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Ulcerative colitis: Diagnosis and management

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 Outcomes -Based Practice

Series Editor: Bryan A. Liang, MD, PhD, JD

Ulcerative Colitis:
Diagnosis and Management
Case Study and Commentary: Paul T. Kefalides, MD, and Stephen B. Hanauer, MD, MC

DR. LIANG: mation of the colonic and rectal mucosal lining. How-
Ulcerative colitis, also known as chronic ulceration of ever, it is currently not known whether the disease has a
the intestines, is a common disorder estimated to have genetic and/or autoimmune etiology or is related to a
an incidence of 1 in 1000 persons in western coun- broad array of contributing factors, such as diet and
tries.1 Effective treatment relies on accurate and timely infection.12 Because of the symptomatic effect the dis-
diagnosis. Various factors contribute to the disease’s ease has on children, they often will also have poor oral
clinical manifestations, including psychiatric and physi- intake and concomitant malnutrition. Growth delays,
cal components, but the etiology of the disease re- poor development, and delayed sexual maturity can
mains poorly understood.2 – 4 result and contribute to a high risk for depression in
In patients with bloody diarrhea, such as the patient these patients.13
in this case study, there are many differential diagnoses Of particular concern in children with severe dis-
to consider. Diagnoses to be excluded at the outset of ease is whether or not it is appropriate to use cortico-
illness, based on patients’ risk factors, include radiation steroids. Besides possible adverse effects (eg, Cushing’s
injury, diversion colitis, and ischemia. The presence of syndrome, metabolic abnormalities, adrenal suppres-
pancolitis should increase a physician’s suspicion of sion, osteoporosis, cataracts), use of corticosteroids
disorders with potential infectious etiologies, such as places children at high risk for growth and develop-
amebic colitis, which is similar in presentation to ulcer- mental delays and greater severity of varicella infec-
ative colitis.5,6 Additionally, it is often difficult to distin- tions, if and when they occur.14 Thus, the primary care
guish between ulcerative colitis and Crohn’s disease in physician must be fully aware of the potential negative
patients with pancolitis; roughly 10% of affected effects of treatment when managing the case of a pedi-
patients will have only an indeterminate diagnosis of atric patient.
colitis until further work-up determines the specific Overall, a timely and accurate diagnosis is essential
type.7 – 9 to benefit patients with ulcerative colitis, because effec-
Bloody diarrhea, an important presenting symp- tive treatments for the disease exist. A risk-benefit
tom, is generally (but not always) characteristic of assessment must be carefully made prior to initiating
ulcerative colitis, whereas Crohn’s disease usually pre- any therapy, however, in light of the potentially signifi-
sents as nonbloody diarrhea. Moreover, ulcerative coli- cant adverse effects of some treatments, particularly in a
tis often begins in the rectum and spreads proximally pediatric population. With appropriate diagnosis, edu-
and continuously, whereas Crohn’s disease often skips cation, treatment, and patient compliance, ulcerative
some areas of the bowel and spares the rectum in as
many as 50% of cases.10 These findings are apparent
on endoscopic examination—a necessary component Dr. Kefalides is affiliated with the University of California at San Diego,
of any investigation of colitis. San Diego, CA. Dr. Hanauer is a Professor of Medicine and Clinical
Pharmacology and Director, Section of Gastroenterology and Nutrition,
An area of increasing concern is pediatric ulcerative
University of Chicago, Chicago, IL. Dr. Liang is the Arthur W. Grayson
colitis, which has an incidence of 2 to 4 per 100,000 chil- Distinguished Professor of Law & Medicine, Southern Illinois
dren; median age at diagnosis is 10 years.11 In general, University School of Law and School of Medicine, Carbondale, IL; and
pediatric ulcerative colitis presents as a chronic inflam- a member of the Hospital Physician Editorial Board.

