UC is a chronic inflammatory disease affect the
mucosa of the large intestine, usually begins at rectum and extends proximally
(just 5% of cases without rectum involvement, third of cases in pediatric
onset).
It is characterized by recurring episodes of
inflammation with periods of remissions, some patients have persistent disease
activity, and a small number of patients present with fulminant disease
Epidemiology
The condition may present at any time and at
all ages, but there is a predominant age distribution of onset that peaks
between ages 15 and 30 years.
In North America, incidence rates range from
2.2 to 19.2 cases per 100,000 person-years
Clinical manifestation
-
Diarrhea with/without blood
-
colicky abdominal pain, urgency, tenesmus, and
incontinence
-
Patients with mainly distal disease may have constipation
accompanied by frequent discharge of blood and mucus.
-
systemic symptoms including fever, fatigue, and weight loss.
-
Complications such as anemia due to bleeding and iron
deficiency with palpitations, dyspnea.
Disease activity: The severity of disease activity can be
objectively measured using a clinical disease activity index, such as the 1- Montreal
classification of severity of ulcerative colitis:
- Mild:
-
four or fewer stools per
day with or without blood
-
no signs of systemic
toxicity
-
normal erythrocyte
sedimentation rate (ESR).
-
Mild crampy pain, tenesmus,
and periods of constipation
-
severe abdominal pain,
profuse bleeding, fever, and weight loss are not part of the spectrum of mild
disease.
- Moderate:
-
Frequent loose, bloody
stools (>4 per day)
-
Patients have minimal signs
of systemic toxicity, including a low-grade fever.
-
mild anemia not requiring
blood transfusions
-
abdominal pain that is not
severe.
-
Adequate nutrition is
usually maintained, and weight loss is not associated with moderate clinical disease.
- Severe:
-
frequent loose bloody
stools (≥6 per day)
-
severe cramps
-
evidence of systemic
toxicity as demonstrated by a fever (temperature ≥37.5ºC), tachycardia (HR
≥90 beats/minute), anemia (hemoglobin <10.5 g/dL), or an
elevated ESR (≥30 mm/hour).
-
Patients may have rapid
weight loss.
Other scores to estimate the severity of UC 2- MAYO-Score:
![]() |
Source: ACG Clinical Guideline: Ulcerative Colitis in Adults |
Extraintestinal manifestations: present
in up to 25% of patients:
·
Musculoskeletal:
-
nondestructive Arthritis
which primarily involves large joints
-
ankylosing spondylitis.
-
osteoporosis, osteopenia,
and osteonecrosis.
·
Eye:
-
uveitis and episcleritis
-
Scleritis, iritis, and
conjunctivitis
·
Skin
-
erythema nodosum
-
pyoderma gangrenosum
·
Hepatobiliary:
-
Primary sclerosing
cholangitis
-
fatty liver
-
autoimmune liver
·
Hematopoietic/coagulation:
-
increased risk for both
venous and arterial
-
Autoimmune hemolytic anemia
(AIHA) has been associated with IBD.
Diagnosis
·
History:
-
recent
travel to areas endemic for parasitic infections: amebiasis?
-
recent
antibiotic use: Clostridium difficile?
-
Sexual
anamneses: sexually transmitted diseases? Neisseria gonorrhea and herpes
simplex virus (HSV) are associated with proctitis!
-
Atherosclerotic
disease or prior ischemic episodes: chronic colonic ischemia?
-
history
of abdominal/pelvic radiation and NSAID/medication
-
In an immunocompromised
patient, cytomegalovirus (CMV) can mimic ulcerative colitis.
·
Laboratory:
-
HGB: anemia? iron
deficiency? Signs of hemolysis?
-
ESR, CRP: elevated?
