Everybody Loves Sanofi’s Giant Human Colon
20-foot long, walk-through model of a human colon in NYC’s Times Square
Anathomy
• The ascending colon,
descending colon, rectum,
and posterior surface of the
hepatic and splenic flexures
are fixed retroperitoneal
structures.
• The cecum, transverse
colon and sigmoid colon are
intraperitoneal and are
prone to volvulus because
of their location and relative
lack of fixation.
Anathomy
• The longitudinal muscle
is an incomplete layer and
is seen as three bands of
muscle, called teniae coli,
located 120 degrees apart
around the circumference
of the colon.
• Haustra coli are
sacculations between the
teniae and are separated
by crescent-shaped folds
called plicae semilunares.
Sympathetic nerves inhibit and
parasympathetic nerves stimulate
peristalsis.
Macro- and Micro• The colonic wall consists of
mucosa, submucosa, inner
circular muscle, outer
longitudinal muscle and
serosa .
• The colonic mucosa is
similar in organization to
the small intestine mucosa
except that it lacks villi.
• There is no serosal layer in
the rectum.
Definition
• Irritable bowel syndrome (IBS) is characterized by
altered bowel habits and abdominal discomfort in the
absence of organic disease.
• No clear diagnostic markers exist for IBS; thus, all
definitions are based on the clinical presentation.
• The Rome II criteria for the diagnosis of IBS include at
least 3 months of continuous or recurrent abdominal
pain or discomfort that has two of the following
features: relief by defecation, association with a
change in the frequency and a change in stool form
ROME II DEFINTION
• Symptoms that cumulatively Support the Diagnosis of
Irritable Bowel Syndrome:
– Abnormal stool frequency (> 3 bowel movements/day and less
than 3 bowel movements per week);
– Abnormal stool form (lumpy/hard or loose/watery stool);
– Abnormal stool passage (straining, urgency or feeling of
incomplete evacuation);
– Passage of mucus;
– Bloating or feeling of abdominal distension
DEFINITION -LIMITS• Symptoms based definition due to the absence of
a specific biologic “marker”.
• Overlap between the definition of irritable bowel
syndrome and other functional disorders.
• The present definition are not able to differentiate
between the subgroups of IBS patients.
• The present definition criteria seem to have a
different gender sensibility.
SYMPTOMS BASED DEFINITION
Functional gastrointestinal
disorders - a frequent cause
for referral to
gastroenterologist
Epidemiology
- Prevalence: 10%-20% (5 and 65%)
- more frequent in women (2:1);
- all age affected
- 20 - 30% presented to doctor
- 1%-3% - GP consultation
Etiology
PATHOPHYSIOLOGY
-MECANISMS• Digestive motility
disorders;
• Visceral hypersensibility;
• Involvement of intestinal
infection;
• Alimentary intolerance
and allergy;
• Alteration of perception
due to psychiatric
disorders.
PATHOGENIC MECANISMS
- Intestinal hypersensibility -
Microscopy
• irritable bowel syndrome
does not involve intestinal
inflammation
• Research suggests that
neuronal degeneration and
myenteric plexus
lymphocytosis may exist in
the proximal jejunum.
• Additionally, colonic
lymphocytosis and
enteroendocrine cell
hyperplasia have been
demonstrated in some
patients.
Symptoms
Gastrointestinal Symptoms
• abdominal pain
• alteration in bowel habits
• alteration in bowel habits
Extraintestinal Symptoms
• chronic pelvic pain
• genitourinary dysfunction
• chronic fatigue syndrome
• co-morbidities
Abdominal pain
• According to the new Rome II criteria,
abdominal pain or discomfort is a prerequisite
clinical feature of IBS.
•
•
•
•
hypogastrium 25%
the right side 20%
the left side 20%
the epigastrium 10%
Abdominal pain
• Is generally crampy or achy, although sharp, dull,
gaslike or nondescript pains.
• It may be mild enough to be ignored or it may
interfere with daily activities.
• Defecation may provide temporary relief from
the pain of IBS, while meal ingestion may
exacerbate the discomfort usually 60 to 90
minutes postprandially.
• Pain that is progressive, prevents sleep, leads to
anorexia or inability to eat or is associated with
weight loss warrants exclusion of organic
disease.
Alteration in bowel habits
• constipation, diarrhea or constipation alternating
with diarrhea
• long periods of straining may be required for fecal
evacuation both in constipation- and diarrheapredominant patients
• constipation can persist for weeks to months,
interrupted by brief periods of diarrhea
• feelings of incomplete fecal evacuation may lead
to multiple attempts at stool passage daily
Alteration in bowel habits
• In diarrhea-prone patients, stools
characteristically are loose and frequent but of
normal daily volume.
• Generally, diarrheal stools occur only during
waking hours, often early in the day and an
urgent desire to defecate after a meal is
reported by 36% of patients.
• Fecal urgency and loose stools may develop
during stress.
Alteration in bowel habits
In a 12-week trial study of 59 patients with IBS, Hahn and
colleagues 38 found that the population reported pain
or discomfort on 50% of days.
