II. Epidemiology

  1. Most common cause of chronic colitis
  2. Incidence: 2-7 cases per 100,000 per year
  3. Prevalence: 250,000 to 500,00 persons affected in United States
  4. Onset
    1. First peak onset at age 15-25 years (up to age 40 years)
    2. Second peak onset occurs after age 50 years
  5. Gender: Men and women affected equally

III. Risk Factors

  1. Less common in ongoing Tobacco Abuse but risk is higher after Tobacco Cessation
    1. Boyko (1987) N Engl J Med 316:707-10 [PubMed]
  2. Specific Bacterial Gastroenteritis infections are associated with 10 fold risk of Ulcerative Colitis development
    1. Nontyphoid Salmonella
    2. Campylobacter
  3. Genetic predisposition
    1. Family History confers 10 fold risk
      1. Ashkenazi Jewish population afflicted more often
    2. Siblings with disease increase risk
      1. Sibling: 4.6 fold increased risk
      2. Monozygotic twin: 95 fold increased risk
  4. Dietary factors
    1. Higher risk with refined sugar intake
    2. Higher risk with increased meat and fat intake
    3. Decreased risk with increased vegetable intake

IV. Pathophysiology

  1. Etiology unknown
  2. Inflammation localized to mucosa only
    1. Crohn's Disease involves all layers of bowel wall
  3. Always involves Rectum and extends proximally to contiguous sections of colon
    1. Ulcerative Proctitis
      1. Involves Distal 12 cm colonic mucosa
    2. Proctosigmoiditis
      1. Involves Rectum to splenic flexure
    3. Pancolitis
      1. Involves Rectum to cecum

V. Symptoms

  1. Typical presentation
    1. Hematochezia
    2. Diarrhea
    3. Abdominal Pain
  2. Classic Presentation
    1. Intermittent bloody Diarrhea
    2. Rectal urgency
    3. Tenesmus

VI. Symptoms: General

  1. Abdominal Pain
  2. Rectal Bleeding (Hematochezia)
    1. Helps to differentiate from Crohn's Disease
  3. Diarrhea
  4. Tenesmus
  5. Fever
  6. Malaise
  7. Weight loss

VII. Signs: Extraintestinal Manifestations

  1. Similar findings seen in Crohn's Disease
  2. Musculoskeletal
    1. Osteoporosis (15%)
    2. Colitic Arthritis or Arthralgias (5-21% of cases)
    3. Ankylosing Spondylitis (2%)
  3. Ocular
    1. Episcleritis (parallels Ulcerative Colitis course)
    2. Uveitis (occurs in up to 3-4% of cases)
      1. Variable course
      2. Associated with Enteropathic Arthritis
    3. Recurrent Iritis
  4. Dermatologic
    1. Digital Clubbing (presence increases likelihood of Ulcerative Colitis)
    2. Erythema Nodosum (3%)
      1. Parallels Ulcerative Colitis course
    3. Pyoderma Gangrenosum (up to 2% of cases)
    4. Lichen Planus
    5. Aphthous Stomatitis, Aphthous Ulcers or Canker Sores (4%)
    6. Psoriasis (1%)
  5. Hepatobiliary
    1. Hepatic Steatosis
    2. Primary Sclerosing Cholangitis (4-5% co-Incidence)
    3. Cholelithiasis
    4. Pericholangitis
  6. Miscellaneous
    1. Nephrolithiasis
    2. Hypercoagulable state
      1. Deep Vein Thrombosis or Pulmonary Embolism in 0.3% of cases

VIII. Labs: Distinguish from infectious causes of colitis

IX. Labs: Markers of inflammation and malabsorption

  1. C-Reactive Protein (C-RP) or Erythrocyte Sedimentation Rate (ESR)
    1. Mildly increased in moderate to severe cases
  2. Electrolyte abnormalities related to Chronic Diarrhea (e.g. Hypokalemia)
  3. Serum Albumin
    1. Decreased in moderate to severe cases
  4. Hemoglobin or Hematocrit
    1. Decreased in moderate to severe cases

X. Labs: Diagnosis

  1. Biopsy of colon wall (via Colonoscopy as described below)
    1. Diffuse, shallow, mucosa ulceration
    2. Crypt abscess and branching
    3. Muscularis mucosal thickening
    4. Inflammatory cell infiltration

XI. Labs: Experimental markers

  1. pANCA with ASCA
    1. Combination is sensitive but not specific (pending further study)
    2. Labs
      1. Perinuclear antineutrophilic cytoplasmic antibodies (pANCA) and
      2. Anti-Saccharomyces cerevisiae antibodies (ASCA)
    3. References
      1. Reese (2006) Am J Gastroenterol 101:2410-22 [PubMed]
  2. Other markers increased in Ulcerative Colitis
    1. Fecal Calprotectin
    2. Lactoferrin

