Download Ulcerative colitis

Ulcerative colitis
Disease distribution
Ulcerative Colitis
Left sided
cloitis
Proctitis
Proctosigmoiditis
Disease distribution
• The disease typically is most severe distally and
progressively less severe more proximally.
• In contrast to Crohn's disease, continuous and
symmetrical involvement is the hallmark of UC,
with sharp transition between diseased and
uninvolved segments of bowel
Clinical Features
diarrhea
tenesmus
rectal
bleeding
passage of
mucus
urgency
abdominal
pain
Systemic manifestations
Fever
Weight loss
Peripheral edema
Anorexia/vomiting
Clinical Features
The onset of UC typically is slow and insidious.
Symptoms have usually been present for weeks or months by the time the
patient seeks medical attention.
The median interval between the onset of symptoms and diagnosis of UC is
approximately 9 months.
Some patients with UC may present much more acutely, with symptoms
mimicking infectious colitis.
Physical findings
• mild or even moderately severe disease:
- few abnormal physical signs
• severe attacks :
-tachycardia
-fever
-orthostasis
-weight loss
• fulminant colitis:
- the abdomen often becomes distended and
firm, with absent bowel sounds and signs of
peritoneal inflammation.
Laboratory Findings
Laboratory findings in UC are nonspecific and reflect the severity of the underlying disease
Patients with active proctitis and proctosigmoiditis often have normal laboratory test results
Anemia, leukocytosis and thrombocytosis, reflect active disease.
Serum inflammatory markers including erythrocyte sedimentation rate (ESR) and C-reactive
protein (CRP) may be elevated in active disease.
Elevation in these inflammatory parameters is neither sensitive nor specific for UC; however,
measuring them may be useful in clinical practice to assess disease activity in individual
patients, particularly if these values are normal during periods of inactive disease.
Laboratory findings
Hypokalemia, metabolic alkalosis, and elevated serum creatinine may be present in severe
flares of UC
Hypoalbuminemia may be seen with both acute and chronic disease.
Minor elevations in serum levels of aspartate aminotransferase or alkaline phosphatase also are
frequently associated with severe disease, but these changes are transient and return to
normal when the disease enters into remission. These abnormalities probably reflect a
combination of fatty liver, sepsis, and poor nutrition.
Persistently elevated liver biochemical tests, especially serum alkaline phosphatase, are seen in
about 3% of patients with UC and should lead to further investigation, particularly to exclude
the presence of primary sclerosing cholangitis (PSC)
Natural history & Prognosis
80% of patients with UC have a disease course characterized by
intermittent flares interposed between variable periods of
remission.
The duration of relapse-free periods varies greatly from patient to
patient.
> 50% of patients present with mild disease at their first attack
6% to 19% of patients have severe disease at presentation.
Natural history & Prognosis
Following the initial flare, 40% to 65% of patients have an intermittent course, and 5% to
10% of patients have a chronic continuous course.
Up to 10% of patients have a severe first attack ultimately requiring colectomy.
Twenty-five years after the diagnosis of UC, 90% of patients still have a relapsing course
The probability of remaining in remission for 1 year after a relapse has been estimated at
30%.
After being in remission for 1 year, the risk of relapse decreases to 20% for the following
year.
Few patients (1%) diagnosed with UC have only one attack followed by a relapse-free
course, and they likely represent misdiagnosed infectious colitis.
Natural history & Prognosis
Disease extent may progress over time.
In patients initially presenting with proctitis or
proctosigmoiditis, disease extension occurs in approximately
10% to 30% of patients at 10 years after diagnosis.
Less commonly, extensive colitis regresses over time with
treatment
Colectomy in Ulcerative colitis
• The probability of colectomy is highest in the first
year of diagnosis
• the overall colectomy rate is 24% at 10 years and
30% at 25 years
• The probability of colectomy is related to the
extent of disease at diagnosis.
Exacerbating factors
bacterial and viral
infections
psychosocial stress.
seasonality
the use of nonsteroidal antiinflammatory drugs
(NSAIDs) antibiotics
smoking
Diagnosis
• No single test allows the diagnosis of UC with
acceptable sensitivity and specificity.