• on 33% of days bloating was reported
• altered stool formation and passage were found,
respectively, on 25% and 18% of days
• for more than half of the study period 50% of the
patients had at least one symptom
• The symptoms lasted on average for 5 days or less,
although pain/discomfort and bloating tended to last
the longest.
Gas and Flatulence
• Patients with IBS frequently complain of abdominal
distention and increased belching or flatulence, all of
which they attribute to increased gas.
• Quantitative measurements reveal that most patients
who complain of increased gas generate no more than
a normal amount of intestinal gas.
• Studies have shown that most IBS patients have
impaired transit and tolerance of intestinal gas loads.
• In addition, patients with IBS tend to reflux gas from
the distal to the more proximal intestine, which may
explain the belching.
Bloating
Alteration in bowel habits
Symptoms not associated with IBS that
warrant exclusion of organic disease include:
•
•
•
•
nocturnal diarrhea
rectal bleeding
malabsorption
weight loss
Upper gastrointestinal symptoms
(25 and 50%)
•
•
•
•
dyspepsia
heartburn
nausea
vomiting
• IBS symptoms are prevalent in noncardiac
chest pain patients, suggesting overlap with
other functional gut disorders
Extraintestinal symptoms
• Patients with functional gut disorders visit primary care
physicians three times as often for nongastrointestinal
problems as do healthy persons and undergo more
appendectomies and hysterectomies.
• chronic pelvic pain
• genitourinary dysfunction:
- dysmenorrhea
- dyspareunia
- impotence
- urinary frequency
- nocturia
- a sensation of incomplete bladder emptying
Extraintestinal symptoms
• IBS symptoms are found in 42% of patients with
fibromyalgia.
• 63% of patients with chronic fatigue syndrome
• higher incidences of peptic ulcer disease,
hypertension, low back pain, headaches, and
rashes than the general population and more
commonly report fatigue, loss of concentration,
insomnia, palpitations and unpleasant tastes in
the mouth
COMORBIDITY
• About 50% of IBS patients from primary care and gastroenterology
clinics have at least one comorbid somatic symptom.
• Comorbidity substantially alters the quality of life of IBS patients
and adds an additional cost for its treatment.
• The presence of commorbidity was suggested to be a new
diagnostic criterion.
• Specific comorbide somatic condition are Fibromyalgia, Chronic
fatigue syndrome, Chronic pelvic pain, Temporo-mandibular joint
disorder.
• Overlap with other functional gastrointestinal disorders: functional
dyspepsia, non-cardiac chest pain, functional ano-rectal pain, fecal
incontinence.
COMORBIDITY
• Overlap with psychiatric
disorders such as:
- depressive syndromes
- anxiety disorder
- somatisation
Figure 5.33 - Visceral sensations
©Copyright Science Press Internet Services
Alarm signs
- onset in elderly
– increasing intensity
– waking up the patient
– fever
– weight loss
– rectoragia
Physical findings
• The physical examination of the patient usually is
normal
• Abdominal compression may elicit tenderness
that is vague and poorly localized.
• Tender bowel loops are commonly palpable.
• Masses, adenopathy, hepatosplenomegaly,
ascites, blood in the stool or autonomic or
peripheral neuropathy are suggestive of organic
disease and are not consistent with IBS.
Diagnosis
• Confident diagnosis of IBS relies on recognition of
characteristic symptom profiles as well as the
detection of alarm findings (weight loss, bleeding,
fever, or palpable masses) which are more suggestive
of organic disease.
• The symptoms that define IBS also are prominent
complaints of many other conditions including
malignancies, inflammatory diseases, infections, and
ischemic diseases of the gastrointestinal tract as well as
some nongastrointestinal conditions.
In a questionnaire survey, Manning and
colleagues defined four symptoms that were
significantly more common in IBS than organic disease
1.
2.
3.
4.
relief of abdominal pain upon defecation
looser stools with onset of pain
more frequent stools with the onset of pain
abdominal distention
Differential diagnosis
•
Abdominal Angina
Hypothyroidism
Anxiety Disorders
Inflammatory Bowel Disease
Bacterial Overgrowth Syndrome
Lactose Intolerance
Malignant Neoplasms of the Small Intestine
Celiac Sprue
Colon Cancer, Adenocarcinoma
Endometriosis
Food Allergies
Postcholecystectomy Syndrome
Gastroenteritis
Giardiasis
Ulcerative Colitis
Hyperthyroidism
•
Fructose intolerance
Gastrinoma
Infectious colitis
Medication adverse effects
Secretory diarrhea
VIPoma
•
Functional bowel disorders
Functional abdominal bloating
• This is characterized by symptoms of
abdominal fullness or distension, awareness
of audible bowel sounds and excessive flatus
with no evidence of either maldigestion and
malabsorption or excessive consumption of
poorly absorbed fermentable carbohydrate.
Functional constipation
• This is arbitrarily defined as either persistently
difficult, infrequent defaecation or the
sensation of incomplete defaecation.