XII. Diagnosis: Colonoscopy Findings (gold standard for diagnosis)

  1. General
    1. Mucosal inflammation begins at Rectum
    2. Inflammation extends without interruption
    3. Inflammation ends in a distinct proximal margin
  2. Mild disease
    1. Erythematous mucosa
    2. Decreased vascular pattern visualization
    3. Fine mucosal friability
  3. Moderate disease
    1. Diffuse edema and erythema
    2. Loss of vascular pattern
    3. Superficial erosions
    4. Mucosa bleeds with minimal Trauma
  4. Severe disease
    1. Frank Ulceration
    2. Spontaneous bleeding

XIII. Imaging

  1. Not recommended for diagnosis unless endoscopy not available
  2. Double contrast Barium Enema and Small Bowel follow-through
    1. Haustra loss
    2. Contiguous inflammation from Rectum proximally
      1. Contrast with non-contiguous and Small Bowel lesions of Crohn's Disease
  3. Abdominal XRay (long-standing disease signs)
    1. Bowel shortening
    2. Haustra loss
    3. Lumen narrowing and rigid appearance

XIV. Differential Diagnosis

XV. Grading: Severity

  1. Mild Cases
    1. Stools: <4/day
    2. Bloody stool: Variable
    3. ESR: Normal (as are other lab and exam findings - see below)
    4. Systemic toxicity: Absent
  2. Moderate Cases
    1. Stools: 4-6/day
    2. Bloody stool: Variable
    3. ESR: Normal to elevated
    4. Systemic toxicity: Absent
  3. Severe Cases
    1. Stools: 7-10/day
    2. Bloody stool: Present
    3. ESR: Increased
    4. Systemic toxicity: Present
      1. Fever
      2. Tachycardia
      3. Leukocytosis
      4. Anemia
  4. Fulminant Cases
    1. Stools: >10/day
    2. Bloody stool: Present
    3. ESR: Increased
    4. Systemic toxicity: Present
      1. Severe symptoms above AND
      2. Abdominal tenderness or distention
      3. Continuous bleeding needing transfusion

XVI. Grading: Lab and Exam based

  1. Moderate to severe criteria
    1. Serum Albumin <3.5 mg/dl (Severe: <3.0 mg/dl)
    2. Body Temperature >99 F or 37.2 C (Severe: >100 F or 37.8 C)
    3. Bowel Movements >4 per day (Severe: >6 per day)
    4. ESR >20 mm/hour (Severe: >30 mm/hour)
    5. Hematocrit <40% (Severe: <30%)
    6. Heart Rate >90 beats per minute (Severe: >100 beats per minute)
    7. Weight loss >1% (Severe: >10%)
  2. References
    1. Chang (2004) Gastroenterol Clin North Am 33:236 [PubMed]

XVII. Management: Approach

  1. Mild to moderate distal colitis
    1. When remission occurs with any step, transition to maintenance dosing of current agent
    2. Step 1: Topical 5-ASA at active dose per Rectum for 4-6 weeks
      1. Suppository for isolated Proctitis
      2. Enema for more proximal, left-sided Ulcerative Colitis
    3. Step 2: Consider ADDing shortterm rectal Corticosteroids
      1. Hydrocortisone enema (Cortenema) or if enema not retained, then foam (Cortifoam, Uceris)
    4. Step 3: ADD oral 5-ASA at active dose for 4-6 weeks (while continuing rectal 5-ASA)
    5. Step 4: Go to step 2 under mild-moderate extensive colitis
  2. Mild to moderate extensive colitis
    1. Step 1: Oral 5-ASA at active dose for 4-6 weeks
      1. If remission occurs, continue oral 5-ASA at maintenance dosing
    2. Step 2: Oral Corticosteroids for 4-6 weeks
      1. If remission occurs, transition to Azathioprine (Imuran) at maintenance dosing
    3. Step 3: Infliximab (Remicade) for 4-6 weeks
      1. If remission occurs, continue Infliximab at maintenance dosing
    4. Step 4: Consider third-line medications
      1. Intravenous Corticosteroids
      2. Cyclosporine (Sandimmune)
    5. Step 5: Consider surgical intervention
      1. See Colectomy below
  3. Severe to fulminant colitis
    1. Hospital admission
    2. Step 1: Corticosteroids IV at active dose for 3-5 days
      1. If remission occurs, transition to Azathioprine (Imuran) at maintenance dosing
    3. Step 2: Consider third-line medications
      1. Cyclosporine (Sandimmune) for 3-5 days
        1. If remission occurs, transition to Azathioprine (Imuran) at maintenance dosing
      2. Infliximab (Remicade) for 3-5 days
        1. If remission occurs, continue Infliximab at maintenance dosing
    4. Step 3: Consider surgical intervention
      1. See Colectomy below
  4. References
    1. Adams (2013) Am Fam Physician 87(10): 699-705 [PubMed]
    2. Kornbluth (2010) Am J Gastroenterol 105(3): 501-23 [PubMed]

