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Summary
Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) characterized by
chronic mucosal inflammation of the rectum, colon, and cecum. Common symptoms include
bloody diarrhea, abdominal pain, and fever. Laboratory findings typically show elevated inflammatory
markers and the presence of autoantibodies (pANCA). Definitive diagnosis requires biopsies showing
abnormal colonic mucosa and characteristic histopathology. Aminosalicylic acid derivatives are the
mainstay of treatment, although severe episodes typically
require corticosteroids and immunosuppressants to achieve remission. In the case of distal colitis, some
drugs may be administered topically (e.g., via enema), whereas more proximal inflammation requires
systemic treatment. Proctocolectomy is curative and indicated for complicated UC or dysplasia. Individuals
with UC are predisposed to colorectal cancer and should thus undergo regular surveillance colonoscopy.
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Epidemiology
Prevalence
o Approx. 600,000 adults in the U.S. are affected by UC [1]
o Ethnicity
Higher in the white than in the black, Hispanic, or Asian populations
Highest among individuals of Ashkenazi Jewish descent.
o Slightly higher in men than women [2]
Peak incidence
o 15–35 years [3]
o Another smaller peak may be observed in individuals > 55 years [4]
References: [2][4][5]
Epidemiological data refers to the US, unless otherwise specified.
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Classification
Truelove and Witts severity index [6]
MAXIMIZE TABLETABLE QUIZ
Criteria Mild Moderate Severe
Imaging [3][14]
Imaging studies may serve as useful adjunct diagnostic procedures for UC, particularly when it comes
to detecting complications.
Radiography
o Plain radiography
Typically normal in mild to moderate disease
Findings
Loss of colonic haustra (lead pipe appearance) may be seen in severe cases
Massive distention in cases of toxic megacolon
Pneumoperitoneum in cases of perforation
o Barium enema radiography
Able to detect very early changes
Findings
Granular appearance of the mucosa
Deep ulcerations
Loss of haustra
Pseudopolyps that appear as filling defects
CT: Detection of bowel wall thickening is possible in severe disease.
MRI: can be helpful in assessing disease severity and extent of bowel wall involvement
Ultrasound: can detect bowel wall thickening (manifests with absent hyperechoic reflection from
the lumen)
References:[12][13][15]
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Pathology
Gross pathology
Early stages
o Inflamed, erythematous, edematous mucosa
o Friable mucosa with bleeding on contact with endoscope
o Fibrin-covered ulcers
o Small mucosal ulcerations
o Loss of superficial vascular pattern
Chronic disease
o Loss of mucosal folds
o Loss of haustra
o Strictures
o Deep ulcerations
o Pseudopolyps
Raised areas of normal mucosal tissue that result from repeated cycles of ulceration
and healing
Ulceration → formation of granulation tissue → deposition of granulation tissue
→ epithelization
Morphologically resemble polyps but do not undergo neoplastic transformation
Found in advanced disease
In ulcerative colitis, the extent of intestinal inflammation is limited to the mucosa and submucosa. In
contrast, Crohn disease shows a transmural pattern of intestinal involvement.
Histological findings
Early stages
o Granulocyte (neutrophil) infiltration: limited to mucosa and submucosa
o Crypt abscesses: an infiltration of neutrophils into the lumen of intestinal crypts due to a
breakdown of the crypt epithelium
Chronic disease
o Lymphocyte infiltration
o Mucosal atrophy
o Altered crypt architecture
Branching of crypts
Irregularities in size and shape
o Epithelial dysplasia
Noncaseating granulomas are seen in Crohn disease but are not a feature of ulcerative colitis!
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Differential diagnoses
Differential diagnosis considerations
Crohn disease (see “Differential diagnostic considerations: Crohn disease and ulcerative colitis”)
Exudative-inflammatory diarrhea
Diverticular disease
Appendicitis
Ischemic colitis
Infectious colitis
o C. difficile colitis
o Shigella dysenteriae
o Salmonella enterocolitis
o Escherichia coli colitis
o Campylobacter enterocolitis
o Yersiniosis
o Tuberculosis
o CMV colitis
Radiation colitis
Celiac disease
Inflammatory diarrhea
Microscopic colitis
Definition: An idiopathic form of colitis that is characterized by a normal macroscopic appearance
of bowel on colonoscopy and collagenous or lymphocytic infiltrates on microscopy.
Forms: collagenous colitis and lymphocytic colitis
Etiology: unknown
Clinical findings
o Chronic, nonbloody, watery diarrhea for > 4 weeks
o Weight loss
o Abdominal pain
Pathological findings
o Gross pathology: normal appearance
o Histology
Collagenous colitis: proliferation of collagenous connective tissue
Lymphocytic colitis: mainly lymphocytic infiltrates with
little/no proliferation of connective tissue
Treatment
o Cease nonsteroidal anti-inflammatory drugs (NSAIDs may be a trigger for disease)
o Symptomatic therapy (e.g., loperamide for mild diarrhea)
o Corticosteroids
The differential diagnoses listed here are not exhaustive.