-
Electrolyte: abnormalities
due to diarrhea
-
Kidney and lever functions
tests
-
APH: elevated by PSC
-
pANCA may be elevated but
its rule in the diagnosis is unclear
·
Stool tests:
-
Clostridium difficile toxin
-
stool cultures (Salmonella,
Shigella, Campylobacter, Yersinia, and specific E. coli 0157:H7)
-
Microscopy
for ova and parasites (three samples)
-
Giardia
stool antigen test
-
Calprotectin:
elevated
·
Serologic testing for
sexually transmitted diseases
-
Neisseria
gonorrhea
-
HSV
-
Treponema
pallidum
-
CMV by
Immunosuppressed
·
Coloscopy:
-
Colonoscopy with intubation of the ileum and biopsies of
affected and unaffected areas should be obtained
-
Extend of the disease: according to Montreal classification:
1- (E1) proctitis
(within 18 cm of the anal verge, distal to the rectosigmoid junction) 30-50%
2- (E2) left-sided
colitis (extending from the sigmoid to the splenic flexure), 20-30%
3- (E3) extensive
colitis (beyond the splenic flexure). 20%
-
Endoscopic
severity of UC can be evaluated with different indexes, such as Ulcerative Colitis Endoscopic Index of Severity UCEIS:
![]() |
Source: ACG Clinical Guideline: Ulcerative Colitis in Adults |
-
The
biopsy features suggestive of ulcerative colitis include:
Crypt abscesses, and crypt
atrophy.
Increased lamina propria
cellularity
Basal plasmacytosis, basal
lymphoid aggregates
Lamina propria eosinophils.
None of these features are
specific for ulcerative colitis, the presence of two or more histologic
features is highly suggestive of ulcerative colitis
Differential Diagnosis
- Crohn's disease: Features that
are suggestive of Crohn’s disease include absence of gross bleeding,
presence of perianal disease (eg, anal fissures, anorectal abscess), and
fistulas. The absence of rectal inflammation and the presence of ileitis,
focal inflammation, and granulomas on endoscopy and biopsy are also
suggestive of Crohn’s disease.
- Infectious
colitis:
stool and tissue cultures.
- Radiation
colitis: Radiation
colitis may be seen weeks to years after abdominal or pelvic irradiation.
histologic findings suggestive of radiation colitis include eosinophilic
infiltrates, epithelial atypia, fibrosis, and capillary telangiectasia.
- Solitary rectal
ulcer syndrome: Patients
with solitary rectal ulcer syndrome may have bleeding, abdominal pain, and
altered bowel habits. Mucosal ulceration may be seen on endoscopy similar
to ulcerative colitis, but solitary rectal ulcer syndrome has a
characteristic appearance on histology with a thickened mucosal layer and
distortion of crypt architecture. The lamina propria is replaced with
smooth muscle and collagen leading to hypertrophy and disorganization of
the muscularis mucosa.
- Graft versus
host disease:
Graft versus host disease (GVHD) of the colon can cause chronic diarrhea
in patients with a history of bone marrow transplantation. Patients may
have symptoms due to involvement of other organs (eg, liver). Histologic
examination in chronic GVHD is characterized by the presence of crypt
cell necrosis with the accumulation of degenerative material in the
dead crypts.
- Medication
associated colitis: Nonsteroidal anti-inflammatory drugs (NSAIDs) can cause
chronic diarrhea and bleeding. The
diagnosis is established by a history of medication use and the presence
of nonspecific mucosal inflammation or mucosal erosions on biopsy that
resemble ischemic changes.
Therapy
therapy has two goals: to induce remission and to maintain it.
Therapeutic management in UC should be guided by assessment of
disease activity (i.e., mild, moderate, or severe), and disease prognosis.
Mild diseased patients with bad prognose factors are to be treated
as severe diseased patients.
1-
mildly active UC:
-
Proctitis: rectal
5-ASA 1g/d
-
Left-sided UC:
5-ASA Enema 1 g/d alone or in combination with oral 5-ASA 2 g/d, by intolerance
or nonresponsive: oral budesonide multi-matrix (MMX) 9 mg/d.