• the diagnosis relies on a combination of :
-compatible clinical features
-endoscopic appearances
-histologic findings.
• Stool cultures should be obtained to exclude
infectious colitis
Diagnosis
• colonoscopy should be performed to establish the
extent of the disease and to exclude Crohn's
disease.
• Multiple biopsy specimens should be taken from
throughout the colon to map the histologic extent
of disease and to confirm the diagnosis if there is
concern about Crohn's disease.
• Additionally, intubation and biopsy of the terminal
ileum should be attempted to exclude the presence
of Crohn's disease.
Endoscopic findings
The hallmark of UC is symmetrical
and continuous inflammation that
begins in the rectum and extends
proximally without interruption for
the entire extent of disease.
Endoscopic findings
The earliest endoscopic sign of UC is a decrease or loss of the normal
vascular pattern, with erythema and edema of the mucosa
As the disease progresses, the mucosa becomes granular and friable
With more severe inflammation, the mucosa may be covered by yellowbrown mucopurulent exudates associated with mucosal ulcerations.
severe UC is associated with mucosa that bleeds spontaneously, and there may
be extensive areas of denuded mucosa from severe mucosal ulcerations with
diffuse colitis. Marked edema may at times lead to luminal narrowing.
ENDOSCOPIC SPECTRUM OF SEVERITY
Endoscopic findings
In patients with long-standing UC, pseudopolyps may be present.
Inflammatory pseudopolyps develop in active disease and result from inflamed,
regenerating epithelium that is interposed among ulcerations.
These inflammatory pseudopolyps give the colonic mucosa a cobblestone appearance.
With repeated inflammation that is followed by healing, these pseudopolyps remain
during quiescent disease and usually do not regress with treatment.
Endoscopically, pseudopolyps typically are small, soft, pale, fleshy, and glistening;
however, they may be large, sessile, or pedunculated and may have surface ulcerations.
Differentiation of these benign pseudopolyps from neo-plastic polyps may be difficult and
requires histologic confirmation.
Endoscopic findings
• Strictures occasionally may be present in patients
with chronic UC
• Caused by focal muscular hypertrophy associated
with inflammation.
• Malignancy must be excluded in patients with UC
who have strictures, particularly those with long
strictures without associated inflammation and
those proximal to the splenic flexure.
Radiology: Barium enema
• less frequently used in the care of patients
with UC
• may be superior to colonoscopy for certain
indications
Stricture
Location
Length
Diameter
Radiology: Plain film of the abdomen
Patients with a severe attack of UC
should have a supine plain film of the
abdomen
The presence of marked colonic
dilatation suggests fulminant colitis
or toxic megacolon
Assessment of disease severity
• Mild
<4 stools/day, without or with only small amounts of
mucus
No blood
No fever
No tachycardia
Mild anemia
ESR < 30 mm/hr
• Moderate
Intermediate between mild and severe
• Severe
>6 stools/day, with blood
Fever > 37.5°C
Heart rate > 90 beats/min
Anemia with hemoglobin < 75% of normal
Mayo score
• A numerical disease activity instrument
• It is the sum of scores from four components
stool frequency
rectal bleeding
sigmoidoscopic
findings
physician's
global
assessment.
• It ranges from 0 to 12, with the higher total score
indicating a more severe disease
Mayo score
Variable
Score
Variable
0
Normal
Mucosal
Appearance
1
1-2 stools/day > normal
2
3-4 stools/day > normal
3
>4 stools/day > normal
Stool frequency
Rectal Bleeding
0
None
1
Streaks of blood
2
Obvious blood
3
Mostly blood
Score
0
Normal
1
Mild friability
2
Moderate friability
3
Exudation,
spontaneous bleeding
Physician Global
Assessment
0
Normal
1
Mild
2
Moderate
3
Severe
Mayo score
• Remission: score <2
• severe disease: score> 10
• Clinical response: decrease by 3 points from
the patient's initial baseline score.
Fulminant colitis
• Patients with severe fulminant colitis:
- appear toxic
-fever higher than 101°F
-tachycardia
- abdominal distention
-signs of localized or generalized peritonitis
-leukocytosis
• Toxic megacolon: radiologic evidence of colon
dilatation to greater than 6 cm in an acutely ill patient.
