| 2. Ulcerative
Colitis |
page
323 |
Ulcerative colitis is an
inflammatory disease of unknown etiology affecting the colonic mucosa from
the rectum to the cecum. It is a chronic disease characterized by rectal
bleeding and diarrhea, and given to remissions and exacerbations.
Ulcerative colitis is not a
distinct entity, since most of the histological features of the disease
may be seen in other inflammatory states of the colon, such as those
caused by bacteria or parasites. The diagnosis of ulcerative colitis,
therefore, rests on discovery of a combination of clinical and
pathological criteria, investigation of the extent and distribution of
lesions, and exclusion of other forms of inflammatory colitis caused by
infectious agents (Entamoeba histolytica, Clostridium difficile,
Campylobacter, E. coli and Shigella).
| 2.1 Pathophysiology |
page 323 |
Ulcerative colitis is an
inflammatory state confined to the mucosa, unlike Crohn’s disease,
which extends into deeper muscle layers of the serosa. Since the
inflammatory process involves only the mucosa, sharp localized abdominal
pain, perforation and fistula formation are uncommon in ulcerative
colitis; this is in contrast to Crohn’s disease, where they frequently
appear. Under light microscopy, the colonic tissue displays small
microabscesses, called crypt abscesses, which involve the crypts of
Lieberkühn. Polymorphonuclear cells accumulate in the crypt abscesses,
and frank necrosis of the surrounding crypt epithelium occurs; thus the
polymorphonuclear infiltrates extend into the colonic epithelium. These
microabscesses in the crypts are not visible to the naked eye; however,
several crypt abscesses may coalesce to produce a shallow ulceration
visible on the mucosal surface (Figure
3). Occasionally, lateral extension of crypt abscesses may
undermine the mucosa on three sides, and the resulting hanging fragment
of mucosa will appear endoscopically and radiographically as a “pseudopolyp.”
Following this mucosal destruction, highly vascular granulation tissue
develops in denuded areas, resulting in friability and bleeding. The two
most prominent symptoms of ulcerative colitis – diarrhea and rectal
bleeding – are related both to the extensive mucosal damage that
renders the colon less capable of absorbing electrolytes and water, and
to the highly friable vascular granulation tissue, which bleeds readily.
Radiographically, evident
foreshortening and narrowing of the colon, loss of haustral margins, and
apparent stricture formation will often be seen. These findings,
however, are often reversible, since they are due to hypertrophy and
spasm of the muscularis mucosa and not to fibrosis.
| 2.2 Clinical Features |
page
324 |
Ulcerative colitis
typically occurs in patients between 20 and 50 years of age and may
present as an early acute fulminating attack or may follow a rather
indolent and often chronic course. Approximately 70% of patients will
have complete symptomatic remissions between intermittent attacks. Ten
percent of patients will have one initial attack and will experience
no subsequent attacks, and 15–20% will be troubled by continuous
symptoms that occur without remission.
The initial and most
common symptom of ulcerative colitis is rectal bleeding. A blood stain
on the toilet tissue or the appearance of bloody mucus on the surface
of stools is usually the first symptom noticed. This initial bleeding
is often mistaken for bleeding from hemorrhoids. Indeed, this first
evidence of blood may follow a bout of constipation, which can
sometimes be the presenting complaint. When constipation is the
presenting complaint, the colitis is most often associated with
disease limited to the rectum, where spasm prevents feces from
entering the area involved. Hence, initial constipation or normal
bowel habits may be the hallmark of ulcerative proctosigmoiditis.
Diarrhea occurs with
more extensive colonic involvement, and blood is usually mixed with
the feces. The principal mechanism responsible for diarrhea in
ulcerative colitis is exudation with resultant secretion of
interstitial fluids and loss of mucosal surface area for absorbing
fluid and electrolytes and water. In addition, involvement of the
rectum prevents this segment of the colon from acting as a reservoir
for fecal contents prior to defecation. This rectal irritability
causes frequent bowel evacuation of minute amounts of blood and mucus,
an activity that can be termed “pseudodiarrhea.”
Since the severity of
the disease will affect the therapeutic approach and, indeed, the
prognostic implications, it is important for the physician to assess
the severity of the disease for every patient. The best indices of
severity are clinical signs and symptoms. Large volumes of diarrhea
indicate that the colonic mucosa has been involved to the extent that
sodium and water absorption are significantly impaired. Frequency,
however, is an unreliable indicator of severity because frequent bowel
movements can indicate either large-volume diarrhea or rectal
irritability. Large quantities of blood in the stools, a fallen
hemoglobin concentration, and hypoalbuminemia as a consequence of loss
of albumin into the stool are signs of widespread disease. Elevated
erythrocyte sedimentation rate, fever, and abdominal pain and
tenderness may point to transmural extension of the disease and the
development of severe ulcerative colitis.