www.turner-white.com Hospital Physician June 2002 53

 Kefalides et al : Ulcerative Colitis : pp. 53 – 63

colitis can be successfully addressed, and patients can blood and abdominal cramping over the past 4 days.
successfully participate in their activities of daily living. She reports no fever or chills. Her appetite has been
poor for the past 3 days. She has no history of recent
travel and has been eating at home.
DRS. KEFALIDES AND HANAUER:
Ulcerative colitis is a chronic inflammatory bowel dis- • What information should be sought when a patient
ease of the colon that has become increasingly common presents with diarrhea?
in first-world countries. Ulcerative colitis and Crohn’s dis-
ease comprise the spectrum of inflammatory bowel dis- For any patient presenting with chronic diarrhea, the
ease. These diseases affect approximately 400,000 individ- primary care physician must try to distinguish between
uals in the United States, and their economic impact has pathologic causes and irritable bowel syndrome.
been estimated at $2 billion annually.15 Irritable bowel syndrome is the most common cause of
Ulcerative colitis and Crohn’s disease share many loose bowel movements associated with abdominal
epidemiologic features. They can affect persons of any cramping; in this condition, loose bowel movements
age group, although they typically begin in the second often alternate with constipation. In contrast to inflam-
or third decade of life. They are most common in matory bowel disease, irritable bowel syndrome is not
developed countries and can occur in persons, or associated with blood in the stool, nocturnal bowel
more commonly their descendants, who have moved movements, weight loss, or other inflammatory sequelae
from second- or third-world countries to more indus- (eg, fever, arthritis, skin or eye lesions, perianal disease).
trialized environments. These disorders have a genetic The presence of blood or pus (fecal leukocytes) is associ-
component and occur more often in families in which ated with inflammation or neoplasia; in contrast, mucus
another individual has the diagnosis. Approximately is a normal constituent of stool, and neither its presence
10% to 30% of patients with inflammatory bowel dis- nor its absence has any specificity for either condition.
ease report having a family member with inflammatory In addition, specific risk factors for diarrheal illness
bowel disease.16 Certain environmental factors, particu- should be sought, such as recent antibiotic use (with its
larly cigarette smoking, affect the development and risk for Clostridium difficile infection), other contacts who
course of these diseases. have acute or chronic diarrhea, or recent travel.
In order to diagnose inflammatory bowel disease and
to distinguish ulcerative colitis from other diarrheal dis- Further History
orders, the physician must review the patient’s history On further questioning, the patient reports that her
and integrate historical information with physical exami- bowel movements are sometimes dark and watery. She
nation, laboratory, endoscopic, and pathologic findings. reports moving her bowels about 5 times per day and
Inflammatory bowel disease in general, and ulcerative about 2 to 3 times during the night. She has seen blood
colitis specifically, are lifelong disorders that greatly influ- mixed with the stool but believes the blood is coming
ence overall health, health care utilization, and quality of from a hemorrhoid, although she has never noted anal
life. Several studies have shown, however, that life skin tags. Her only medications are vitamins and occa-
expectancy in patients with ulcerative colitis is normal, sional ibuprofen for menstrual cramps. She has no aller-
especially in those with mild or limited disease.17 There- gies and no history of hospitalization or surgery. Family
fore, the goals of management of this chronic inflamma- history is notable for spastic colon in her mother and
tory disease are to induce and then maintain clinical colitis in her father’s brother. The patient has 2 siblings,
remission while minimizing the risk for complications both of whom are well. She is a graduate student in the
related to the disease or the medications used to treat it. humanities and works part-time in an office. She was a
Currently, ulcerative colitis can be cured only by surgery. smoker while in high school and undergraduate college
but quit approximately 6 months ago. She typically has
CASE STUDY 1 to 3 alcoholic drinks on the weekends but reports no
Initial Presentation and History drug use or HIV risk factors.
A 23-year-old woman with a history of dysmenor-
rhea associated with abdominal cramping goes to her • What additional risk factors for inflammatory bowel
primary care physician because of a 1-year history of disease are present in this history?
episodic diarrhea and blood-streaked stools; symptoms
have become more bothersome over the past 4 weeks. The patient’s report of blood in the stool or at the
She reports loose stools with increasing amounts of time of bowel movements is highly suggestive of

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 Kefalides et al : Ulcerative Colitis : pp. 53 – 63

inflammatory diarrhea with loss of mucosal integrity. will have decreased or absent bowel sounds, distension,
The diarrhea may be infectious or may represent and tympany. The latter are ominous changes that can
inflammatory bowel disease. Nocturnal bowel move- reflect the development of toxic megacolon, a dilation
ments are almost never seen in irritable bowel syn- of the colon with thinning of the colonic wall that can
drome but are common in inflammatory bowel disease. lead to perforation.
Recent cessation of smoking is a known risk factor for
development of ulcerative colitis. For an as yet un- Laboratory Examination
known reason, cigarette smoking protects against the The physician orders a comprehensive metabolic
development of ulcerative colitis but is associated with profile, complete blood count with differential, and
the development of Crohn’s disease.18 Nonsteroidal erythrocyte sedimentation rate (ESR). Stool samples
anti-inflammatory drugs (NSAIDs) such as ibuprofen are sent for testing for microbial pathogens. The
disrupt gastrointestinal mucosal integrity and may pre- results of laboratory testing are shown in Table 1.
cipitate or cause a flare of inflammatory bowel disease. Testing of stool for ova and parasites and culture for
Because there is a genetic predisposition for inflamma- C. difficile toxin have negative results. A test for fecal
tory bowel disease, a family history of colitis may reflect leukocytes is positive.
either irritable bowel syndrome or inflammatory bowel
disease, depending on the validity of the described fam- • How do these laboratory findings help focus the
ily history. All these factors should heighten the suspi- differential diagnosis?
cion of inflammatory bowel disease as the cause of this
patient’s symptoms. The presence of fecal leukocytes is diagnostic for
inflammatory diarrhea, whereas the negative cultures
Physical Examination and absence of C. difficile toxin, along with the long
On physical examination, the patient is slim and duration of symptoms, exclude many acute infectious
slightly pale. Her temperature is 37.8°C (100°F), heart causes of diarrhea. The anemia and thrombocytosis
rate is 90 bpm, and blood pressure is 110/60 mm Hg. are indicative of a chronic process with a high likeli-
Her oral mucosa is dry. There is no adenopathy in the hood of inflammation and/or iron deficiency. The
cervical chain. She has a midsystolic click on cardiac electrolyte values confirm the physical examination
examination and clear lungs. Her abdomen is flat, with findings of volume depletion, and the hypokalemia is
normal bowel sounds. There is mild tenderness dif- consistent with the history of chronic diarrhea. The
fusely but no rebound tenderness or guarding. The hypoalbuminemia may reflect loss of protein from
rectal examination shows no external lesions and no damaged colonic mucosa or may be a consequence of
stool is obtainable, but the mucus on the glove is posi- malnutrition in the setting of systemic inflammation.
tive for occult blood. The patient’s skin appears nor-
mal. Musculoskeletal examination shows no joint • What are the indications for endoscopy in a patient
swelling or tenderness. presenting with diarrhea?

