//fpnotebook.com/
Ulcerative Colitis
Aka: Ulcerative Colitis, Idiopathic Proctocolitis
- See Also
- Crohn's Disease
- Inflammatory Bowel Disease
- Definitions
- Ulcerative Colitis
- Inflammatory Bowel Disease affecting the mucosa of the Large Intestine and Rectum
- Presents with Abdominal Pain, bloody Diarrhea, fever and weight loss
- Epidemiology
- Most common cause of chronic colitis
- Incidence: 2-7 cases per 100,000 per year in U.S.
- Prevalence: 250,000 to 500,00 persons affected in United States
- More common in industrialized countries
- Onset
- First peak onset at age 15 to 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 Bacterial Gastroenteritis infections are associated with 10 fold risk of Ulcerative Colitis development
- Nontyphoid Salmonella
- Campylobacter
- Clostridioides difficile
- Genetic 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 and soda intake
- Higher risk with increased meat and fat intake
- Decreased risk with increased vegetable intake
- Decreased with tea intake
- Decreased in infants who were Breast fed
- 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: Presentations
- Typical presentation
- Hematochezia
- Diarrhea
- Abdominal Pain
- Classic Presentation
- Intermittent bloody Diarrhea
- Rectal or fecal urgency
- Tenesmus
- Symptoms: General
- Abdominal Pain
- Rectal Bleeding (Hematochezia)
- Helps to differentiate from Crohn's Disease
- Bloody Diarrhea is the most common presenting complaint
- Diarrhea
- Tenesmus
- Fever
- Malaise
- Weight loss
- Signs: Extraintestinal Manifestations
- Similar findings seen in Crohn's Disease
- However extraintestinal findings are more common with Crohn's Disease
- Musculoskeletal
- Osteoporosis (15%)
- Colitic Arthritis or Arthralgias (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 Ulcers or Canker Sores (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 or NAAT
- Stool for Ova and Parasites
- Clostridium difficile Toxin and culture
- Labs: Markers of inflammation and malabsorption
- Fecal Calprotectin (see below)
- Useful in both diagnosis and in predicting relapse versus remission
- 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
- Complete Blood Count
- Hemoglobin or Hematocrit decreased in moderate to severe cases
- Labs: Diagnosis
- Fecal Calprotectin
- No serum biomarker completely excludes diagnosis in ongoing symptoms, or in adults
- Normal Fecal Calprotectin <100 mcg/g in CHILDREN nearly excludes Ulcerative Colitis
- Walker (2020) Arch Dis Child 105(10): 957-63 [PubMed]
- 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
- Lactoferrin
- Diagnosis: Colonoscopy
- Indications
- Colonoscopy should be performed in all patients suspected of Ulcerative Colitis
- Colonoscopy is the gold standard for Ulcerative Colitis diagnosis
- Distribution
- Mucosal inflammation begins at Rectum
- Inflammation extends without interruption
- Inflammation ends in a distinct proximal margin
- Regions
- Proctitis (anal verge to 18 cm proximally)
- Left-sided Colitis (anal verge to splenic flexure)
- Pancolitis (anal verge to regions proximal to the splenic flexure)
- 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
- Radiation Colitis
- Diverticulitis
- Infectious Colitis
- Amebic Dysentery
- Travel history to endemic regions
- Clostridium difficile infection
- Bacterial Acute Inflammatory Diarrhea (e.g. Salmonella, Shigella, E. coli, Yersinia, Campylobacter)
- Parasitic colitis
- Viral colitis
- Cytomegalovirus (CMV) in Immunocompromised patients
- Grading: Severity
- Mild Cases
- Stools: <4/day
- Bloody stool: Variable
- ESR or CRP: Normal (as are other lab and exam findings - see below)
- Systemic toxicity: Absent
- Moderate Cases
- Stools: 4-6/day
- Bloody stool: Variable
- ESR or CRP: Normal to elevated
- Systemic toxicity: Absent
- Severe Cases
- Stools: 7-10/day
- Bloody stool: Present
- ESR or CRP: Increased
- Systemic toxicity: Present
- Fever
- Tachycardia
- Leukocytosis
- Anemia
- Fulminant Cases
- Stools: >10/day
- Bloody stool: Present
- ESR or CRP: 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 Movements >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 Corticosteroids
- 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 Corticosteroids for 4-6 weeks
- If remission occurs, transition to biologic agents (see below) at maintenance dosing
- Step 3: Biologic Agents (see below)
- If remission occurs, continue biologic agent (see below) at maintenance dosing
- Severe to fulminant colitis
- Hospital admission (up to 25% of Ulcerative Colitis acute presentations)
- Step 1: Corticosteroids IV at active dose for 3-5 days
- If remission occurs, transition to biologic agents at maintenance dosing
- Step 2: Biologic agents are considered first-line therapy
- Consider Cyclosporine or Infliximab for failed response to Corticosteroids
- 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: 5-Aminosalicylic Acid Derivatives in Mild to Moderate disease