Ulcerative colitis can
be classified according to grade of clinical severity:
1. Severe. Diarrhea comprising six or more movements per day,
macroscopic blood in the stools, fever, tachycardia greater than
90/min, anemia and an elevated erythrocyte sedimentation rate.
2. Moderate. Diarrhea comprising four or fewer movements per
day, small amounts of macroscopic blood in stools, no fever, no
tachycardia, mild anemia and a minimally elevated erythrocyte
sedimentation rate.
3. Mild. Diarrhea comprising fewer than four bowel movements
per day without anemia, fever, tachycardia, weight loss or
hypoalbuminemia.
| 2.2.1 SEVERE ULCERATIVE COLITIS |
|
Severe ulcerative
colitis, the least common form of the disease, occurs in 15% of all
patients with ulcerative colitis. This form of the disease may be the
initial presentation or may represent a progression from a less severe
attack. Diarrhea is profuse and rectal bleeding is constant and
severe. Fever is marked and sustained, and appetite and weight are
both severely diminished. Abdominal cramps are severe and tenderness
may be localized, indicating impending perforation. Leukocytes greater
than 10,000, severe anemia, and hypoalbuminemia resulting from low
protein intake (anorexia) and increased chronic loss of albumin are
hallmarks of this form of the disease.
Medical therapy is
often ineffective for this type of patient, and colectomy is often
required.
| 2.2.2 MODERATE ULCERATIVE
COLITIS |
|
Moderate ulcerative
colitis affects 25% of all patients with ulcerative colitis. Diarrhea
is the major symptom, and it occurs three to four times per day.
Invariably, the diarrhea contains macroscopic amounts of blood.
Abdominal pain may occur and may awaken the patient at night; usually
the cramps are relieved by defecation. Low-grade fever may exist, and
the patient may complain of fatigue, anorexia and some mild weight
loss.
Generally, moderate
ulcerative colitis responds quickly to appropriate therapy. Immediate
mortality in this group is low. However, the long-term prognosis is
for repeated attacks of equal or greater severity, and the risk of
ultimately developing cancer in the affected colon is appreciable. As
well, at any time during the moderate attack of ulcerative colitis,
the patient may become severely ill, developing a severe fulminant
colitis characterized by high fever, profuse diarrhea, progressive
dilation of the colon (toxic megacolon) and rapid deterioration.
| 2.2.3 MILD ULCERATIVE COLITIS |
|
Mild ulcerative colitis
is the most common form of the disease, occurring in 60% of patients.
In 80% of those affected with mild disease, the ulcerative colitis
will be limited to the distal colon (sigmoid and rectum); in the other
20% the whole colon will be involved. The age, sex and familial
incidence of ulcerative colitis are the same for mild disease as for
severe disease. As well, the number of patients who have only one
attack, intermittent attacks, or continuous disease is the same for
both mild and severe ulcerative colitis.
In the case of mild
disease limited to the rectal sigmoid, most often the disease will
remain in this area; however, in 10% of these patients it will
eventually involve the entire colon and bring about the simultaneous
development of severe diarrhea and bleeding.
Neither colonic
bleeding nor diarrhea is severe in mild ulcerative colitis, and the
systemic complications of anorexia, weight loss and fatigue are not
seen. Occasionally, the patient may suffer from a few days of crampy
lower abdominal pain; however, hospitalization is usually not required
and mild ulcerative colitis responds rapidly to therapy.
For patients who have
mild ulcerative colitis, particularly proctosigmoiditis, the rate of
colonic cancer is similar to that of control populations. Thus,
colonic cancer occurs in mild cases of ulcerative colitis only
one-fifth as often as in the more severe forms of the disease.
The diagnosis of
ulcerative colitis is made on the basis of the clinical symptoms
listed above, on physical findings, and on the results of laboratory
and endoscopic investigations.
| 2.3.1 PHYSICAL EXAMINATION |
|
Physical examination
during mild ulcerative colitis or between attacks may yield completely
normal findings. In contrast to Crohn’s disease, there are no
palpable masses and no specific areas of tenderness, unless serosal
involvement, peritoneal irritation or impending perforation (toxic
megacolon) exists. Occasionally, the liver is palpable because of
fatty infiltration or other hepatic abnormality. Auscultation of the
abdomen may reveal increased bowel sounds and audible borborygmi. With
toxic megacolon, bowel sounds are quiet or absent.
Rectal examination is usually painful and the anal
sphincter is often spastic. The examiner may be able to detect gritty,
coarse, granular changes in the rectal mucosa on digital palpation.