• Usually, two or more of the following are
present: straining at defaecation; lumpy or
hard stools; the sensation of incomplete
evacuation; two or fewer bowel movements
per week.
Functional diarrhea
• This is defined as the frequent passage of
unformed stool without the presence of other
features of irritable bowel syndrome.
• Neither abdominal pain nor the frequent passage
of formed stools are included in the symptoms.
• The diagnosis of functional diarrhoea depends on
the presence of two or more of the following:
unformed stool; three or more bowel movements
per day; increased stool weight, greater than 200
g/day.
Functional abdominal pain
• The relationship between the abdominal pain and a
disturbance of gastrointestinal-tract function is difficult
to ascertain.
• Abdominal pain is frequent, recurrent or continuous,
and characteristically persists for many months.
• The relationship between pain and recognizable
physiological events such as eating, defecation or
menstruation is lacking and evidence of organic
disease in the abdomen is absent.
• Most of these patients show a major loss of daily
functioning capacity and exhibit chronic illness
behaviour.
Investigations
• Laboratory
• Imaging studies
• Procedures
Laboratory
• Cell blood count (anemia, inflammation, infection)
• Metabolic panel (metabolic disorders,
dehydration/electrolyte abnormalities)
• Hemoccult test
• H2 breaths (bacterial vergrowth)
• Microbiologic studies
-
Ova and parasites (Giardia antigen)
Enteric pathogens
Leukocites
Clostridium difficile toxins
Imaging studies
• Upper GI barium study with small bowel followthrough: Screen for tumor, inflammation,
obstruction and Crohn disease.
• Double-contrast barium enema: Screen for
neoplasm and inflammation.
• Abdominal ultrasonography: Consider this test if
the patient has recurrent dyspepsia or
characteristic postprandial pain.
• Abdominal CT scan: Screen for tumors,
obstruction and pancreatic disease.
Colon spasm
irregular shapes of the intestines
©Copyright Science Press Internet Services
Other tests
• Direct a lactose-free diet for 1 week in conjunction
with lactase supplements. Improvement incriminates
lactose intolerance, although the patient's clinical
history and response to a trial may be unreliable.
Therefore, some gastroenterologists recommend a
formal hydrogen breath test. Fructose intolerance must
also be considered.
• Direct a 48-hour fast. Persistent diarrhea suggests a
secretory etiology.
• Anal manometry may reveal spastic response to rectal
distention or other problems.
Anorectal manometry
• Anorectal manometry catheter
• Distal balloon 320 ml
Procedures
• Endoscopy directed for many patients with irritable bowel
syndrome includes flexible sigmoidoscopy to determine
inflammation or distal obstruction.
• Esophagogastroduodenoscopy with possible biopsy Indicated for a patient with persistent dyspepsia or if
weight loss or symptoms suggest malabsorption or if celiac
disease is a concern
• Colonoscopy - Indicated for patients with warning signs,
such as bleeding; anemia; chronic diarrhea; older age;
history of colon polyps; cancer in the patient or first-degree
relatives; or constitutional symptoms, such as weight loss
or anorexia. A screening colonoscopy should be performed
according to published guidelines.
Showing characteristic triangular folds of the transverse colon.
Conclusion
Prognosis
• Mostly good.
• Not usually serious or life-shortening
• IBS causes a great deal of discomfort and distress,
but it does not cause permanent harm to the
intestines and does not lead to intestinal bleeding
of the bowel or to a serious disease such as
cancer.
• Often IBS is just a mild annoyance, but for some
people it can be disabling.
Definition
• Inflammatory bowel disease (IBD) is an
idiopathic and chronic intestinal
inflammation.
• Ulcerative colitis (UC) and Crohn’s disease
(CD) are the two major types of IBD.
2
Specific IBD syndromes
•
•
•
•
•
Proctitis
Proctosigmoiditis
Left-sided ileitis
Ileitis
Ileocolitis
Epidemiology
24
Geographical distribution of IBD
(reproduced with permission, the AGA Teaching Project, 1992)
25
Ethnic prevalence of IBD
50
40
Prevalence
(per 105)
30
20
10
0
White
Whites
(after Kurata et al, 1992)
Black
Blacks
Hispanic
Bedouin
Arabs
Asian
Hispanics Other
Asians
Ethnic Group
Incidence of IBD with respect to age
and sex
(reproduced with permission from Wells Medical Ltd, Binder 1993)
26
Patterns of IBD incidence in previous
decades
(reproduced with permission from Wells Medical Ltd, Binder 1993)
27
28
Etiological theories of IBD
•
•
•
•
•
•
Genetic
Smoking
Dietary
Infection
Immunological
Psychological?