• What physical findings are important in a patient Flexible sigmoidoscopy or colonoscopy is indicated
with ulcerative colitis? for evaluation of diarrhea when diarrhea is persistent,
when noninvasive tests do not reveal a pathogen, or
Results of physical examination in patients with when inflammatory symptoms or signs are present. A
ulcerative colitis may be normal or may represent subtle recent study showed that for patients with diarrhea,
changes caused by the presence of colitis. The subtle examination and biopsy of the distal colon is 99% sensi-
findings to note in a patient with suspected inflammato- tive for colonic pathology.19 Endoscopic examination
ry bowel disease include pallor (anemia), ocular inflam- can provide supportive evidence of colonic inflamma-
mation (episcleritis or iritis), oral ulcers, skin lesions tion, allow for tissue or stool sampling, and evaluate the
(erythema nodosum, pyoderma gangrenosum), peri- extent and severity of disease. Severity in ulcerative coli-
anal skin tags or fistulae (associated with Crohn’s dis- tis can be judged by the extent and degree of the
ease), or large-joint arthritis. In cases of severe ulcera- colonic injury as seen on endoscopy. In mild cases of
tive colitis, weight loss, fever, and tachycardia may be ulcerative colitis, only a small area of the distal colon is
seen. Results of abdominal examination may show gen- involved; in severe cases, there can be pancolitis. The
eralized tenderness in the setting of active disease or inflammatory injury in the colon progresses from a loss
may be normal. In cases of severe colitis, the abdomen of vascular pattern with granularity and friability in mild

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 Kefalides et al : Ulcerative Colitis : pp. 53 – 63