• Fulminant colitis and toxic megacolon are clinical
diagnoses, and endoscopic examination should be
avoided in patients with severe or fulminant colitis
because of the risk of inducing megacolon or
perforation.
Differentiating crohn’s disease from
ulcerative colitis
Variable
Crohn’s disease
Ulcerative colitis
Distribution
Often discontinuous and asymmetric
with skipped segments and normal
intervening mucosa, especially in
early disease
Continuous, symmetric, and diffuse,
with granularity or ulceration found
throughout the involved segments of
colon; periappendiceal inflammation
(cecal patch) is common even when
the cecum is not involved
Rectum
Completely, or relatively, spared
Typically involves the rectum with
proximal involvement to a variable
extent
Ileum
Often involved (≈75% of cases of
Crohn's disease
Not involved, except as “backwash”
ileitis in ulcerative pancolitis
Depth of
inflammation
Submucosal, mucosal, and
transmural
Mucosal; not transmural except in
fulminant disease
Differentiating crohn’s disease from
ulcerative colitis
Variable
Crohn’s disease
Ulcerative colitis
Strictures
Often present
Rarely present; suggestive of
adenocarcinoma
Fistulas
Perianal, enterocutaneous,
rectovaginal, enterovesicular, and
other fistulas may be present
Not present, except rarely for
rectovaginal fistula
Granulomas
Present in 15-60% of patients
(higher frequency in surgical
specimens than in mucosal pinch
biopsies)
Generally not present
Serology
pANCA positive in 20-25%; ASCA
positive in 41-76%
pANCA positive in 60-65%; ASCA positive
in 5%
Extraintestinal manifestations of IBD
Extraintestinal manifestations
• numerous complications may occur distant from the bowel
• Many of these complications are common to both Crohn's
disease and ulcerative colitis
• In large series, extraintestinal manifestations are found to
occur more frequently in Crohn's disease than in ulcerative
colitis and are more common among patients with colonic
involvement than in patients with no colonic inflammation
• one fourth of all patients with Crohn's disease will have an
extraintestinal manifestation of IBD.
Extraintestinal manifestations of IBD
Extraintestinal
manifestations
Related to
disease activity
Unrelated to
colitis
Musculoskeletal Manifestations
• Among the most common extraintestinal
manifestations are disorders of the bones and
joints
• In most patients, joint symptoms occurred in
the setting of a relapse of bowel symptoms
• Among patients with Crohn's disease, nearly
one half had joint symptoms in association
with a relapse in bowel disease.
Musculoskeletal Manifestations
Type 1
Peripheral
Type 2
Arthropathy
Sacroilitis
Axial
Spondylitis
Peripheral arthropathy
Features
Number of joints affected
Type1
Type2
<5
>5
Joints affected
Mainly large joints
Joints affected
Asymmetrical
Symmetrical
Parallel
Independent
<10 wk (median 5 wk)
Months to years (median 3 yr)
Association with bowel
disease activity
Duration of attacks
Mainly small joints
Musculoskeletal Manifestations
• Axial arthropathy occurs less frequently than
does peripheral arthropathy in patients with
IBD, and includes sacroiliitis and spondylitis.
• Spondylitis associated with IBD presents as
insidious low back pain and morning stiffness
that is improved by exercise.
• Does not parallel the activity of bowel disease
Skin: pyoderma gangrenosum
• The most common skin lesions associated
with IBD are pyoderma gangrenosum and
erythema nodosum.
• Neither condition is found solely in IBD, and
the finding of one or the other lesion is not
specific for either major form of IBD.
Skin: pyoderma gangrenosum
• Pyoderma gangrenosum appears first as a papule,
pustule, or nodule and progresses to an ulcer with
undermined borders. The ulcer typically has a
violaceous rim and crater-like holes pitting the base
• most often appears on the leg however it can occur
virtually anywhere on the body.
• Rare, occurs in 1-2% of patients
• In Crohn's disease pyoderma gangrenosum often
occurs without an associated flare of bowel
symptoms.