Recent controversies in the
pathogenesis of IBD
• Genetics
• Mycobacterium paratuberculosis
• Measles virus
29
30
Genetic factors
• It is estimated that between 10 and 20 genes
are involved
• Susceptibility loci have been located on
chromosomes 3, 7, 12 and 16
• The genetic contribution to the aetiology of
both Crohn’s disease and ulcerative colitis is
polygenic NOT Mendelian
23
Pathological and anatomical features distinguishing
ulcerative colitis from Crohn’s disease
Ulcerative colitis
Crohn’s disease
Distal
Segmental, proximal
Always
50% of cases
Normal thickness
Thickened
Rare
Common
Superficial layers
All layers
Superficial
Deep
Denuded
Cobblestones
Granulomas
0–4%
50–70%
Lymphocytic infiltration
Rare
Always
Fistulae
Rare
Common
Localisation
Rectum affected
Intestinal wall
Adhesions
Inflammation
Ulcerations
Mucous membrane
23
Pathological and anatomical features distinguishing
ulcerative colitis from Crohn’s disease
Macroscopy
UC
CD
Microscopy
UC
Excessive active ulcerative colitis changes with
cryptitis, cryptic abcesses and ulcers (H-E X200)
CD
Colonic granuloma in a patient with Crohn disease.
Hematoxylin-eosin staining. Courtesy of Dr E. Ruchelli.
22
Differences in clinical presentation between
ulcerative colitis and Crohn’s disease
Ulcerative colitis
Crohn’s disease
*
***
***
**
*
*
***
*
Blood
***
*
Mucus
*
**
Pus
*
**
Symptoms
Pain
General malaise
Fever
Diarrhoea
Stools
The number of * symbols indicates the frequency with which each
symptom is present
Clinical presentation of ulcerative
colitis
•
•
•
•
•
•
•
Bloody diarrhoea
Fever
Cramping abdominal pain
Weight loss
Frequency and urgency of defecation
Tenesmus
General malaise
12
Bloody diarrhea/Incontinence
• If inflammation is confined to the rectum,
blood is seen only on the surface of the stool.
• If inflammation is more extensive, blood is
mixed in with the stool.
• Although bloody diarrhea is considered the
dominant symptom in ulcerative colitis,
urgency and fecal incontinence bother more.
• Incontinence and the fear of incontinence are
the most limiting aspects of their disease
Physiscal findings
• Minimal
• tenderness over the affected area of the colon
• Rectal examination may reveal tenderness or blood on
the glove.
• In severe disease, the patient is more likely to be
febrile and tachycardic.
• Prolonged episodes of severe disease lead to muscle
wasting, edema and other signs of malnutrition.
• Chronic blood loss results in pallor.
• Children with severe disease may have retarded
growth and development
Initial attack
• may be fulminant, with bloody diarrhea present
from the beginning
• more commonly, the disease begins indolently,
with nonbloody diarrhea progressing to bloody
diarrhea
• symptoms often gradually worsen over the
course of a few weeks
• can present initially with any extent of anatomic
involvement, from disease confined to the
rectum to pancolitis and with any degree of
activity, from mild diarrhea to toxic megacolon
Initial attack
• colitis extending to the cecum is seen in only about 20% of
patients
• limited colitis is more common, with 75% of patients having
no disease proximal to the sigmoid
• extraintestinal manifestations, most commonly arthralgias
and mild arthritis, are present in fewer than 10% of
patients at initial presentation
• in mild ulcerative colitis, the rectal mucosa is
erythematous and edematous on endoscopic examination
• in more severe disease, edema is more marked, the
mucosa bleeds spontaneously and there is an extensive
purulent exudate
• in the most severe cases, frank ulceration is seen
Initial attack
• The outcome of the first attack of ulcerative
colitis can be predicted on the basis of the extent
of the disease and the severity of the symptoms.
• More than 90% of patients with mild disease go
into remission after the first attack.
• Among patients with more severe disease, a
significant number require colectomy and a few
worsen and die.
• Death occurs primarily in patients who present
with toxic megacolon
Clinical evaluation
• The frequency and severity of diarrhea is a
good first guide to the severity of the disease.
• Systemic signs and symptoms (fever,
hypotension, tachycardia) are markers for the
presence of severe disease and demand a
more extensive evaluation.
• Coexistence of irritable bowel syndrome with
ulcerative colitis makes evaluation of the
patient’s symptoms more difficult.
Table 6: Ulcerative colitis disease activity index.
1. Stool frequency
0-3: normal
1-3: 1-2 stools daily > normal
2-3: 3-4 stools
3-3: 4 stools
2. Rectal bleeding
0-3: None
1-3: Streaks of blood
2-3: Obvious blood
3-3: Mostly blood
3.Mucosal appearance
0-3: Normal
1-3: Mild friability
2-3: Moderate friability
3-3: Exudation, spontaneous bleeding
4. Physician's rating of disease activity
1-3: Normal
2-3: Mild
3-3: Moderate
4-3: Severe
Maximum score 3 13
Investigations
•
•
•
•
Endoscopy
Barium enema
Laboratory
Microbiological studies
Endoscopy-Colonoscopy
• is required at the initial presentation to help establish the
diagnosis and to define the extent of disease
• may be useful at presentation of subsequent attacks if there is any
question as to whether the attack is a recrudescence of ulcerative
colitis
• In patients with a past history of ulcerative colitis who develop
diarrhea, proctoscopy is a useful method for distinguishing
recurrences of ulcerative colitis from infectious diarrhea.
