IBD
Ulcerative Colitis
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Ulcerative Colitis
Epidemiology
Most common cause of chronic colitis
Incidence
: 2-7 cases per 100,000 per year
Prevalence
: 250,000 to 500,00 persons affected in United States
Onset
First peak onset at age 15-25 years (up to age 40 years)
Second peak onset occurs after age 50 years
Gender: Men and women affected equally
Risk Factors
Less common in ongoing
Tobacco Abuse
but risk is higher after
Tobacco Cessation
Boyko (1987) N Engl J Med 316:707-10 [PubMed]
Specific
Bacteria
l
Gastroenteritis
infections are associated with 10 fold risk of Ulcerative Colitis development
Nontyphoid
Salmonella
Campylobacter
Gene
tic predisposition
Family History
confers 10 fold risk
Ashkenazi Jewish population afflicted more often
Siblings with disease increase risk
Sibling: 4.6 fold increased risk
Monozygotic twin: 95 fold increased risk
Dietary factors
Higher risk with refined sugar intake
Higher risk with increased meat and fat intake
Decreased risk with increased vegetable intake
Pathophysiology
Etiology unknown
Inflammation localized to mucosa only
Crohn's Disease
involves all layers of bowel wall
Always involves
Rectum
and extends proximally to contiguous sections of colon
Ulcerative
Proctitis
Involves Distal 12 cm colonic mucosa
Proctosigmoiditis
Involves
Rectum
to splenic flexure
Pancolitis
Involves
Rectum
to cecum
Symptoms
Typical presentation
Hematochezia
Diarrhea
Abdominal Pain
Classic Presentation
Intermittent bloody
Diarrhea
Rectal urgency
Tenesmus
Symptoms
Gene
ral
Abdominal Pain
Rectal Bleeding
(
Hematochezia
)
Helps to differentiate from
Crohn's Disease
Diarrhea
Tenesmus
Fever
Malaise
Weight loss
Signs
Extraintestinal Manifestations
Similar findings seen in
Crohn's Disease
Musculoskeletal
Osteoporosis
(15%)
Colitic Arthritis
or
Arthralgia
s (5-21% of cases)
Ankylosing Spondylitis
(2%)
Ocular
Episcleritis
(parallels Ulcerative Colitis course)
Uveitis
(occurs in up to 3-4% of cases)
Variable course
Associated with
Enteropathic Arthritis
Recurrent
Iritis
Dermatologic
Digital Clubbing
(presence increases likelihood of Ulcerative Colitis)
Erythema Nodosum
(3%)
Parallels Ulcerative Colitis course
Pyoderma Gangrenosum
(up to 2% of cases)
Lichen Planus
Aphthous Stomatitis
,
Aphthous Ulcer
s or
Canker Sore
s (4%)
Psoriasis
(1%)
Hepatobiliary
Hepatic
Steatosis
Primary Sclerosing Cholangitis
(4-5% co-
Incidence
)
Cholelithiasis
Pericholangitis
Miscellaneous
Nephrolithiasis
Hypercoagulable
state
Deep Vein Thrombosis
or
Pulmonary Embolism
in 0.3% of cases
Labs
Distinguish from infectious causes of colitis
Stool Culture
Stool
for
Ova and Parasite
s
Clostridium difficile Toxin
and culture
Labs
Markers of inflammation and malabsorption
C-Reactive Protein
(
C-RP
) or
Erythrocyte Sedimentation Rate
(ESR)
Mildly increased in moderate to severe cases
Electrolyte
abnormalities related to
Chronic Diarrhea
(e.g.