XVIII. Management: Mild to Moderate disease

  1. Agents: 5-Aminosalicylic Acid Derivatives (5-ASA agents)
    1. No Sulfa Allergy: Sulfasalazine (Azulfidine)
      1. Often avoided in favor of 5-ASA agents
        1. Sulfasalazine is dosed four times daily, and is associated with Headache, Nausea, rash
      2. Active disease: Sulfasalazine 4-6 grams/day divided four times daily
      3. Maintenanance: Sulfasalazine 2-4 grams/day divided four times daily
    2. Sulfa Allergy: 5-Aminosalicylic acid (5-ASA, Mesalamine, Asacol, Pentasa)
      1. Oral (Asacol)
        1. Active disease: 2.4 to 4.8 grams/day divided 3 times daily
        2. Maintenance: 1.2 to 2.4 grams/day divided 3 times daily
      2. Suppository (Canasa)
        1. Active disease: 1000 mg once daily
        2. Maintenance: 500 mg once to twice daily
      3. Enema (Rowasa)
        1. Active disease: 1 to 4 grams daily
        2. Maintenance: 2-4 grams daily to every third day
    3. Other 5-ASA agents
      1. Olsalazine (Dipentum) 500 mg PO bid
      2. Lialda (Mesalamine) once daily
      3. Balsalazide (Colazal, Mesalamine) dosed three times daily
  2. Duration of medication use: 6-12 weeks
    1. Taper preparations to prevent rebound
  3. Route
    1. Rectal suppositories are preferred for Proctitis
    2. Use oral and rectal agents together for pancolitis
    3. Combined oral and rectal agents are more effective than either one alone

XIX. Management: Moderate to Severe disease

  1. Precaution
    1. Use only to stabilize active Ulcerative Colitis
    2. Avoid chronic use as these do not maintain remission and have serious longterm adverse effects
  2. Corticosteroids: Systemic
    1. Agents
      1. Prednisone 40-60 mg/day orally until improving, then decrease daily dose by 5-10 mg each week
      2. Methylprednisolone (Medrol) 40-60 mg/day orally
      3. Hydrocortisone (Cortef) 200-300 mg/day orally
      4. Methylprednisolone (Solu-Medrol) 40 mg IV daily
    2. Taper Corticosteroids gradually to prevent rebound
      1. Continue starting dose until clinical response (typically 10-14 days)
      2. After response, reduce dose by 5mg per week
    3. Efficacy
      1. Systemic Corticosteroids do not maintain remission and have serious side effects
  3. Coticosteroids: Uceris
    1. Uceris is a very expensive ($1200/month) oral budesonide tablet that primarily works locally in colon
    2. Contrast with Entocort EC that targets ileum and ascending colon in Crohn's Disease
    3. Contrast with Systemic Corticosteroids with their multitude of adverse effects
      1. Uceris Systemic Corticosteroid effects are increased with CYP3A4 Inhibitors
    4. Criscuoli (2013) Gastroenterology 144(3):e23 [PubMed]
  4. Corticosteroids: Rectal (for distal Ulcerative Colitis)
    1. Hydrocortisone Enema (Cortenema) 100 mg daily to twice daily
    2. Hydrocortisone Acetate 10% rectal foam (Cortifoam) 90 mg once to twice daily
  5. Disposition
    1. Hospitalization required when cases refractory to oral steroids and possibly outpatient Infliximab trial or
    2. Acute Abdomen or systemic toxicity

XX. Management: Immunosuppressants for Refractory disease

  1. Indications:
    1. Poor control with Corticosteroids
    2. Serious Corticosteroid complications
    3. Steroid dependent to control symptoms
    4. May avert surgical resection
  2. Agents
    1. Infliximab (Remicade)
      1. Active Disease: 5-10 mg/kg on weeks 0, 2 and 6
      2. Maintenance: 5-10 mg/kg every 4-8 weeks
    2. Azathioprine (Imuran)
      1. Active Disease: Not indicated
      2. Maintenance: 50-100 mg/day
    3. Cyclosporine (Sandimmune)
      1. Active Disease: 2-4 mg/kg/day
        1. Consider in acute cases refractory to IV Corticosteroids
      2. Maintenance: Not indicated
    4. 6-Mercaptopurine (Purinethol)
    5. Xeljanz (Tofacitinib)
      1. Oral Monoclonal Antibody available in 2019
  3. Duration
    1. For long term therapy only
    2. Ineffective for acute dx
    3. Onset of action: 2-6 months
  4. Complications
    1. Pancreatitis
    2. Infection risk
    3. Hepatitis
    4. Bone Marrow suppression (Follow Complete Blood Count)