• may be indicated if a recurrence of ulcerative colitis is more severe
than earlier occurrences, suggesting anatomic extension of the
disease.
• surveillance for dysplasia
• response to drug therapy
Colonoscopy
• The characteristic findings of ulcerative colitis:
• rectal involvement with a confluent
distribution
• friable mucosa
• a blurred vascular pattern
• ulcerations in areas of active inflammation
Colonoscopy
3
Endoscopic features of ulcerative
colitis
(reproduced with permission, Schiller et al, 1986)
Figure 4.1a - Endoscopic features of active ulcerative
colitis
©Copyright Science Press Internet Services
Figure 4.1b - Endoscopic features of active ulcerative
colitis
©Copyright Science Press Internet Services
Figure 4.2 - Ulcerative colitis in remission
©Copyright Science Press Internet Services
Figure 4.3 - Severe ulcerative colitis
©Copyright Science Press Internet Services
Figure 4.4 - Severe ulcerative colitis with pseudopolyps
©Copyright Science Press Internet Services
Barium X-ray
• Plain films of the abdomen demonstrate
whether there is colonic dilation consistent
with toxic megacolon.
• Colonic dilation usually occurs without
obvious abdominal distention.
4
Radiological features of acute
ulcerative colitis
(from Wilson et al, 1991)
5
Radiological features of chronic
ulcerative colitis
(from Wilson et al, 1991)
6
Anatomical location of ulcerative colitis
Laboratory
• stools – culture
• blood: anemia, high sedimentation rate, low
Na, K, high creatinine, ureea, renal failure
Microbial agents
• Intercurrent intestinal infections, either bacterial
( Clostridium difficile, Campylobacter species,
Yersinia species) or viral (cytomegalovirus), have
been implicated in inducing exacerbations.
• Although one study reported high levels of
recovery of C. difficile toxin from patients with
symptomatic relapses, other studies have
reported low rates.
• Cytomegalovirus causes gastrointestinal infection
and is fairly common in the immunosuppressed
host (e.g., patients taking immunomodulators).
Natural history
• Most commonly, ulcerative colitis follows a chronic
intermittent course, marked by long periods of
quiescence interspersed with acute attacks lasting
weeks to months
• A small but significant percentage of patients suffer a
chronic, continuous course with persistent symptoms
and no complete remission
• The risk of relapse after the first attack of ulcerative
colitis is a function of the patient’s age at the time of
the first attack. Older patients are more likely than
younger ones to go long periods without relapse
Intestinal complications of ulcerative
colitis
•
•
•
•
•
•
Fibrosis
Shortening of the colon
Bleeding
Stricture
Bowel perforation
Toxic megacolon
7
Systemic complications of ulcerative
colitis
•
•
•
•
•
•
•
Arthritis
Iritis
Erythema nodosum
Pyoderma gangrenosum
Sclerosing cholangitis
Aphthous stomatitis
Thromboembolic disorders
8
9
Risk of cancer with ulcerative colitis
(reproduced with permission, the AGA Teaching Project, 1992)
10
Risk of colectomy with pancolitis
Disease duration
Risk of colectomy
Year of diagnosis
9%
Following 4 years
3% each year
Following years
1% per year
Relapse of ulcerative colitis during
pregnancy
15
Relapse in
pregnant
10
women with
UC, who were
remission at
5
conception
(%)
0
1st
2nd
(after Willoughby & Truelove, 1980) Trimester
3rd
Post-partum
11
Prognosis
• Those who present initially with proctitis have a more
benign course than those who present initially with
more extensive disease. These patients are likely to
respond to local therapy and thus are spared the side
effects of systemic therapy.
• Mortality in patients with ulcerative colitis has
decreased dramatically and now life expectancy is
similar to that of the general population.
• Ulcerative colitis has a significant lifelong impact on a
patient’s quality of life. Most patients lead productive
lives with 90% employed after treatment of the initial
attack
Crohn’s disease is a more complex and difficult clinical entity
than ulcerative colitis
- the diversity of anatomic locations in which it
is detected
- the effects of this diversity on presentation
- clinical course
- therapeutic options
Definition
• Crohn disease is an idiopathic, chronic,
transmural inflammatory process of the bowel
that often leads to fibrosis and obstructive
symptoms, which can affect any part of the
gastrointestinal (GI) tract from the mouth to the
anus.
• This condition is believed to be the result of an
imbalance between proinflammatory and antiinflammatory mediators.
• Most Crohn disease cases involve the small
bowel, particularly the terminal ileum.
Epidemiology
• The prevalence of Crohn disease is
approximately 7 cases per 100,000
population.
• The incidence and the prevalence of Crohn
disease (especially the colonic subset) seem to
have steadily increased over the last 5
decades, mainly in northern climates.
Registered number of patients and increased rates of patients with
Crohn's disease (CD) and ulcerative colitis (UC) over 30 years in Japan.