Hypokalemia
)
Serum Albumin
Decreased in moderate to severe cases
Hemoglobin
or
Hematocrit
Decreased in moderate to severe cases
Labs
Diagnosis
Biopsy of colon wall (via
Colonoscopy
as described below)
Diffuse, shallow, mucosa ulceration
Crypt abscess and branching
Muscularis mucosal thickening
Inflammatory cell infiltration
Labs
Experimental markers
pANCA with ASCA
Combination is sensitive but not specific (pending further study)
Labs
Perinuclear antineutrophilic cytoplasmic antibodies (pANCA) and
Anti-Saccharomyces cerevisiae antibodies (ASCA)
References
Reese (2006) Am J Gastroenterol 101:2410-22 [PubMed]
Other markers increased in Ulcerative Colitis
Fecal Calprotectin
Lactoferrin
Diagnosis
Colonoscopy
Findings (gold standard for diagnosis)
Gene
ral
Mucosal inflammation begins at
Rectum
Inflammation extends without interruption
Inflammation ends in a distinct proximal margin
Mild disease
Erythematous mucosa
Decreased vascular pattern visualization
Fine mucosal friability
Moderate disease
Diffuse edema and erythema
Loss of vascular pattern
Superficial erosions
Mucosa bleeds with minimal
Trauma
Severe disease
Frank Ulceration
Spontaneous bleeding
Imaging
Not recommended for diagnosis unless endoscopy not available
Double contrast
Barium Enema
and
Small Bowel
follow-through
Haustra loss
Contiguous inflammation from
Rectum
proximally
Contrast with non-contiguous and
Small Bowel
lesions of
Crohn's Disease
Abdominal XRay (long-standing disease signs)
Bowel
shortening
Haustra loss
Lumen narrowing and rigid appearance
Differential Diagnosis
See
Inflammatory Bowel Disease
Crohn's Disease
Ischemic Colitis
Microscopic Colitis
Diverticulitis
Infectious Colitis
Amebic dysentary
Clostridium difficile
infection
Bacteria
l colitis
Parasitic colitis
Viral colitis
Grading
Severity
Mild Cases
Stool
s: <4/day
Bloody stool: Variable
ESR: Normal (as are other lab and exam findings - see below)
Systemic toxicity: Absent
Moderate Cases
Stool
s: 4-6/day
Bloody stool: Variable
ESR: Normal to elevated
Systemic toxicity: Absent
Severe Cases
Stool
s: 7-10/day
Bloody stool: Present
ESR: Increased
Systemic toxicity: Present
Fever
Tachycardia
Leukocytosis
Anemia
Fulminant Cases
Stool
s: >10/day
Bloody stool: Present
ESR: Increased
Systemic toxicity: Present
Severe symptoms above AND
Abdominal tenderness or distention
Continuous bleeding needing transfusion
Grading
Lab and Exam based
Moderate to severe criteria
Serum Albumin
<3.5 mg/dl (Severe: <3.0 mg/dl)
Body Temperature
>99 F or 37.2 C (Severe: >100 F or 37.8 C)
Bowel Movement
s >4 per day (Severe: >6 per day)
ESR >20 mm/hour (Severe: >30 mm/hour)
Hematocrit
<40% (Severe: <30%)
Heart Rate
>90 beats per minute (Severe: >100 beats per minute)
Weight loss >1% (Severe: >10%)
References
Chang (2004) Gastroenterol Clin North Am 33:236 [PubMed]
Management
Approach
Mild to moderate distal colitis
When remission occurs with any step, transition to maintenance dosing of current agent
Step 1: Topical
5-ASA
at active dose per
Rectum
for 4-6 weeks
Suppository for isolated
Proctitis
Enema for more proximal, left-sided Ulcerative Colitis
Step 2: Consider ADDing shortterm rectal
Corticosteroid
s
Hydrocortisone
enema (Cortenema) or if enema not retained, then foam (Cortifoam, Uceris)
Step 3: ADD oral
5-ASA
at active dose for 4-6 weeks (while continuing rectal
5-ASA
)
Step 4: Go to step 2 under mild-moderate extensive colitis
Mild to moderate extensive colitis
Step 1: Oral
5-ASA
