ULCERATIVE COLITIS
DEFINITION:
An inflammatory disease primarily of the colon and rectum
characterized by diarrhea, rectal bleeding, and abdominal pain.
EPIDEMIOLOGY:
- incidence: 2.3/100,000 (for those 10-19 years of age)
- age of onset:
- only 20% diagnosed before the age of 20 (rare before age 5
years)
- risk factors:
- M = F
- whites > blacks
- Jews
- North America, Scandinavia, Europe
PATHOGENESIS:
- like Crohn's Disease, expression of the disease seems to be
dependent upon a susceptible host being exposed to specific
triggers:
- increased incidence (5-29%) of Ulcerative Colitis (UC)
in 1st degree relatives with siblings the most likely to be
affected
- 6.3% concordance rate in twin studies
2. Specific Triggers
- antineutrophil cytoplasmic antibodies may play a role
- there is no convincing evidence to implicate a
particular bacteria, mycobacteria, virus, or protazoan
- cow's milk protein sensitivity probably does not play a
consistent role
CLINICAL FEATURES:
- diarrhea (93%)
- rectal bleeding or abdominal pain (86%)
- weakness (67%)
- weight loss (51%)
- nausea/vomiting (42%)
- fever (37%)
1. Diarrhea
- in 50% there is an insidious onset of mild diarrhea and
rectal bleeding with intermittent low grade fever and mild
abdominal pain
- in 33% there is a dramatic onset of bloody diarrhea,
tenesmus, urgency, low grade fever, weight loss, and anemia
- in 10% there is a fulminant onset with up to 6 bloody
stools per day with fever, weight loss, and tachycardia
2. Gastrointestinal Complications
- massive acute GI bleed in 3% of patients
2. Stricture
- most common in the sigmoid colon and rectum
- 2-3 cm in length
- usually due to hypertrophy and thickening of the
muscularis mucosae (but should rule out cancer)
3. Perforation
- can occur with moderately severe disease, severe
fulminant colitis, or with toxic megacolon
- usually involves the left colon
- results in free air in the abdominal cavity +/-
peritonitis
4. Toxic Megacolon
- an acute, life-threatening dilatation of the colon
occurring in 3-5% of patients
- risk factors:
- 1st attack of colitis
- duration of disease <5 yrs
- pancolitis
- recent barium enema or colonoscopy
- severe disease
- use of opiates or anticholinergic meds
- severe transmural inflammation -> smooth muscle
destruction
- aperistalsis -> dilatation of the colon -> perforation +
systemic toxicity
- usually develops over hours to days with abdominal
distension and signs of toxicity
- transverse colon and splenic flexure most often affected
5. Carcinoma
- lifetime risk of developing colon cancer is 15% (in the
general population is 5%)
- increased risk with increased duration & extent of
disease
- usually adenocarcinomas evenly distributed throughout
the colon
3. Extraintestinal Manifestations
- hepatomegaly
- fatty liver
- chronic hepatitis
- cirrhosis
2. Biliary
- pericholangitis
- primary sclerosing cholangitis
2. Renal (5%)
3. Rheumatoid
- arthralgias and arthritis (10%)
- migratory, asymmetric arthritis affecting the large
joints of the lower extremities
- non-deforming and activity of the joint disease
parallels the activity of the bowel disease
- ankylosing spondylitis (6%)
- course tends to be independent of the bowel disease
4. Cutaneous (<5%)
- erythema nodosum
- pyoderma gangrenosum
5. Ocular
- episcleritis
- corneal ulcerations
- cataracts
- keratopathy
- uveitis
- posterior subcapsular cataracts (steroid therapy)
6. Vascular
- thrombocytosis with vascular complications (1.3%)
- deep vein thrombosis
- pulmonary embolism
- vasculitis (cerebral)
INVESTIGATIONS:
- affected area is continuous from the rectum proximally
- rectal sparing is unusual
- early - diffuse erythema with contact bleeding
(friability)
- late - granular mucosa; numerous small surface ulcerations
covered with inflammatory exudate; flat, deep mucosal ulcers;
pseudopolyps
2. Microscopic
- inflammation within the:
- crypts - neutrophils and crypt abscesses
- lamina propria - lymphocytes, eosinophils, and mast
cells
- occasionally spreads to the submucosa & serosa
- depleted goblet cell mucin
2. Imaging Studies