Epidemiology
Race
• Data on the racial incidence of Crohn disease seem to show that the
condition is uncommon in nonwhites in underdeveloped regions; however,
this is not applicable to nonwhites in urban settings, where the rate may
even exceed that of whites.1
• Crohn disease is seemingly more common in whites than in blacks or
Asians.1
Sex
• Most reports show a female-to-male ratio between unity and 1.2:1.
Age
• The age of onset of Crohn disease has a bimodal distribution. The first
peak occurs between the ages of 15 and 30 years, and the second peak
occurs between the ages of 60 and 80 years. However, most cases begin
before age 30 years. A greater proportion of colonic and distal Crohn
disease has been diagnosed in older patients, whereas younger patients
have predominantly ileal disease.
Etiology
• The exact cause of Crohn disease remains
unknown.
• Current theories implicate the role of genetic,
microbial, immunologic, environmental, dietary,
vascular, and even psychosocial factors as
potential causative agents.
• It has been suggested that patients have an
inherited susceptibility for an aberrant
immunologic response to one or more of these
provoking factors.
Etiology
• Environmental influences such as tobacco use seem to
have an effect on Crohn disease. Smoking has been
shown to double the risk, whereas in people who
smoke, the risk of developing ulcerative colitis is less
than in those who have never smoked.
• Infectious possibilities such as Mycobacterium
paratuberculosis, Pseudomonas species, and Listeria
species have all been implicated in the pathogenesis of
Crohn disease, suggesting that the inflammation seen
with the disease is the result of a dysfunctional but
appropriate response to an infectious source.
31
M. Paratuberculosis and Crohn’s
disease
Mycobacterium paratuberculosis has been
thought to have an aetiological role in Crohn’s
disease as:
• it causes a similar disease in the small
intestine in cattle (Johne’s disease)
• it can be found in milk
• it can be found in Crohn’s disease tissue,
although it is also found in other tissues
32
Measles virus and IBD
Measles virus has been associated with Crohn’s
disease due to:
• good epidemiological links between
perinatal measles infection and subsequent
Crohn’s disease
• a possible increase in the incidence of
Crohn’s disease in children of mothers who
had measles during pregnancy
• tissue studies suggest a higher than
expected proportion of patients with
Crohn’s disease
(Forbes, 1997)
There are three major patterns of
disease distribution
• disease present in the ileum and cecum, a
pattern seen in 40% of patients at presentation
• disease confined to the small intestine, a pattern
seen in 30% of patients at presentation
• disease confined to the colon, a pattern seen in
25% of patients at presentation
• Much less commonly, Crohn’s disease involves
more proximal parts of the gastrointestinal
tract—the mouth, the tongue, the esophagus,
the stomach and the duodenum.
Clinical presentation of Crohn’s
disease
•
•
•
•
•
•
•
•
Diarrhoea
Abdominal pain
Bleeding
Pyrexia
Weight loss
Fistulae
Perianal disease
General malaise
Any of these three symptoms may be most prominent, in contrast to ulcerative colitis, in
which diarrhea is almost universally the most prominent complaint
21
Initial presentation
• may not be dramatic
• Patients may complain for months or years of
vague abdominal pain and intermittent
diarrhea before the diagnosis of Crohn’s
disease is considered.
Initial presentation
• Can usually be characterized as either obstructing or
fistulizing.
• Obstructive disease is the result of inflammation narrowing
the intestinal lumen and obstructing the flow of intestinal
contents. Over time, fibrosis and thickening of the
intestinal wall also contribute to obstruction.
• Crampy abdominal pain, nausea, vomiting, and diarrhea
are the major symptoms associated with obstructing
disease.
• Fistulizing disease occurs when the inflammatory process
extends completely through the intestinal wall. The escape
of bacteria through these defects in the wall can result in
abscesses
Diarrhea
• The pattern varies with the anatomic location of the
disease
• In patients with colonic disease, especially with rectal
involvement, diarrhea may be of small volume and
associated with urgency and tenesmus.
• Prolonged rectal inflammation and scarring in the rectum
can leave it so rigid and nondistensible that the patient is
incontinent.
• In disease confined to the small intestine, stools are of
larger volume and are not associated with urgency or
tenesmus.
• Patients with severe involvement of the terminal ileum and
those who have had surgical resections of the terminal
ileum may have elements of bile salt diarrhea or, in more
severe cases, frank steatorrhea.
Diarrhea
• Strictures in the small intestine may lead to bacterial
overgrowth with deconjugation of bile salts and fat
malabsorption.
• If diarrhea is a product of fat malabsorption, the timing
and severity of the diarrhea are functions of the
pattern of fat ingestion.
• Internal fistulae are common in Crohn’s disease and
can lead to diarrhea either by colonization of the small
bowel with bacteria, as in enterocolonic fistulae, or
through bypass of large segments of absorptive
epithelium, as in enteroenteric or enterocolonic
fistulae.
Abdominal pain
• One common pain pattern is cramping right lower
quadrant pain in patients with ileocolonic disease.
• This pain usually occurs after eating and probably is
related to partial intermittent obstruction of a
narrowed intestinal lumen.
• Pain is caused by stretching of the wall in the dilated
segment proximal to the obstruction and by powerful
contractions of the small bowel musculature
attempting to push intestinal contents through the
obstructed segment.