-
Extensive UC: oral
5-ASA 2 g/d.
-
higher
dosage of 5-ASA has no more difference
in the remission rate
-
Symptomatic improvement and a decrease in bleeding can be
seen within a few days.
Maintenance of remission in patients with previously mildly active
UC:
-
Proctitis: rectal 5-ASA 1g/d
-
Left-sided/Extensive colitis: oral 5-ASA 2 g/d.
2-
MODERATELY TO SEVERELY ACTIVE UC:
-
Systemic steroids: Prednisolone 30 mg x2/d or budesonide multi-matrix
(MMX) 9 mg/d.
-
Oral 5-ASA as combination therapy with steroids: 4.8g/d
-
Local 5-ASA/Steroids may help
Caution: 5-ASA may cause Exacerbation of the disease
in some rare cases, and should be discontinued
-
When
systemic toxicity with fever è
consider antibiotics: Ciprofloxacin+ Metronidazole
-
When no meaningful clinical response after 7-10 days
of intravenous therapy with steroids è consider
anti-TNF: Infliximab
Maintenance of remission in patients with MODERATELY TO SEVERELY ACTIVE UC:
-
Begin steroid taper 2-4 weeks after patient has been stabile
-
Taper Steroid over 8 weeks: 10 mg/week until 20 mg/d then
2.5/week
-
Local steroids/5-ASA should be tapered over 2-4 months
-
Oral 5-ASA should be continued at the same dose 4.8 g/d
When: (
1-
Steroid-dependent:
-
glucocorticoids cannot be tapered to less than 10 mg/day within three months of starting glucocorticoids
without recurrent disease
-
or relapse occurs within 3 months
of stopping glucocorticoids.
2-
Steroid-refractory:
-
No significant response on steroid 40-60 mg p.o. within 30
days
-
Or 40-60 mg i.v. within 7-10 days
3-
Severe ulcerative colitis with >2 relapses requiring glucocorticoids
in 12 months despite optimal doses of oral 5-ASA medication
or
4-
Patients who cannot tolerate 5-ASA.
è consider: 6-mercaptopurine (6-MP)/ azathioprine (AZA) or an anti-TNF agent for maintenance of remission:
1- AZA: 2 mg/kg/day WHEN patient take steroid and benefit
from it (dependent) è Steroid reduction after 2-4 weeks due to the
schemata above. AZA takes 3-6 months till effect.
2- When Steroid-refractory then the patient can’t wait
till AZA takes its effect è fast-acting Agent Cyclosporine: 2-4 mg/kg/day as
continuous infusion
-
Effect to be seen after 3 days: (no pain, consistent stools,
patients can eat)
-
Then give it as oral therapy with the double doses 4-8 mg/kg
divided om 2 time a day
-
Continue steroid therapy as above (oral) with successive reduction
after 4-6 weeks of begin
-
Start reduction of cyclosporin after 6-8 weeks of begin
-
Begin AZA 2mg/kg/day therapy 1 week after beginning with oral
cyclosporin therapy.
-
Cyclosporin levels in blood should be taken every 2-3 days: by
4 mg/kg i.v. 300-400 ng/ml, by oral therapy 200-300 ng/ml, under 200 ng/ml no
response
3- When AZA is not an option due to allergy or has already
failed then a bridge therapy with cyclosporin has no Sinn è
Infliximab: can be used to both initiation a remission and maintain it. 5-10
mg/kg at week 0.2.6 and then every 8 weeks.
Surgical therapy:
20-30% of Patients will require OP.
If:
-
Cyclosporin fails to achieve improvement in 3 days of i.v.
therapy
-
Infliximab fails to achieve remission
-
Side effects of medication are intolerable
-
Dysplasia or Coloncancer
-
Acute fulminant UC with acute Abdomen
-
Acute fulminant UC without acute Abdomen, when
Cyclosporin/Infliximab fails to induce Remission within 4-7 days, or by toxic
megacolon within 3 days.