Table 1. Laboratory Test Results in the Case Patient matory cells in the lamina propria from the macro-
scopically involved areas. The biopsy samples taken from
Serum values normal-appearing mucosa are entirely normal.
Sodium 39 mEq/L
Potassium 3.4 mEq/L • What are the pathologic features of ulcerative colitis?
Chloride 101 mEq/L
Pathology
Bicarbonate 21 mEq/L
Histologic examination for ulcerative colitis in a pa-
Creatinine 0.7 mg/dL
tient with acute symptoms usually shows an inflammatory
Albumin 3.2 g/dL infiltrate consistent with acute colitis with polymor-
Total protein 6.7 g/dL phonuclear cells and background findings of chronic
Alkaline phosphatase 110 U/L inflammation. These features of chronic inflammation—
Total bilirubin 0.7 mg/dL cryptitis and crypt abscesses—indicate the presence of
Aspartate aminotransferase 45 U/L
concomitant chronic inflammation and help distinguish
(AST, SGOT) inflammatory bowel disease from acute self-limited coli-
tis (a sudden inflammatory injury to the colon that spon-
Blood urea nitrogen 30 mg/dL
taneously remits, such as infectious colitis, ischemic coli-
Hematologic values tis, and NSAID colitis). None of these features is specific
Leukocyte count 10.9 × 103/mm3 for ulcerative colitis—they can be present in infectious
Hemoglobin 11.3 g/dL colitis or other inflammatory conditions, such as Crohn’s
Hematocrit 33.2%
disease.20 A pathologist’s experience with inflammatory
bowel disease will determine how easily he or she can dif-
Platelet count 368 × 103/mm3
ferentiate it from acute self-limited colitis. The condi-
Erythrocyte sedimentation rate 73 mm/hr tions most commonly confused with inflammatory bowel
disease are Campylobacter and Yersinia infections, amebic
infections of the colon, and ischemic colitis.21 The differ-
cases, to superficial ulceration in patients with moderate ential diagnosis of ulcerative colitis is shown in Table 2.
severity, and then to deep ulceration with overlying Distinguishing ulcerative colitis from Crohn’s dis-
mucopus in extremely severe cases. Clinically, there may ease is also essential, because treatments and anticipat-
be markers for severe inflammation. Generally, patients ed complications will differ. Because it is sometimes not
with a more rapid onset of symptoms and more impres- possible to make this distinction early in the course of
sive signs of systemic inflammation are noted to have disease, some patients are given a diagnosis of “indeter-
more severe colitis at endoscopy. minate colitis.” As the disease develops, it will likely
Although flexible sigmoidoscopy is an efficient way to begin to fit a pattern that is more consistent with either
evaluate a patient with diarrhea, if the sigmoidoscopy ulcerative colitis or Crohn’s disease. Differentiating
leads to a diagnosis of inflammatory bowel disease, a full infectious colitis from inflammatory bowel disease or
colonoscopy is indicated to examine the entire colon for ischemic colitis by endoscopy alone may not be possi-
discontinuous areas of inflammation (known as skip ble, although the endoscopic impression may be con-
lesions) and to visualize the terminal ileum. sistent with the clinical diagnosis. Affected mucosa in
ulcerative colitis can regenerate and heal to a virtually
Endoscopic Evaluation and Biopsy normal appearance; therefore, for longstanding cases,
The physician performs a flexible sigmoidoscopy biopsies are useful to identify histologic changes of
examination that reveals a diffuse pattern of erythema, chronic inflammatory bowel disease (crypt architectur-
superficial ulceration, friability, and mucopus extend- al distortion) or other forms of “microscopic colitis”
ing in a continuous pattern from the anal verge to the (eg, collagenous colitis). Biopsy of normal and abnor-
splenic flexure. A demarcation is noted 55 cm from the mal mucosa is required to reveal quiescent colitis and
anal verge. The mucosa proximal to this point appears to determine if skip lesions are present. Skip lesions
normal. Biopsies are taken from both the affected and are seen in Crohn’s disease, but the inflammation of
normal-appearing areas. ulcerative colitis is usually in a continuous pattern.21
Pathologic examination of the biopsy samples reveals Histology can also help predict the future severity of
diffuse, continuous crypt architectural distortion with a patient’s ulcerative colitis course. A recent study that
crypt abscesses and expanded acute and chronic inflam- evaluated clinical factors that predict frequent relapses

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 Kefalides et al : Ulcerative Colitis : pp. 53 – 63

Table 2. Differential Diagnosis of Ulcerative Colitis

Disease Clinical Characteristics Histologic Characteristics

Ulcerative colitis Bloody diarrhea Distortion of crypts; acute and chronic diffuse
inflammatory infiltrate; goblet cell depletion;
crypt abscesses; lymphoid aggregates
Crohn’s colitis Perianal lesions common; frank bleeding Focal inflammation; submucosal involvement;
less frequent than in ulcerative colitis granulomas; goblet cell preservation; trans-
mural inflammation; fissuring
Ischemic colitis Older age groups; vascular disease; sudden Mucosal necrosis; ballooning of capillaries; red
onset, often painful blood cell congestion; hemosiderin and fibro-
sis (chronic disease)
Collagenous colitis Watery diarrhea; rectal bleeding rare > 10 µm–thick subepithelial collagen band;
chronic inflammatory infiltrate
Microscopic Watery diarrhea; often seen in older Chronic inflammatory infiltrate; increased
(lymphocytic) colitis women; macroscopically normal colonic intraepithelial lymphocytes; crypt distortion
mucosa unusual
Infective colitis Sudden onset usual; identifiable source with Crypt architecture usually normal; edema;
other cases (eg, Salmonella); pain may pre- superficial neutrophil infiltrate; crypt abscesses
dominate (eg, Campylobacter); pathogens
present in stool
Pseudomembranous May be a history of antibiotics; “membrane” Similar to acute ischemic colitis but may show
colitis may be seen on sigmoidoscopy; Clostridium “summit” lesions of fibrinopurulent exudate
difficile toxin detectable in stools
Amebic colitis Travel in endemic area; amebae in fresh Similar to ulcerative colitis; amebae in lamina
stool propria or in flask-shaped ulcers; identified
by periodic acid–Schiff stain
Gonococcal colitis Rectal pain; pus Intense neutrophil infiltration; purulent exu-
date; gram-positive cocci

Adapted with permission from Jewell DP. Ulcerative colitis. In: Feldman M, Scharschmidt BF, Sleisenger MH, editors. Gastrointestinal and liver
disease. Vol. 2. Philadelphia: W.B. Saunders; 1998:1748.