Pseudopolyps may also be palpated, and a rectal stricture may be
detected. In addition, it may be possible to feel a carcinoma. Rectal
and perianal complications are far less frequent and destructive than
in Crohn’s disease and ordinarily consist only of minor fissures.
Examination of the skin and joints may confirm
extracolonic complications (uveitis, stomatitis, pyoderma gangrenosum,
erythema nodosum, large-joint arthritis, ankylosing spondylitis).
| 2.3.2 LABORATORY INVESTIGATIONS |
|
There is no single
laboratory test that will confirm ulcerative colitis. Anemia,
leukocytosis and an elevated erythrocyte sedimentation rate often
reflect the severity of the disease. Iron studies reflect iron
deficiency anemia (low serum iron, high TIBC, low ferritin).
Electrolyte abnormalities including hypokalemia, metabolic acidosis,
hypocalcemia, hypomagnesemia and/or hypoalbuminemia may exist in
patients with severe diarrhea. Liver function studies will demonstrate
an elevated alkaline phosphatase as a manifestation of sclerosing
cholangitis. Blood cultures may be positive in patients with toxic
megacolon.
Examination of the stool will reveal abundant red
and white blood cells. Stool cultures for Shigella, Campylobacter,
Salmonella, Clostridium difficile (culture and toxin), E. coli 0157
and Entamoeba histolytica should be done in all cases to exclude the
possibility of infectious colitis.
| 2.3.3 ENDOSCOPIC FINDINGS |
|
The most useful method
of establishing a diagnosis of ulcerative colitis is to assess the
integrity of the mucosa directly. Since 97% of people with ulcerative
colitis have involvement of the rectum, simple sigmoidoscopy can be
used to establish the diagnosis in the majority of cases.
The normal colonic mucosa is a smooth, glistening,
pink surface. Seen underneath this smooth surface are the ramifying
superficial submucosal blood vessels, which present a prominent
vascular pattern. When brushed by a cotton swab, the normal colonic
mucosa does not bleed because the mucosa is not friable.
Endoscopic examination of inactive or quiescent
ulcerative colitis shows a distorted or absent mucosal vascular
pattern with a mild granularity (Table
8). Mildly active disease shows continuous or focal erythema
and friability. Moderately active disease displays mucopurulent
exudate (mucopus) and ulcers less than 5 mm in diameter and fewer than
10 per 10 cm segment. Severe colitis demonstrates ulcers larger than 5
mm and more than 10 per 10 cm segment; these ulcers are often
accompanied by spontaneous bleeding.
TABLE
8. Endoscopic grading of activity in ulcerative colitis
|
| Activity |
Appearance |
|
| Quiescent |
Distorted
or absent mucosal vascular pattern
Granularity |
| Mildly
active |
Continuous
or focal erythema
Friability (touch bleeding) |
| Moderately
active |
Mucopurulent
exudate (mucopus)
Single or multiple ulcers (<5 mm); fewer than 10 per 10 cm
segment |
| Severe |
Large
ulcers (>5 mm); more than 10 per 10 cm segment
Spontaneous bleeding |
|
Colonoscopy is rarely necessary in diagnosing a
new case of ulcerative colitis. The rectal and distal sigmoid mucosa
is almost always involved in cases of ulcerative colitis, and a
carefully performed sigmoidoscopy with either a rigid or flexible
instrument can usually lead to the correct diagnosis. Colonoscopy
should never be performed in the case of acute, moderately severe or
severe ulcerative colitis because of the risk of perforation during
the procedure itself.
Colonoscopy for ulcerative colitis is, therefore,
performed for specific indications only. These are (1) to determine
the extent and/or activity of the disease in patients who are
considered to be in poor symptomatic control; (2) to perform cancer
surveillance or diagnosis; and (3) to determine the type of
inflammatory disease, whether ulcerative colitis or Crohn’s
disease (Table
9).
TABLE 9.
Inflammatory bowel disease: indications for colonoscopy
|
Differentiating IBD
from other diseases and differentiating Crohn's from
ulcerative colitis
Establishing the extent of the disease
Screening for malignancy and malignant precursors
Evaluation of abnormalities on radiographs
Evaluation of patients not responsive to standard therapy or
examination to explain recent flare; searching for
complications
Examination prior to surgery
- Detection of intestinal involvement (active IBD) in
fistulous disease
- Differentiation of ulcerative colitis from Crohn's
colitis
|
|
| 2.3.4 RADIOLOGIC FINDINGS |
|
A plain film of the
abdomen should always be obtained, particularly with severe colitis,
where the risk of toxic megacolon exists. The plain film may
demonstrate foreshortening or loss of haustration; sufficient air in
a segment of colon to silhouette the mucosa may reveal irregular
mucosa, ulceration and mucosal tags. Patients with toxic megacolon
will have mid-transverse colon dilation to a diameter of 6 cm or
more.