• Abdominal distention, nausea, and vomiting may
accompany pain in this circumstance
Abdominal pain
• A second common pain pattern in Crohn’s disease
is visceral pain resulting from inflammation of the
serosa, as seen in transmural Crohn’s disease.
• The pathophysiologic basis of abdominal
• pain in nonobstructed or stable patients with
Crohn’s disease is less clear.
• Crohn’s disease is associated with an increased
risk of depression; pain management is more
difficult in patients with depression.
Weight loss
• Weight loss of some degree occurs in most patients
with Crohn’s disease, irrespective of anatomic location.
• Loss of more than 20% of body weight is less common,
occurring in 10% to 20% of affected persons.
• Some weight loss is a product of malabsorption, but
weight loss usually is a product of diminished intake.
• Patients, especially those with small bowel disease,
may avoid food because eating brings on pain or
diarrhea or, more commonly, because they are
anorectic.
Crohn’s disease may rarely involve the
stomach and duodenum
• Epigastric pain similar to that of duodenal
ulcer.
• Upper gastrointestinal series may show
ulceration and narrowing of the antrum and
duodenum.
• Aphthous ulcers and linear ulcers in the gastric
antrum may be seen on endoscopy.
Constitutional symptoms
• Fever and chills often accompany Crohn’s disease
activity
• A low-grade fever may be the patient’s first warning
sign of a flare of activity.
• Fatigue and malaise can reduce the ability to function
markedly and may impact work performance
negatively.
• Although they are more likely to complain of pain and
diarrhea, patients may be more bothered by fatigue. In
patients in whom fatigue is the dominant symptom,
coexisting depression should be considered.
EXTRAINTESTINAL MANIFESTATIONS
• two major groups:
• those in which the clinical activity follows the
activity of the bowel disease
• those in which the clinical activity is unrelated
to the clinical activity of the bowel disease.
• Most extraintestinal manifestations occur
more commonly with ulcerative colitis or
Crohn’s colitis than with Crohn’s disease
confined to the small intestine.
Extraintestinal manifestations
•
•
•
•
•
Peripheral arthritis
Axial arthritis
Osteoporosis
Renal complications
Dermatological manifestations (pyoderma
gangrenosum and erythema nodosum)
• Eye complications (uveitis and episcleritis)
• Thromboembolic complications (arterial as well as
venous events)
• Hepatobiliary complications (fatty liver,
pericholangitis, chronic active hepatitis and cirrhosis)
Physical findings
• When the disease is active, the patient looks pale,
weak, and chronically ill.
• Aphthous ulcers in the mouth are common in active
Crohn’s disease.
• The abdomen may be tender.
• Fistulous openings, induration, redness, or tenderness
near the anus suggest the presence of perianal Crohn’s
disease.
• The mucosa at the anal verge may appear purplish
because of vascular engorgement.
• Fissures in the anal canal can occur; bleeding from
these fissures can be confused with active colitis
Disease Activity Indices
Natural history
• Crohn’s disease, like ulcerative colitis, is a relapsing and remitting
disease.
• About 30% of placebo-treated patients with Crohn’s disease of mild
to moderate activity go into remission within 4 months.
• Conversely, in a group of patients with Crohn’s disease in remission
and not receiving any type of therapy, about 70% remained in
remission at 1 year and 50% at 2 years.
• Within 10 years of diagnosis, 60% of patients with Crohn’s disease
have surgery.
• Postoperatively, endoscopic signs of recurrence are seen in 70% of
patients at 1 year and recurrence of symptoms is seen in 40% to
50% within 4 years.
• Of those patients who have one surgical resection for Crohn’s
disease, 45% eventually require reoperation.
• The younger the age at onset, the more likely the patient will have
a complicated course and the more likely surgery will be required.
Investigations
•
•
•
•
•
•
Endoscopy
Barium X-ray
CT
MRI
Ultrasonography
Laboratory
Endoscopy
• to distinguish between ulcerative colitis and
Crohn’s disease
• to determine the extent and severity of disease
• to assess response to treatment
• to screen for dysplasia
• Due to its ability to visualize the mucosa directly
and obtain biopsies, endoscopy has become
established as the primary diagnostic tool.
Endoscopy
• rectal sparing
• areas of active disease interspersed with
normal mucosa
• sharp, punched-out ulcerations surrounded by
normal mucosa
• “cobblestoning,” or nodular mucosa often
intersected by crossing linear ulcerations.
Multiple linear ulcerations are seen on colonoscopy in this patient
with Crohn's disease.
Crohn's disease can mimic ulcerative colitis on endoscopy.
13
Endoscopic appearance of Crohn’s
disease
(reproduced with permission, Schiller et al, 1986)
Figure 4.15 - Severe Crohn`s colitis
©Copyright Science Press Internet Services
Figure 4.19 - Cutaneous opening of a perirectal fistula
©Copyright Science Press Internet Services
Figure 4.20 - Typical perianal changes of Crohn`s disease
©Copyright Science Press Internet Services
Radiology
• Contrast radiology and computed tomography (CT)
are both important in the management of Crohn’s
disease
• Air-contrast radiography is better for assessing mucosal
detail, colonic distensibility and the presence of
strictures.