- Agents: 5-Aminosalicylic Acid Derivatives (5-ASA agents)
- No Sulfa Allergy: Sulfasalazine (Azulfidine)
- Often avoided in favor of non-sulfa 5-ASA agents
- Sulfasalazine is dosed four times daily, and is associated with Headache, Nausea, rash
- Mesalamine and other non-sulfa agents have higher efficacy in inducing remission
- 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: Corticosteroids for 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
- Corticosteroids: 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 Corticosteroids gradually to prevent rebound
- Continue starting dose until clinical response (typically 10-14 days)
- After response, reduce dose by 5mg per week
- Efficacy
- Systemic Corticosteroids do not maintain remission and have serious side effects
- Coticosteroids: Uceris (extended release Budesonide)
- Uceris (extended release Budesonide) 9 mg orally daily for up to 8 weeks
- Uceris cost is an 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 Corticosteroids with their multitude of adverse effects
- Uceris Systemic Corticosteroid effects are increased with CYP3A4 Inhibitors
- Criscuoli (2013) Gastroenterology 144(3):e23 [PubMed]
- Corticosteroids: 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: Biologic Agents and Immunosuppressants for Refractory Disease
- Indications
- Poor control with Corticosteroids
- Serious Corticosteroid complications
- Steroid dependent to control symptoms
- May avert surgical resection
- Interleukin Inhibitors (IL-12, IL-23)
- Ustekinumab (Stelera)
- Start: 260 to 520 mg injection (weight based)
- Next: 90 mg every 8 weeks
- Janus Kinase Inhibitors
- Tofacitinib (Xeljanz)
- Start: 10 mg orally twice daily for 8 weeks
- Next: 5 to 10 mg orally twice daily
- Selective Adhesion Molecule Inhibitors
- Vedolizumab (Entyvio)
- Start: 300 mg at week 0, 2 and 6
- Next: 300 mg every 8 weeks
- Tumor Necrosis Factor Inhibitors (TNF-alpha)
- Adalimumab (Humira)
- Start: 160 mg at week 0
- Next: 80 mg at week 2
- Next: 40 mg every other week
- Golimumab (Simponi)
- Start: 200 mg at week 0
- Next: 100 mg at week 2
- Next: 100 mg every 4 weeks
- Infliximab (Remicade)
- Active Disease: 5-10 mg/kg on weeks 0, 2 and 6
- Maintenance: 5-10 mg/kg every 4-8 weeks
- Older Agents
- 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 Corticosteroids
- Maintenance: Not indicated
- 6-Mercaptopurine (Purinethol)
- Duration
- For long term therapy only
- Ineffective for acute dx
- Onset of action: 2-6 months
- Complications
- Bancruptcy (most of these agents are >$5000 per month)
- Pancreatitis
- Infection risk
- Hepatitis
- Bone Marrow suppression (Follow Complete Blood Count)
- Management: Surgery
- Surgical management of Ulcerative Colitis is curative
- Colectomy Prevalence 15% in Ulcerative Colitis
- Indications
- Medical failure (e.g. 3 days of IV Corticosteroids)
- 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
- Increased risk of Bowel Obstruction
- Pouchitis (50%)
- Postoperative, autoimmune inflammation of residual rectal tissue
- 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
- General 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%
- Fecal Calprotectin elevation predicts relapse (while negative serial values predict remission)
- Heida (2017) Inflamm Bowel Dis 23(6): 894-902 [PubMed]
- Remission for 15 years: 10%
- Mortality within 1 year of initial attack was previously estimated at 5%
- Later studies show no increased mortality
- Fumery (2018) Clin Gastroenterol Hepatol 16(3): 343-56 [PubMed]
- Undergo total proctocolectomy within 5 years: 25%
- Prognosis: Predictors of Aggressive Disease
- Age <40 years old
- Pancolitis
- Severe disease on endoscopy
- Extraintestinal manifestations
- Increased inflammatory markers
- Early need for Corticosteroids
- Prevention: Probiotics, Herbals, General Measures for maintenance of remission
- Probiotics
- VSL #3
- Probiotic that improves symptoms and reduces pouchitis
- Tursi (2010) Am J Gastroenterol 105(10):2218-27 [PubMed]
- Lactobacillus GG
- Zocco (2006) Aliment Pharmacol Ther 23(11): 1567-74 [PubMed]
- ProbioticE. coli Nissle 1917
- As effective as Mesalamine in relapse prevention
- Kruis (2004) Gut 53:1617-23 [PubMed]
- Lifestyle
- Regular Exercise
- Eckert (2019) BMC Gastroenterol 19(1): 115 [PubMed]
- Avoid FODMAPS
- Avoid NSAIDs, Opioids and Anticholinergic Agents during acute exacerbations as musch as possible
- Other medications
- Curcumin
- Dosed 2 to 3 g daily, adjunctive in mild Ulcerative Colitis
- Coeiho (2020) Nutrients 12(8): 2296 [PubMed]
- Complication Evaluation and prevention
- Periodic DEXA Scan (esp. with regular Corticosteroid)
- Vaccination (manage as Immunocompromised state)
- Skin cancer screening
- Annual Cervical Cytology (Pap Smear)
- See Colon Cancer screening above
- References
- (2019) presc Lett 16(4): 22
- Adams (2013) Am Fam Physician 87(10): 699-705 [PubMed]
- Adams (2022) Am Fam Physician 105(4): 406-11 [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]