- less sensitive than Double Contrast
2. Double Contrast (Air-Barium)
- early - granular appearance (like fine or coarse
sandpaper)
- later - irregular serrated bowel contour
- 'collar button' ulcerations
- pseudopolyp formation
- loss of haustration ('stove pipe' tube)
2. Abdominal X-Ray
- thumbprinting from mucosal edema
- dilated colon (>8 cm)
3. Serum
- microcytic hypochromic anemia, leukocytosis,
thrombocytosis
2. Others
- hypoalbuminemia
- elevated ESR and acute phase reactants
4. Stools
- guaiac-positive
- negative for pathogens
MANAGEMENT:
- diagnosis, definition, epidemiology, prognosis, treatment
options
3. Goals of Therapy
- medical therapy is not curative but to control symptoms,
prevent complications, improve growth, and to induce remission
- surgical therapy is curative
4. Management Strategies
- a prodrug composed of 5-ASA + sulfapyridine (split in
the colon by anaerobic bacteria)
- only 10% absorbed so most delivered to the small bowel
and colon
- an anti-inflammatory agent by decreasing prostaglandin
and leukotriene synthesis
- indicated for mild-moderate ulcerative colitis
- start at 25 mg/kg/day po tid-tid and increase over 7-10
days to 40-60 mg/kg/day
- maintenance therapy
- use up to 2 gm/day
- maintains remission and prevents relapses
- may be used for one or more years
- side effects may be due to the sulfapyridine moiety
- side effects: anorexia, nausea/vomiting, myalagias,
arthralgias (each dose-related); hypersensitivity - fever,
rash, arthritis, pericarditis, pleuritis, pancreatitis,
hepatitis, autoimmune anemia, bloody diar-rhea, acute
colitis (reverse with discontinuation); reversible
oligospermia; megaloblastic anemia (interferes with folate
absorption)
- follow CBC, amylase, liver function tests, and folate
2. Aminosalicylates (5-ASA)
- delayed-release acrylic coating that dissolves at a
specific pH thus increasing delivery of 5-ASA to the
distal small bowel and colon
- fewer side effects than with sulfasalazine
- watery diarrhea in 10-30%; nephrotoxic
- ? role in childhood UC
2. Topical - Mesalamine (Rowsa)
- indicated for distal colitis & proctosigmoiditis
- given as an enema or suppository and may play a role
in the treatment of active disease and/or maintenance of
remission
- Mesalamine enemas 4 gm qhs x 6 weeks for acute
episodes
- side effects: anal irritation, pancreatitis
3. Prednisone
- indicated for acute episodes in addition to maintenance
sulfasalazine therapy
- an anti-inflammatory agent which increases the synthesis
of inflammatory-modulating proteins
- 1-2 mg/kg/day po od (max. 40-60 mg/day) x 2-3 weeks then
decrease by 5 mg/week
- effects of too rapid a withdrawal: acute adrenal
insufficiency, pseudotumor cerebri with papilledema - see "Crohn's
Disease" file for side effects
- may also use IV steroid (methylprednisolone) or enemas
(hydrocortisone)
4. Immunosuppressive Agents
- indicated as corticosteroid-sparing agents in a
subgroup of children with intractable chronic UC -
Azathioprine 2 mg/kg/day
- side effects: nausea/vomiting, hair loss, transient
peripheral neuropathy, pancreatitis, bone marrow
suppression (moniter CBC every month)
2. Cyclosporin A
- suppresses T-cell function
- experience in paediatric UC is limited
3. Methotrexate
- folic acid antagonist
- experience in paediatric UC is limited
2. Supportive Therapy
2. Diet
- TPN +/- elemental diet for acute episodes and in
nutritionally depleted patients
3. Metronidazole
3. Surgery
- curative
- indications for surgery:
- failure of medical therapy
- hemorrhage, performation, toxic megacolon
2. Elective
- chonic ill health and/or steroid dependence
- high-grade dysplasia or malignancy
5. Prognosis
- most patients with UC have mild-to-moderate disease which
can be medically mananged:
- single episode only (10%)
- intermittent symptoms (10%)
- chronic symptoms; not incapacitating (50%)
- chronic symptoms; incapacitating (20%)
- 30% colectomy rate
- increased risk with pancolitis
- 33% of those with proctosigmoiditis have proximal
extenison of the disease
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