at active dose for 4-6 weeks
If remission occurs, continue oral
5-ASA
at maintenance dosing
Step 2: Oral
Corticosteroid
s for 4-6 weeks
If remission occurs, transition to
Azathioprine
(
Imuran
) at maintenance dosing
Step 3:
Infliximab
(
Remicade
) for 4-6 weeks
If remission occurs, continue
Infliximab
at maintenance dosing
Step 4: Consider third-line medications
Intravenous
Corticosteroid
s
Cyclosporine
(
Sandimmune
)
Step 5: Consider surgical intervention
See Colectomy below
Severe to fulminant colitis
Hospital admission
Step 1:
Corticosteroid
s IV at active dose for 3-5 days
If remission occurs, transition to
Azathioprine
(
Imuran
) at maintenance dosing
Step 2: Consider third-line medications
Cyclosporine
(
Sandimmune
) for 3-5 days
If remission occurs, transition to
Azathioprine
(
Imuran
) at maintenance dosing
Infliximab
(
Remicade
) for 3-5 days
If remission occurs, continue
Infliximab
at maintenance dosing
Step 3: Consider surgical intervention
See Colectomy below
References
Adams (2013) Am Fam Physician 87(10): 699-705 [PubMed]
Kornbluth (2010) Am J Gastroenterol 105(3): 501-23 [PubMed]
Management
Mild to Moderate disease
Agents:
5-Aminosalicylic Acid Derivative
s (
5-ASA
agents)
No
Sulfa Allergy
:
Sulfasalazine
(
Azulfidine
)
Often avoided in favor of
5-ASA
agents
Sulfasalazine
is dosed four times daily, and is associated with
Headache
,
Nausea
, rash
Active disease:
Sulfasalazine
4-6 grams/day divided four times daily
Maintenanance:
Sulfasalazine
2-4 grams/day divided four times daily
Sulfa Allergy
: 5-Aminosalicylic acid (
5-ASA
,
Mesalamine
,
Asacol
,
Pentasa
)
Oral (
Asacol
)
Active disease: 2.4 to 4.8 grams/day divided 3 times daily
Maintenance: 1.2 to 2.4 grams/day divided 3 times daily
Suppository (Canasa)
Active disease: 1000 mg once daily
Maintenance: 500 mg once to twice daily
Enema (
Rowasa
)
Active disease: 1 to 4 grams daily
Maintenance: 2-4 grams daily to every third day
Other
5-ASA
agents
Olsalazine (Dipentum) 500 mg PO bid
Lialda
(
Mesalamine
) once daily
Balsalazide (Colazal,
Mesalamine
) dosed three times daily
Duration of medication use: 6-12 weeks
Taper preparations to prevent rebound
Route
Rectal suppositories are preferred for
Proctitis
Use oral and rectal agents together for pancolitis
Combined oral and rectal agents are more effective than either one alone
Management
Moderate to Severe disease
Precaution
Use only to stabilize active Ulcerative Colitis
Avoid chronic use as these do not maintain remission and have serious longterm adverse effects
Corticosteroid
s: Systemic
Agents
Prednisone
40-60 mg/day orally until improving, then decrease daily dose by 5-10 mg each week
Methylprednisolone
(Medrol) 40-60 mg/day orally
Hydrocortisone
(Cortef) 200-300 mg/day orally
Methylprednisolone
(Solu-Medrol) 40 mg IV daily
Taper
Corticosteroid
s gradually to prevent rebound
Continue starting dose until clinical response (typically 10-14 days)
After response, reduce dose by 5mg per week
Efficacy
Systemic Corticosteroid
s do not maintain remission and have serious side effects
Coticosteroids: Uceris
Uceris is a very expensive ($1200/month) oral budesonide tablet that primarily works locally in colon
Contrast with Entocort EC that targets ileum and ascending colon in
Crohn's Disease
Contrast with
Systemic Corticosteroid
s with their multitude of adverse effects
Uceris
Systemic Corticosteroid
effects are increased with
CYP3A4
Inhibitors
Criscuoli (2013) Gastroenterology 144(3):e23 [PubMed]