ð Consider Colectomy
3- FULMINANT ULCERATIVE COLITIS:
Fulminant
colitis is subgroup severe ulcerative colitis with:
-
> 10 stools per day
-
continuous bleeding
-
abdominal pain, distension
-
acute, severe toxic symptoms including fever and anorexia.
-
risk of progressing to toxic megacolon and bowel perforation.
Therapy:
-
Admission to a hospital
-
vital signs and physical examination every four to six hours
-
A complete blood count, serum electrolytes, serum albumin,
liver function tests, and erythrocyte sedimentation rate (ESR) or C-reactive
protein (CRP) should be checked every 12 to 24
-
Patients should be kept NPO. Nutritional support should be
considered if the patient is malnourished.
-
Intravenous fluid and electrolyte replacement are necessary
to correct and prevent dehydration or electrolyte imbalance.
-
Blood transfusions may be needed to maintain a hemoglobin
≥10 g/dL.
-
Patients with intestinal dilation (transverse colon diameter
≥5.5 cm) should receive decompression with a nasoenteric tube. Intermittent
rolling maneuvers every two hours or the knee-elbow position should be
recommended.
-
Plain abdominal radiography should be repeated if there is
clinical deterioration to determine if there is colonic dilation (diameter ≥5.5
cm) or toxic megacolon (diameter ≥6 cm or cecum >9 cm and systemic
toxicity).
-
intravenous glucocorticoids. Prednisolone (30 mg IV
every 12 hours)
-
broad-spectrum
antibiotics (eg, ciprofloxacin 400 mg every 12 hours
and metronidazole 500 mg every eight hours).
-
When fail to improve
by the third day of intensive treatment è cyclosporine or infliximab or undergo colectomy.
-
Cyclosporine: Intravenous as a short-term
"bridge" to therapy with the slower onset, longer acting medications,
including azathioprine (AZA) or 6-mercaptopurine (6-MP).
-
Infliximab: can induce remission rapidly and can be used
for the maintenance of remission. For patients with an allergy to AZA/6-MP or who have failed to AZA/6-MP.
-
Colectomy: When Patients with fulminant colitis
fail treatment with cyclosporine or infliximab within four
to seven days and those with toxic megacolon who do not respond to therapy within
72 hours.
Prognosis
-
Relapse in 10 years after
diagnosis: 67 %
-
Extension of colonic
disease is seen in up to 20 % of patients within five years.
-
Approximately 20 to 30 % of
patients with ulcerative colitis will require colectomy for acute complications
or for medically intractable disease.
-
Poor
prognostic factors in ulcerative colitis.
![]() |
Source: ACG Clinical Guideline: Ulcerative Colitis in Adults |
Complications
- Severe bleeding:
in up to 10% of Patients
- Fulminant
colitis and toxic megacolon:
Fulminant colitis: is
defined as:
-
>10 stools per day
-
continuous bleeding
-
abdominal pain, distension
-
acute, severe toxic
symptoms including fever and anorexia.
Toxic megacolon: is characterized by:
-
colonic diameter ≥6 cm or
cecal diameter >9 cm
·
The presence of systemic
toxicity (fever (temperature ≥37.5ºC), tachycardia (HR
≥90 beats/minute), anemia (hemoglobin <10.5 g/dL), or an
elevated ESR (≥30 mm/hour).
·
Perforation:
Perforation of the colon most commonly occurs as a consequence of
toxic megacolon but may also occurs without megacolon. Mortality by perforation
with consequent peritonitis up to 50%.
- Stricture:
Benign strictures can occur due to repeated episodes of
inflammation and muscle hypertrophy in about 10 % of cases with ulcerative
colitis
- Dysplasia or
colorectal cancer:
the cumulative incidence of CRC was 2.5 % after
20 years and 7.6 % after 30 years of disease
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