• In an acutely ill patient with Crohn’s disease, a CT scan
is often the preferred initial diagnostic test to answer
urgent clinical questions concerning the presence of
abscesses or possible obstruction.
• Both techniques may be useful to detect the presence
of fistulae.
18-year-old woman with Crohn's disease involving colon. Image from double-contrast
barium enema obtained 2 days after A reveals longitudinal and perpendicular ulcerations
(arrows) in right colon.
36-year-old woman with Crohn's disease. CT enteroclysis image clearly shows small
fistula (arrow) between terminal ileum and adjacent ileal loop with severe
stranding of surrounding fat tissue.
Active Crohn disease and sampling
method used for attenuation
measurements in 55-year-old woman
with endoscopic and pathologic
diagnosis of active Crohn disease. (a)
Transverse CT scan shows mural
thickening and hyperenhancement
(arrows) relative to normal ileum
(arrowhead). Attenuation for diseased
ileum was 122 HU ± 12. Attenuation for
normal ileum was 55 HU ± 22. (b) Line
profile tool (white line) was placed
across the terminal ileal wall to
measure attenuation at 1-mm intervals.
Sampling is performed across entire
bowel wall (from mesenteric fat to
water-filled lumen) in the direction of
the arrow. (c) Histogram derived from b
shows attenuation measurements
across small-bowel wall, demonstrating
maximal attenuation (arrowhead),
perienteric fat (long arrow), and
contrast material–filled lumen (short
arrow).
CROHN’S DISEASE
-Radiology-
Radiological features of Crohn’s
disease
(reproduced with permission
from McGraw-Hill)
(courtesy of Dr Sten Norby
Rasmussen, Denmark)
14
15
Anatomical location of Crohn’s disease
Investigations
• Magnetic resonance imaging (MRI) can be superior to
CT scanning in demonstrating pelvic lesions. Because of
differential water content, MRI can differentiate active
inflammation from fibrosis, and it can distinguish
between inflammatory and (fixed) fibrostenotic lesions
in Crohn disease.
• Radionucleotide scanning may be helpful in assessing
the severity and extent of the disease in patients who
are too ill to undergo colonoscopy or barium studies
Ultrasound
• Ultrasonography is helpful in differentiating tubo-ovarian
pathology. However, this modality can also detect enlarged
lymph nodes, abscesses, stenoses, and even fistulae, and
ultrasonography is regarded as a quick and inexpensive
screening method to aid in the diagnosis of IBD or to
repeatedly evaluate patients for complications.
• Rectal endoscopic ultrasonography has been used as an
alternative to MRI in the assessment of perianal
disease. This technique allows the differentiation of simple
from complex fistulae, as well as the assessment of the
tracts of the fistulae in relation to the sphincter muscle.
Laboratory
•
•
•
•
•
•
•
•
Laboratory findings in Crohn’s disease are largely nonspecific.
Anemia resulting from chronic disease, blood loss
Nutritional deficiencies (iron, folate, or vitamin B 12)
A modestly elevated leukocyte count is indicative of active Crohn’s
disease, but a marked elevation suggests the presence of an
abscess or other suppurative complication.
Thrombocytosis may occur with active disease.
The erythrocyte sedimentation rate has been used to monitor
disease activity in Crohn’s disease, and it tends to be higher in
colonic disease than ileal disease.
Hypoalbuminemia is a good indication of disease severity and
malnutrition.
Ileal disease or resection of more than 100 cm of ileum results in a
diminished serum vitamin B 12 level because of malabsorption.
Differential diagnosis
• Crohn’s Disease and Ulcerative Colitis
• Inflammatory bowel disease VERSUS other
diseases
Intestinal complications of Crohn’s
disease
•
•
•
•
•
Fistulae
Abscesses
Adhesions
Strictures
Obstruction
16
17
Perianal complications of Crohn’s
disease
18
Risk of cancer with Crohn’s disease
and ulcerative colitis
(adapted from Hamilton, 1985, with permission)
Prognosis
• Although Crohn disease is a chronic condition with recurrent
relapses, appropriate medical and surgical therapy helps patients to
have a reasonable quality of life.
• Medical therapy becomes less effective with time and surgery for
underlying complications is required in nearly two thirds of patients
at some point in their disease.
• The mortality rate increases with the duration of the disease and
GI tract cancer is the leading cause of disease-related death,
including colorectal, small bowel adenocarcinoma, lymphomas, and
squamous cell carcinomas arising in association with a chronic
fistula to the skin. Some studies have also shown an association
between Crohn disease and respiratory cancers.
• Acute regional enteritis, which is often discovered during
laparotomy for suspected appendicitis, has an excellent prognosis.
The acute episode is treated conservatively, and two thirds of
patients may not have subsequent evidence of regional enteritis.
Intestinal Semiology
“As you could kill time
without injuring eternity”
Henry David Thoreau