of ulcerative colitis identified heavy infiltration of plas- as useful adjuncts in the classification of patients with
ma cells into the lamina propria as an independent indeterminate colitis. In the clinical context of idiopathic
predictor of more frequent flares.22 Microscopic ero- colitis, a positive p-ANCA test predicts ulcerative colitis
sions seen in macroscopically intact mucosa also have with high specificity.24 Similarly, a patient with indetermi-
been cited as a predictor of relapse.23 Further research nate colitis who has ASCA-positive serum is likely to expe-
that identifies such histologic criteria may allow sub- rience a clinical course consistent with Crohn’s disease.
groups of patients who are at high risk of relapse to be These markers are not sensitive enough to allow them to
targeted with more aggressive medical therapy. be used as screening tests in the general population. De-
termining p-ANCA and ASCA status may be more useful
• What serologic tests can be performed to distin- as a confirmatory test in a pediatric population, in which
guish ulcerative colitis from Crohn’s disease? they have been shown to have high specificity25 and in
which endoscopic evaluation is more difficult. In adults,
Serology Tests serologic tests can help predict the type of course a pa-
In the past 10 years, the perinuclear antineutrophil tient will experience and thereby aid with medical and
cytoplasmic antibody (p-ANCA) and antisaccharomyces surgical decision making. Moreover, several studies have
cerevisiae antibody (ASCA) serum assays have emerged shown that p-ANCA titers correlate with disease activity

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 Kefalides et al : Ulcerative Colitis : pp. 53 – 63

Table 3. Medications Commonly Used to Treat Ulcerative Colitis

Class/Drug Distal Colitis Mild-Moderate Moderate-Severe Maintenance

5-ASA
Enema +† +* – +
Oral +† +† – +
Corticosteroids
(classic and novel)
Enema, foam, +† +* – –
suppository
Oral +† + +† –
Intravenous +† – +† –
Immunomodulators
6-MP/AZA +† – +† +†
Methotrexate –† – – –
Cyclosporine +† – +† –

Adapted with permission from Sands BE. Therapy for inflammatory bowel disease. Gastroenterol 2000;118:S71.

ASA = aminosalicylic acid; AZA = azathioprine; 6-MP = 6-mercaptopurine.

*For adjunctive therapy.

†Selected patients.

or may predict the postsurgical complication of pouchitis Induction

in patients with ulcerative colitis who undergo colectomy Aminosalicylates that contain 5-aminosalicylic acid
and ileoanal J-pouch anastomosis.26,27 (5-ASA [mesalamine]) are the first-line agents for
inducing remission in ulcerative colitis for patients with
Diagnosis mild to moderate symptoms (Table 3). Mesalamine is
The physician makes a diagnosis of ulcerative colitis the active moiety that acts topically (from the lumen)
based on the following findings: The patient is a young to suppress the production of numerous proinflamma-
woman with recent onset of inflammatory diarrhea tory mediators.29 Aminosalicylates are available in pills,
symptoms. Her physical examination is notable for pal- suppositories, and enemas.
lor, dry oral mucosa, abdominal tenderness, and heme- The selection of an aminosalicylate agent is deter-
positive stool. Laboratory data show leukocytosis, mined by the specific sites in the large intestine to
hypoalbuminemia, and fecal leukocytes. Endoscopic which the mesalamine must be delivered; the dose
evaluation shows a left-sided colitis and biopsies reveal must be optimized to achieve clinical benefits. For-
acute and chronic inflammation. The patient’s disease tunately, these formulations have low toxicity and are
is judged to be moderately severe. generally well tolerated (Table 4). When aminosalicy-
lates are inadequate or when symptoms of ulcerative
• What is the approach to therapy in inflammatory colitis are moderate to severe, oral or topical adminis-
bowel disease? tration of corticosteroids must be used to induce remis-
sion. Prednisone 40 mg or 60 mg daily is the usual
Therapy for ulcerative colitis or Crohn’s disease starting corticosteroid. Full-dose therapy is continued
occurs in 2 steps. The first step is to induce remission until symptoms abate and bowel movements normal-
and resolve all inflammatory symptoms, and the second ize. The dose is tapered only after the patient improves
is to maintain remission. Published literature reviews of to the extent that he or she is experiencing no visible
severe ulcerative colitis suggest that approximately two blood with bowel movements and no frequency,
thirds of patients achieve clinical remission with med- urgency, or nocturnal bowel movements.
ical therapy; remission is maintained in up to 80% of When orally administered prednisone is not effec-
treatment-compliant patients.28 tive, patients must be hospitalized and started on