Corticosteroid
s: Rectal (for distal Ulcerative Colitis)
Hydrocortisone
Enema (Cortenema) 100 mg daily to twice daily
Hydrocortisone
Acetate 10% rectal foam (Cortifoam) 90 mg once to twice daily
Disposition
Hospitalization required when cases refractory to oral steroids and possibly outpatient
Infliximab
trial or
Acute Abdomen
or systemic toxicity
Management
Immunosuppressants for Refractory disease
Indications:
Poor control with
Corticosteroid
s
Serious
Corticosteroid
complications
Steroid dependent to control symptoms
May avert surgical resection
Agents
Infliximab
(
Remicade
)
Active Disease: 5-10 mg/kg on weeks 0, 2 and 6
Maintenance: 5-10 mg/kg every 4-8 weeks
Azathioprine
(
Imuran
)
Active Disease: Not indicated
Maintenance: 50-100 mg/day
Cyclosporine
(
Sandimmune
)
Active Disease: 2-4 mg/kg/day
Consider in acute cases refractory to IV
Corticosteroid
s
Maintenance: Not indicated
6-Mercaptopurine (Purinethol)
Xeljanz
(
Tofacitinib
)
Oral
Monoclonal Antibody
available in 2019
Duration
For long term therapy only
Ineffective for acute dx
Onset of action: 2-6 months
Complications
Pancreatitis
Infection risk
Hepatitis
Bone Marrow
suppression (Follow
Complete Blood Count
)
Management
Surgery
Surgical management of Ulcerative Colitis is curative
Indications
Medical failure
Corticosteroid
intolerance
Growth retardation in children
Dysplasia or malignancy
Fulminant colitis with or without
Megacolon
Perforation
Peritonitis
Hemorrhage
Procedures
Total proctocolectomy (Brooke ileostomy)
Completely cures Ulcerative Colitis
Entire colorectal mucosa is excised
Results in gas or
Stool Incontinence
Requires external collecting bag
High rate of re-operation (>50%) due to post-surgical complication
Ileal pouch anal anastomosis
Patient maintains anal function and continence
Pouchitis occurs in 30-50% of patients
Complications
Colonic stricture and increased risk of
Bowel Obstruction
Pouchitis or Pouch dysfunction
References
Cima (2005) Arch Surg 140:300-10 [PubMed]
Complications
Colon Cancer
(Adenocarcinoma)
See monitoring below
Colon Cancer
risk is not increased in disease limited to
Proctitis
or proctosigmoiditis
Risk increases with duration since diagnosis
First 10 years: 2% risk
First 20 years: 8% risk
First 30 years: 18% risk
References
Eaden (2001) Gut 48:526-35 [PubMed]
Toxic
Megacolon
Bowel
Perforation
Colonic Stricture
Gastrointestinal Bleeding
Monitoring
Colon Cancer
Gene
ral
Colonoscopy
approach
Biopsies taken from cecum to
Rectum
every 10 cm
Pancolitis
Colonoscopy
every 1-2 years after 8-10 years of disease
Left-sided Colitis
Colonoscopy
every 3 years after 12-15 years of disease (British use 15-20 years)
Course
Following initial attack of Ulcerative Colitis
Continuous active Ulcerative Colitis: 75%
Remission for 15 years: 10%
Mortality within 1 year of initial attack: 5%
Undergo total proctocolectomy within 5 years: 25%
Prevention
Probiotic
s for maintenance of remission
Lactobacillus GG
Zocco (2006) Aliment Pharmacol Ther 23(11): 1567-74 [PubMed]
Probiotic
E. coli
Nissle 1917
As effective as
Mesalamine
in relapse prevention
Kruis (2004) Gut 53:1617-23 [PubMed]
References
(2019) presc Lett 16(4): 22
Adams (2013) Am Fam Physician 87(10): 699-705 [PubMed]
Carter (2004) Gut 53:V1-16 [PubMed]
Kornbluth (2004) Am J Gastroenterol 99:1371-85 [PubMed]
Kornbluth (2010) Am J Gastroenterol 105(3): 501-23 [PubMed]
Langan (2007) Am Fam Physician 76:1323-31 [PubMed]
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