an iron-binding glycoprotein secreted by most
mucosal membranes) have been shown to be sensitive markers of
intestinal inflammation295 that also might correlate with relapse
of quiescent disease and response to therapy with biologics