An air contrast barium enema examination can be
used for the same indications as for colonoscopy: to determine
disease extent and/or activity, examine for cancer, or differentiate
from Crohn’s disease. Barium enema examination should thus be
performed on all patients with ulcerative colitis, but only at an
appropriate time. During the active disease phase, the colonic
preparation, and even the barium enema itself, may precipitate a
toxic megacolon. It is therefore prudent to delay the barium enema
examination until the disease has been brought under medical
control.
Radiologic features vary according to the
location and state of the disease. There may be a loss of
haustration on the left side of the colon (this can be the normal
appearance of the colon in elderly patients) (Figure
4). Additionally, the radiolucent filling defects of
pseudopolyps may be seen scattered throughout the colon.
Despite significant advances in radiography,
comparisons of results from colonoscopy and double contrast barium
enema suggest that the extent of the disease is often considerably
underestimated with the barium enema. Nevertheless, colonoscopy is
best reserved for investigating the disease of patients who have
considerable symptoms of colitis yet have minimal changes on
sigmoidoscopy and in barium enema results, and for obtaining
biopsies of suspicious areas.
| 2.4 Differential
Diagnosis |
page
330 |
The disorder from
which ulcerative colitis needs to be distinguished is Crohn’s
disease of the colon. In addition, a host of other diseases may
resemble ulcerative colitis. The possibility of these diseases must
also be excluded (Table
10).
TABLE
10. Differential diagnosis of ulcerative colitis
|
Infectious
Viral
Cytomegalovirus
Herpes
Bacterial
Salmonella species
Shigella species
Yersinia enterocolitica
Vibrio parahaemolyticus
Aeromonas hydrophila
Neisseria gonorrhoeae
Chlamydia trachomatis
Syphilis
Staphylococcus aureus
Escherichia coli
Protozoan
Amebiasis
Balantidiasis
Schistosomiasis
Fungal
Histoplasmosis
Candidiasis
Other
Clostridium difficile
Radiation
colitis
Crohn's
colitis
Medication/drugs
Enemas
Laxatives
Local nonsteroidal anti-inflammatory drugs
Sulfasalazine
Penicillamine
Gold
Methyldopa
Eosinophilic
gastroenteritis
Behçet's
syndrome
Colitis in
graft-versus-host disease |
|
Methods of
distinguishing between ulcerative colitis and Crohn’s colitis are
illustrated in (Table
11). It is important to note that, because of the anatomic
distribution of ulcerative colitis, proctosigmoidoscopic examination
is abnormal in virtually all cases. By contrast, even when Crohn’s
disease affects the colon, it often does not involve the rectum. In
addition, perianal disease is much more characteristic of Crohn’s
disease. Although diarrhea and weight loss occur with approximately
equal frequency in both diseases, abdominal pain is more evident
with Crohn’s disease. Extraintestinal manifestations occur in
about the same proportion with both diseases.
TABLE
11. Clinical differentiation of ulcerative colitis from
Crohn's colitis
|
| Feature |
Ulcerative
colitis |
Crohn's
colitis |
|
| Clinical
features |
|
|
| Rectal
bleeding |
Very
common - 90% |
Uncommon:
may be occult |
| Diarrhea |
Early,
frequent, small stools |
Less
prevalent or absent |
| Abdominal
pain |
Predefecatory,
urgency |
Colicky,
postprandial |
| Fever |
Uncommon
if uncomplicated |
Frequent |
| Palpable
mass |
Rare |
Frequent,
right lower quadrant |
| Recurrence
after resection |
Rare |
Frequent |
| Clinical
course |
Relapses/remissions
65%
Chronic/continuous 20-30%
Acute/fulminating 5-8% |
Usually
slowly progressive; fulminant |
| Endoscopic
features |
|
|
| Proctosigmoidoscopy |
Diffuse
pinpoint ulcerations,continuous lesions |
Discrete
aphthoid ulcerations,patchy lesions |
| Radiologic
features |
|
|
| Rectal
involvement |
Invariable |
Infrequent |
| Distribution |
Continuous |
Segmental,
discontinuous |
| Mucosa |
Fine
ulcerations |
"Cobblestones" |
| Strictures |
Rare |
Frequent |
| Fistulas |
Rare |
Frequent |
| Histologic
features |
|
|
| Distribution |
Mucosal |
Transmural |
| Cellular
infiltrate |
Polymorphs |
Lymphocytes |
| Glands |
Mucin
depletion
- Gland destruction
- Crypt abscesses
|
Gland
preservation |
| Special
features |
None |
Granulomas,
aphthoid ulcers, histiocyte-lined fissures |
|
CONTINUE
to See Part 2 of this subsection |