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 Kefalides et al : Ulcerative Colitis : pp. 53 – 63

corticosteroids, intravenously (usually methylpred- Table 4. Selected Adverse Effects of Medications

nisolone sodium succinate 40 mg daily). If the flare has Commonly Used to Treat Ulcerative Colitis
not responded after 5 to 7 days of intravenous therapy,
2 options remain: intravenously administered cyclos- Agent Adverse Effects
porine or colectomy.30 A retrospective study of 85 con- 5-ASA
secutive patients with severe ulcerative colitis, many of Sulfasalazine Anorexia, dyspepsia, nausea/vomiting;
whom had failed therapy with orally administered cor- hemolysis, neutropenia, agranulocyto-
ticosteroids, showed that those with symptoms lasting sis; folate malabsorption; reversible
more than 6 weeks or with severe endoscopic lesions male infertility; neuropathy; see also
had the highest failure rate on intravenously adminis- sulfa-free 5-ASAs
tered corticosteroids (85%).31 This patient subset re- Sulfa-free Headache; drug fever, rash; paradoxical
quired colectomy or intravenously administered cyclo- (mesalamine, exacerbation of colitis; pancreatitis;
sporine. olsalazine, hepatitis; pericarditis; pneumonitis;
balsalazide) nephritis; secretory diarrhea (olsalazine)
Maintenance
Corticosteroids
Once a patient is in remission, the goal of continued
Classic Sleep disturbance, mood disturbance,
therapy is to prevent recurrence. The level of therapy acne, striae, hirsutism, adrenal suppres-
that induced remission dictates the selection of therapy sion, proximal myopathy, glucose intol-
for maintenance. If, for example, 5-ASA compounds erance, hypertension, narrow angle
successfully controlled symptoms, then 5-ASA com- glaucoma, cataracts, pseudo-tumor
pounds will likely be adequate for maintenance cerebri, infection, edema, impaired
therapy.32 Patients with ulcerative colitis limited to the wound healing, growth retardation,
distal colon often require topical administration of osteoporosis, aseptic necrosis
mesalamine to induce remission. Many clinicians have Novel Budesonide CIR: adrenal suppression at
found that to maintain remission in these patients, the doses of 9 mg/day in 2 divided doses and
combination of oral and intermittent rectal mesalamine higher, but occurrence of classic cortico-
treatments with enemas or suppositories are necessary steroid adverse effects similar to placebo
on a long-term basis.33 If corticosteroids are necessary to Immunomodulators
induce remission, larger doses (up to 4.8 g daily) of 6-MP/AZA Nausea; drug fever, rash, arthralgia;
mesalamine may be required to prevent relapse as corti- leukopenia; thrombocytopenia; pancre-
costeroids are tapered. atitis; hepatitis; infection
Corticosteroids can induce remission in ulcerative Methotrexate Anorexia, nausea/vomiting; bone mar-
colitis but are not effective in preventing relapse. Once row suppression; megaloblastic anemia;
a disease is in remission, the daily dose of prednisone alopecia; abortifacient; hepatic fibrosis;
can be tapered on an individualized basis according to interstitial pneumonitis; neuropathy
the time required to achieve a complete resolution of Cyclosporine Reversible or irreversible decrease in
symptoms. In general, prednisone can be reduced renal function; hypertension; tremor,
weekly in 5-mg increments. headache, paresthesia, seizure; hypertri-
At referral centers for inflammatory bowel disease, chosis; hepatotoxicity; infection; lym-
clinical researchers have studied immunomodulator phoma; gingival hyperplasia
therapy with 6-mercaptopurine (6-MP) or azathio-
Adapted with permission from Sands BE. Therapy for inflammatory
prine to maintain remission in ulcerative colitis pa-
bowel disease. Gastroenterol 2000;118:S72.
tients who have been unable to taper corticosteroids,
despite mesalamine maintenance therapy. In a long- ASA = aminosalicylic acid; AZA = azathioprine; CIR = controlled ileal
release; 6-MP = 6-mercaptopurine.
term outcome study, complete remission was attained
in 65% of patients taking 6-MP and partial remission
was seen in 24%.34 Complete responders who discon- charge. Over the next several months, many experts
tinued immunomodulator therapy, however, had a suggest further transition to 6-MP or azathioprine as
high relapse rate (87%). long-term maintenance therapies, because cyclo-
If intravenously administered cyclosporine was used sporine has not been an effective maintenance treat-
to induce remission, a transition to orally administered ment. Long-term toxicities of cyclosporine include
cyclosporine is performed at the time of hospital dis- hypertension, renal insufficiency, headaches, gingival

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 Kefalides et al : Ulcerative Colitis : pp. 53 – 63