XXI. Management: Surgery

  1. Surgical management of Ulcerative Colitis is curative
  2. Indications
    1. Medical failure
    2. Corticosteroid intolerance
    3. Growth retardation in children
    4. Dysplasia or malignancy
    5. Fulminant colitis with or without Megacolon
      1. Perforation
      2. Peritonitis
      3. Hemorrhage
  3. Procedures
    1. Total proctocolectomy (Brooke ileostomy)
      1. Completely cures Ulcerative Colitis
      2. Entire colorectal mucosa is excised
      3. Results in gas or Stool Incontinence
      4. Requires external collecting bag
      5. High rate of re-operation (>50%) due to post-surgical complication
    2. Ileal pouch anal anastomosis
      1. Patient maintains anal function and continence
      2. Pouchitis occurs in 30-50% of patients
  4. Complications
    1. Colonic stricture and increased risk of Bowel Obstruction
    2. Pouchitis or Pouch dysfunction
  5. References
    1. Cima (2005) Arch Surg 140:300-10 [PubMed]

XXII. Complications

  1. Colon Cancer (Adenocarcinoma)
    1. See monitoring below
    2. Colon Cancer risk is not increased in disease limited to Proctitis or proctosigmoiditis
    3. Risk increases with duration since diagnosis
      1. First 10 years: 2% risk
      2. First 20 years: 8% risk
      3. First 30 years: 18% risk
    4. References
      1. Eaden (2001) Gut 48:526-35 [PubMed]
  2. Toxic Megacolon
  3. Bowel Perforation
  4. Colonic Stricture
  5. Gastrointestinal Bleeding

XXIII. Monitoring: Colon Cancer

  1. General Colonoscopy approach
    1. Biopsies taken from cecum to Rectum every 10 cm
  2. Pancolitis
    1. Colonoscopy every 1-2 years after 8-10 years of disease
  3. Left-sided Colitis
    1. Colonoscopy every 3 years after 12-15 years of disease (British use 15-20 years)

XXIV. Course: Following initial attack of Ulcerative Colitis

  1. Continuous active Ulcerative Colitis: 75%
  2. Remission for 15 years: 10%
  3. Mortality within 1 year of initial attack: 5%
  4. Undergo total proctocolectomy within 5 years: 25%

XXV. Prevention: Probiotics for maintenance of remission

Images: Related links to external sites (from Bing)

Related Studies

Ontology: Ulcerative Colitis (C0009324)

Definition (MEDLINEPLUS)

Ulcerative colitis (UC) is a disease that causes inflammation and sores, called ulcers, in the lining of the rectum and colon. It is one of a group of diseases called inflammatory bowel disease.

UC can happen at any age, but it usually starts between the ages of 15 and 30. It tends to run in families. The most common symptoms are pain in the abdomen and blood or pus in diarrhea. Other symptoms may include

  • Anemia
  • Severe tiredness
  • Weight loss
  • Loss of appetite
  • Bleeding from the rectum
  • Sores on the skin
  • Joint pain
  • Growth failure in children

About half of people with UC have mild symptoms.

Doctors use blood tests, stool tests, colonoscopy or sigmoidoscopy, and imaging tests to diagnose UC. Several types of drugs can help control it. Some people have long periods of remission, when they are free of symptoms. In severe cases, doctors must remove the colon.