Skin: pyoderma gangrenosum
Skin: erythema nodosum
The classic appearance is of tender subcutaneous nodules with an erythematous or dusky
appearance, most often seen on the pretibial region.
erythema nodosum is much more frequently seen in women than in men, occurs in 2% to 4%
of patients with UC
often presents during exacerbations of bowel disease and tends to improve with treatment of
the underlying bowel disease. Severe or refractory cases may require systemic glucocorticoids
or immunosuppressive therapy.
There is a strong association with arthropathy
If possible, erythema nodosum lesions should not be biopsied because biopsied lesions tend
to scar, whereas spontaneously resolving lesions heal without scar formation.
Erythema nodosum
Mucocutaneous Manifestations
• Aphthous ulcers of the mouth are common
among patients with Crohn's disease and
ulcerative colitis
• These lesions usually occur with flares of colitis
and resolve on control of the bowel disease
• Angular cheilitis is seen in nearly 8% of patients
with Crohn's disease.
• Angular stomatitis and a sore tongue may be
seen in patients with deficiencies of iron or other
micronutrients
Ocular Manifestations:episcleritis
• estimated to occur in 6% of patients with Crohn's
disease, 5% of patients with ulcerative colits
• consists of painless hyperemia of the sclera and
conjunctiva with no affection of visual acuity.
• It typically parallels the activity of bowel disease
and usually responds to anti-inflammatory
therapy
Ocular Manifestations: uveitis
• uveitis presents as an acute or subacute painful
eye with visual blurring and often photophobia
and headache. Visual acuity is preserved unless
the posterior segment becomes involved.
• Temporal correlation of uveitis with the activity of
the colitis is less predictable than with
episcleritis.
• Uveitis should receive prompt treatment with
local steroid ocular drops to prevent progression
to blindness.
Hepatobiliary Manifestations
• Gallstones are found in more than 25% of men and women
with Crohn's disease, representing a relative risk of 1.8
compared with the general population.
• Asymptomatic and mild elevations of liver biochemical tests
often are seen in IBD. In most cases, the levels return to
normal once remission is achieved. These abnormalities are
thought to be related to a combination of factors, including
malnutrition, sepsis, and fatty liver.
• Primary sclerosing cholangitis more often is associated with
ulcerative colitis but may occur in 4% of patients with Crohn's
disease, usually those with colonic involvement.
Hepatobiliary Manifestations :PSC
• PSC should be excluded in patients with UC who
have persistently abnormal liver tests or evidence of
chronic liver disease.
• PSC is independent of the underlying colitis and it
usually follows a progressive course after many
years of stable disease.
• Unfortunately, no treatment has been shown
definitively to be effective.
Renal and Genitourinary Manifestations
• uric acid and oxalate stones are common in patients
with Crohn's disease. In the setting of fat
malabsorption resulting from intestinal resection or
extensive small bowel disease, luminal calcium binds
free fatty acids, thereby decreasing the calcium that is
available to bind and clear oxalate. Increased oxalate is
absorbed as the sodium salt, resulting in hyperoxaluria
and calcium oxalate stone formation.
• Uric acid stones are believed to result from volume
depletion and a hypermetabolic state.
• More rare complications include membranous
nephropathy, glomerulonephritis, and renal
amyloidosis..
Coagulation and Vascular Complications
• The occurrence of hypercoagulability is a well-recognized
complication of IBD.
• Patients may present with venous thromboembolism or, much
less commonly, arterial thrombosis.
• The hypercoagulable state is multifactorial.
• A variety of coagulation and platelet abnormalities may be
present in patients with UC, particularly those with severe
disease, and include:
- thrombocytosis
- increased levels of fibrinogen, coagulation factors V and VIII
and plasminogen activator inhibitor
-decreased levels of antithrombin III, proteins C and S, factor V
Leiden, and tissue plasminogen activator.
Serological markers in IBD
• CRP
• P-ANCA
• ASCA
Serological markers in IBD
• May be useful in predicting the phenotype of
crohn’s disease
• There are association between ASCA and
Small bowel
diseae
Fibrostenotic
disease
Perforation
Small bowel
surgery
Serological markers in IBD
• Patient with positive serology and high titer
are more likely to have complications:
strictures
surgery
requirements
perforating
disease