hyperplasia, and hyperkalemia. The antimetabolites Complementary Medicine Use

6-MP and azathioprine are generally better tolerated, Use of complementary medicine therapies has be-
although they are associated with a 3% to 15% inci- come increasingly common among patients with in-
dence of pancreatitis. Monitoring of a patient’s com- flammatory bowel disease. Vitamins and herbal thera-
plete blood count is required at least quarterly because pies appear to be the most popular choices. Because
of the risk for leukopenia.35 some remedies may interfere with conventional medi-
cines, it has become necessary for clinicians to question
Treatment and Follow-up patients about self-medication. In a 1998 survey of
Therapy with orally administered mesalamine at a 134 patients with Crohn’s disease or ulcerative colitis,
dose of 2.4 g daily is started in the patient, and she is 51% of patients used an alternative therapy within the
instructed to avoid NSAIDs. She is seen for follow-up prior 2 years.37 Patients were motivated by dissatisfaction
10 days later. At this visit, she reports that her symp- with adverse effects and ineffectiveness of conventional
toms have improved slightly, but her bowel movements treatments. Patients who were ill for more than 10 years
have not normalized. She still has 3 or more soft or and those with a history of hospitalization for inflamma-
sometimes liquid bowel movements daily with visible tory bowel disease were most likely to have used com-
blood. The pain has resolved, and the patient has plementary medicine. A large percentage of patients
begun to eat more. The fever has resolved as well. surveyed did not report the complementary medicine
The dose of orally administered mesalamine is use to their doctor, mostly because they perceived their
increased to 4.8 g daily, and a mesalamine enema is physicians to be ignorant or intolerant of alternative
prescribed to be taken at night. After several weeks, therapies.
symptoms of morning urgency and bleeding continue, Moser and colleagues reported similar conclusions
and the patient reports at least 6 trips to the toilet daily. from a study that correlated alternative medicine use
She is begun on orally administered prednisone 40 mg with results from a questionnaire on patients’ concerns
daily and is continued on mesalamine 4.8 g daily. about inflammatory bowel disease.38 Approximately 1 in
After 3 weeks her diarrhea has completely resolved. 3 patients with inflammatory bowel disease used an
She feels well. She reports that she has no abdominal unconventional therapy. Most used the alternative treat-
pain and that her bowel movements are formed, occur ments in conjunction with conventional medicines pre-
once daily, and have no apparent blood. scribed by their doctors. Users of complementary medi-
cine tended to have longer disease duration and were
• How long must maintenance therapy be continued more preoccupied by the prospect of surgery and feel-
in ulcerative colitis? ing out of control.
At this time, when most herbal supplements have
The optimum duration of medical maintenance not been rigorously studied and their efficacy in in-
therapy is not known. In one study, patients with ulcer- flammatory bowel disease is unknown, clinicians must
ative colitis were stratified according to their duration be aware of these trends in patients with a chronic ill-
of remission and randomized to receive mesalamine or ness such as ulcerative colitis. These studies reinforce
placebo for 1 year.36 Mesalamine was more effective at the importance of taking a thorough medication histo-
maintaining remission in patients who had a shorter ry and allowing inflammatory bowel disease patients to
duration of remission (mesalamine 23% recurrence, actively participate in medical decision making.
placebo 49% recurrence). However, among the pa-
tients with a longer duration of remission at study • What surgical procedures are used in ulcerative coli-
entry, there was no statistical difference in the rate or tis, and when is surgery indicated?
relapse. This research suggests that patients with mild
ulcerative colitis may not need indefinite maintenance Surgery
therapy once they have been in remission for several Surgery is curative in ulcerative colitis and has been
years. In general, however, patients with inflammatory shown to lead to durable improvements in quality of
bowel disease must be compliant with maintenance life.39 Several surgical options exist. The 2 most com-
medical therapy in order to decrease the likelihood of mon choices today are proctocolectomy with ileostomy
recurrent flares. and total colectomy with ileoanal anastomosis. In previ-
ous years, total colectomy with ileorectal anastomosis
• How is alternative or complementary medicine has been performed as well as proctocolectomy with
changing the management of ulcerative colitis? the Kock pouch—a continent ileostomy.

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 Kefalides et al : Ulcerative Colitis : pp. 53 – 63