NIH: National Institute of Diabetes and Digestive and Kidney Diseases

Definition (MSHCZE) Zánět tlustého střeva provázený tvorbou vředů, viz colitis ulcerosa, proktokolitida. (cit. Velký lékařský slovník online, 2013 http://lekarske.slovniky.cz/ )
Definition (NCI) An inflammatory bowel disease involving the mucosal surface of the large intestine and rectum. It may present with an acute or slow onset and follows an intermittent or continuous course. Signs and symptoms include abdominal pain, diarrhea, fever, weight loss, and intestinal hemorrhage.
Definition (NCI_NCI-GLOSS) Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel.
Definition (CSP) chronic, recurrent ulceration of the colon mucosa and submucosa.
Definition (MSH) Inflammation of the COLON that is predominantly confined to the MUCOSA. Its major symptoms include DIARRHEA, rectal BLEEDING, the passage of MUCUS, and ABDOMINAL PAIN.
Concepts Disease or Syndrome (T047)
MSH D003093
ICD9 556.9, 556
ICD10 K51 , K51.9
SnomedCT 68195006, 27701000, 196985000, 196996008, 196988003, 266447004, 155764007, 64766004
English Colitis, Ulcerative, COLITIS ULCERATIVE, Idiopathic proctocolitis NOS, Ulcerative colitis, unspecified, ulcerative colitis, ulcerative colitis (diagnosis), Colitis ulcerative, UC, ULCERATIVE COLITIS, Ulceratve colitis unspcf, Colitis, Ulcerative [Disease/Finding], colitis ulcerative, Colitis;ulcerative, Proctocolitis idiopathic, Idiopathic Proctocolitis, Inflammatory Bowel Disease, Ulcerative Colitis Type, Colitis Gravis, Idiopathic proctocolitis (disorder), Idiopathic proctocolitis NOS (disorder), Proctocolitis, idiopathic, Ulcerative colitis, Colitis gravis, Ulcerative colitis (disorder), colitis; ulcerative, ulcerative; colitis, Colitis gravis, NOS, Ulcerative colitis, NOS, Idiopathic proctocolitis -RETIRED-, Ulcerative Colitis, idiopathic proctocolitis, Idiopathic proctocolitis, UC - Ulcerative colitis
French COLITE ULCEREUSE, Colite ulcérative, Colite ulcérative, non précisée, RCH (RectoColite Hémorragique), Rectocolite ulcéro-hémorragique, Colite cryptogénétique, Rectocolite muco-hémorragique, Rectocolite hémorragique, Rectocolite hémorragique et purulente, Colite suppurante, Proctocolite idiopathique, Colite ulcéreuse, RCUH
German COLITIS ULCEROSA, ulzerative Kolitis, unspezifisch, UC, ulzerative Kolitis, Colitis ulcerosa, nicht naeher bezeichnet, idiopathische Proktokolitis, Proktokolitis, idiopathisch, Kolitis ulcerosa, Colitis ulcerosa, Proctocolitis haemorrhagica, Proctocolitis ulcerosa, Rectocolitis haemorrhagica, Rectocolitis ulcerosa
Spanish colitis ulcerosa (trastorno), colitis ulcerosa, Colitis ulcerosa no especificada, CU (colitis ulcerosa), COLITIS ULCEROSA, proctocolitis idiopática, proctocolitis idiopática - RETIRADO - (concepto no activo), coloproctitis idiopática, proctocolitis idiopática - RETIRADO -, proctocolitis idiopática, SAI (trastorno), proctocolitis idiopática, SAI, Proctocolitis idiopática, Colitis ulcerosa, colitis grave, Colitis Ulcerosa
Italian Colite ulcerativa, Colite ulcerosa, non specificata, Proctocolite idiopatica, Colite ulcerosa
Dutch ulceratieve colitis, niet-gespecificeerd, ulceratieve colitis, proctocolitis, idiopathisch, idiopathische proctocolitis, colitis; ulceratief, ulceratief; colitis, Colitis ulcerosa, niet gespecificeerd, colitis ulcerosa, Colitis ulcerosa
Portuguese Colite ulcerosa NE, COLITE ULCEROSA, Proctocolite idiopática, Colite ulcerosa, Colite Ulcerativa
Japanese 潰瘍性大腸炎、詳細不明, カイヨウセイダイチョウエンショウサイフメイ, カイヨウセイダイチョウエン, 潰瘍性結腸炎, 大腸炎-潰瘍性, トクハツセイチョクチョウケッチョウエン, 特発性直腸結腸炎, 潰瘍性大腸炎, 結腸炎-潰瘍性
Swedish Kolit, ulcerös
Finnish Haavainen koliitti
Czech Ulcerózní kolitida, blíže neurčená, Ulcerózní kolitida, kolitida ulcerózní, ulcerózní kolitida, colitis ulcerosa, Idiopatická proktokolitida
Korean 궤양성 대장염(큰창자염), 상세불명의 궤양성 대장염(큰창자염)
Polish Zapalenie jelita grubego wrzodziejące
Hungarian Colitis ulcerosa, Colitis ulcerosa, nem meghatározott, Kifekélyesedő vastagbélgyulladás, CU (colitis ulcerosa), Proctocolitis, idiopathiás, Idiopathiás proctocolitis
Norwegian Kolitt, ulcerøs, Ulcerøs kolitt