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Treatment
Initially, UC is treated conservatively with drugs to induce and maintain disease remission.
Curative proctocolectomy is generally indicated if medical therapy fails or complications arise.
General management
Rehydration
Supplementation of nutritional deficiencies (e.g., iron)
Supplementation of nutrition: severe cases may warrant consideration of a feeding tube
or parenteral nutrition.
Medical therapy [3]
Supportive care
Antidiarrheal agents (e.g., loperamide): can only be used in the absence of a flare
Anticholinergic medication (e.g., propantheline, dicyclomine): relieves abdominal cramping
NSAIDs, opioids, and anticholinergics should be avoided in severe disease.
Mild disease
5-aminosalicylic acid derivatives (5-ASAs)
o Drugs
Mesalamine
Sulfasalazine
Olsalazine (compound of two 5-ASA molecules)
o Mechanism of action
5-ASA alone (mesalamine) or bound to sulfapyridine as a carrier (sulfasalazine)
Sulfasalazine is activated by colon bacteria
5-ASA: antiinflammatory, immunosuppressive
Sulfapyridine: antibacterial
o Indications
Ulcerative colitis
Colitis component of Crohn disease
o Side effects
Mesalamine
GI irritation: nausea, diarrhea
In rare cases: peripheral
neuropathy, myocarditis or pericarditis, myelosuppression
Sulfasalazine
Most of the side effects are caused by the sulfapyridine
component of sulfasalazine.
GI irritation: nausea, diarrhea
Headache, fatigue, malaise, depression
Megaloblastic anemia and folate deficiency due to interference
with dihydropteroate synthase
Immune thrombocytopenia [16]
Transient oligospermia
Sulfa drug: allergic reactions, sulfonamide toxicity
o Drug interactions: coadministration of nephrotoxic
drugs (e.g. NSAIDs, aminoglycosides, lithium) → ↑ risk of renal impairment
o Additional information
Can be administered orally, as suppositories,
or as enemas
Sulfapyridine has proven to have beneficial effects in patients with rheumatic
disease.
If no improvement or 5-ASA agents are not tolerated
o Topical corticosteroids (e.g., budesonide)
o Oral systemic corticosteroids
Moderate disease
Oral and topical 5-ASAs
Topical corticosteroids (e.g., budesonide) → systemic corticosteroids only if no response
Anti-TNF therapy (adalimumab, golimumab, or infliximab)
Vedolizumab (integrin receptor antagonist)
Tofacitinib (JAK3 inhibitor)
Severe or refractory disease
High-dose oral and topical 5-ASAs
Systemic corticosteroids
Anti-TNF therapy (e.g., adalimumab, golimumab, or infliximab)
Calcineurin antagonists (e.g., cyclosporine, tacrolimus)
Thiopurines (6-mercaptopurine, azathioprine) may be considered but are no longer recommended
as monotherapy due to lack of efficacy [3]
Vedolizumab (integrin receptor antagonist)
Tofacitinib (JAK3 inhibitor)
Referral for surgical proctocolectomy (see below)
Systemic corticosteroids should only be used for the treatment of an active flare and are not
recommended as a maintenance medication for ulcerative colitis.
Surgical intervention
Goal
o Curative approach with full recovery
o Reduce risk of colorectal cancer
Indications
o Emergent: Acute complications despite adequate conservative management (e.g., toxic
megacolon, perforation, sepsis, uncontrolled bleeding, etc.)
o Elective: epithelial dysplasia, severe relapses, long-term dependence on steroids,
impairment of the patient's general condition
Procedure: proctocolectomy with an ileal pouch-anal anastomosis (IPAA or J pouch)
o Resection of the entire colon and rectal mucosa while sparing the anal sphincters.
o Loops of small intestine (serving as the pouch) are used to create an
artificial rectum (reservoir for feces) and thus a continence-conserving connection between
the ileum and anus.
Complications
o Anastomotic leak
o Pouchitis (↑ stool frequency, malaise, and possibly incontinence caused by bacterial
overgrowth)
In contrast to Crohn disease, ulcerative colitis can be cured surgically (proctocolectomy).
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Complications
Gastrointestinal bleeding (both acute and chronic)
Toxic megacolon
Perforation → peritonitis (see “Gastrointestinal perforation”)
Fulminant colitis: severe bowel inflammation that typically causes > 10 stools per day, lower
gastrointestinal bleeding, abdominal pain, and abdominal distention
↑ Risk of cancer (see ”Colorectal carcinoma”)
o Risk increases with increased duration and/or extent of disease (e.g., pancolitis).
o Risk is not significantly increased in patients with mild UC
o Prevention: Screening colonoscopy with biopsies every 1–3 years starting 8 years after the
initial diagnosis to screen for colorectal cancer
[3]
Colonic stricture
Amyloidosis