Elective surgery in ulcerative colitis can be done symptoms. In general, these extraintestinal manifesta-
laparoscopically. The advantages of the laparoscopic tions of ulcerative colitis respond to the treatment of
approach are a shorter postoperative ileus and less nar- the disease.20
cotic requirement. Patients can generally be fed sooner, The principal long-term complications of ulcerative
and shorter hospital stays have been reported.40 colitis are colorectal cancer and primary sclerosing
Colectomy is indicated in ulcerative colitis that is cholangitis. The risk for colon cancer in a patient with
refractory to medical therapies or when it is fulminant ulcerative colitis rises exponentially as the duration of
and toxic megacolon or perforation is suspected. disease increases. The annual rate of development of
Approximately 25% of patients with severe colitis will colorectal cancer has been estimated to be 2% after
fail to improve from therapy with intravenously admin- 20 years of disease and 8% after 30 years. Persons who
istered corticosteroids and will require urgent colecto- develop ulcerative colitis later in life are thought to be
my.41 Clinical signs that suggest failing medical therapy at an even higher risk.42
include cessation of bowel movements, abdominal dis- Current practice guidelines recommend that surveil-
tension, progressive leukocytosis, and progressive hypo- lance for colorectal cancer begin after the tenth year of
albuminemia. Surgery should be offered to all patients disease, regardless of the level of disease activity.
with severe symptoms who do not improve within a Colonoscopy with random biopsies is recommended at
week of treatment with intravenously administered cor- 2-year intervals. If there is any microscopic evidence of
ticosteroids. A final indication for surgery is the devel- dysplasia in areas of the colon affected by ulcerative coli-
opment of dysplasia or cancer. tis, the patient should undergo prophylactic colectomy.43
Cancerous lesions in ulcerative colitis may be occult,
Two Years Later and some experts advocate consideration of elective pro-
At a follow-up visit 2 years after diagnosis of ulcerative phylactic colectomy in any patient with a long disease
colitis, the patient reports having mild flares of her duration. In a series of 493 patients with an average
symptoms that she manages with short-term treatment duration of illness of 18.5 years who underwent colecto-
with nightly mesalamine enemas. In general, the ulcera- my and were found to have cancer, 12% had no preop-
tive colitis has remained well controlled with orally erative evidence of malignancy.44 Our preference is to
administered mesalamine. She has new symptoms of hip enroll patients with disease in a surveillance program
and knee pain that correlate with her flares of colitis. In that consists of colonoscopy every 2 years with multiple
addition, her aunt was recently diagnosed with colon random biopsies at 10-cm intervals throughout the
cancer, and she is concerned about her own risk. colon. This screening begins 10 years after diagnosis. We
do not advocate routine prophylactic colectomies.
• What are the complications of ulcerative colitis? Primary sclerosing cholangitis occurs in approxi-
mately 3% of ulcerative colitis patients. Chronic inflam-
Complications of Ulcerative Colitis mation of the biliary system leads to cholestasis, intra-
There are several extraintestinal manifestations of hepatic and extrahepatic biliary obstruction, and,
ulcerative colitis. Inflammatory changes can be seen in eventually, cirrhosis. Endoscopic cholangiography and
the oral mucosa, where aphthae are seen in approxi- liver biopsy can confirm the diagnosis. Treatments
mately 10% of patients experiencing an acute flare. include endoscopic decompression of dominant extra-
The skin may also be involved in ulcerative colitis. hepatic biliary strictures and supportive care for compli-
Erythema nodosum may complicate ulcerative colitis or cations of liver disease. Therapy with ursodeoxycholic
herald a flare of the disease. Pyoderma gangrenosum is acid can provide symptomatic relief from pruritus and
an ulcerating skin condition that affects the trunk and may slow the progression of the biliary inflammation.
limbs of only 1% to 2% of these patients. The skin Interestingly, a recent cross-sectional study showed that
lesions parallel the severity of colonic inflammation and patients with ulcerative colitis who had primary scleros-
only rarely persist in the setting of quiescent colitis or ing cholangitis treated with ursodeoxycholic acid had
after colectomy. Episcleritis or anterior uveitis is seen in less colonic dysplasia, suggesting that ursodeoxycholic
5% to 8% of patients. Scleral inflammation is most com- acid may have a chemopreventive effect in the colon.45
monly associated with flares of colitis, whereas uveitis Primary sclerosing cholangitis is a strong risk factor for
(iritis) is associated with HLA B-27 and runs a course the development of cholangiocarcinoma. All dominant
independent from colitis activity. Asymmetric, large biliary strictures should be sampled cytologically or eval-
joint arthritis with swelling but without erosion compli- uated by intraductal endosonography to afford early
cates approximately 10% to 15% of patients with acute diagnosis of malignancy.

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 Kefalides et al : Ulcerative Colitis : pp. 53 – 63

Physician’s Recommendations 10. Batts KP, Weiland L. Pathology of ulcerative colitis.

The physician reassures the patient that the joint Semin Colon Gastroenterol 1990;1:132–46.
11. Leichtner AM, Jackson WD, Grand RJ. Ulcerative colitis.
pains she is feeling is related to her intestinal inflamma-
In: Walker WA, Durie PR, Hamilton JR, et al, editors.
tion and should improve with treatment of the colitis.
Pediatric gastrointestinal disease: pathophysiology, diag-
He also explains that her risk of colorectal cancer will nosis, management. 2nd ed. St. Louis: Mosby; 1996:
ultimately be even higher than that of other patients 712–23.
with ulcerative colitis because she has a first-degree rela- 12. Treem WR, Cohen J, Davis PM, et al. Cyclosporine for
tive with colorectal cancer. The physician recommends the treatment of fulminant ulcerative colitis in children.
full colonoscopy after 10 years of ulcerative colitis, or Immediate response, long-term results, and impact of
sooner if the patient has new symptoms or a clinical surgery. Dis Colon Rectum 1995;38:474–9.
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North Am 1996;43:235–54.
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of glucocorticoids in children. Pediatr Rev 1995;16:
Ulcerative colitis is a chronic inflammatory condi-
266–72.
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span but can cause significant morbidity and lead to nomics review: medical management of inflammatory
considerable expense. Before establishing the diagno- bowel disease. Aliment Pharmacol Ther 1999;13:15–25.
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bowel disease. Eur J Gastroenterol Hepatol 2000;12:
Over the long term, screening for neoplastic and
855–62.
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