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Ulcerative Colitis Last Updated: October 4, 2005 |
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| Synonyms and related keywords: continuous idiopathic inflammation of the colonic or rectal mucosa, colon, toxic megacolon, perforation, obstruction, ileus, inflammatory bowel disease, IBD, Crohn's disease, Crohn disease, primary sclerosing cholangitis, rectal bleeding, bloody bowel movements
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AUTHOR INFORMATION
| Section 1 of 11   |
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| Author: M Bashar Al-Ataie, MD, Consulting Staff, Department of Internal Medicine, Holzer Clinic and Holzer Medical Center Coauthor(s): Vishwanath N Shenoy, MD, Consulting Staff, Department of Gastroenterology, Holzer Clinic and Holzer Medical Center |
| M Bashar Al-Ataie, MD, is a member of the following medical societies:
American College of Physicians,
American Medical Association, and
Ohio State Medical Association |
| Editor(s): Anil Minocha, MD, FACP, FACG, Clinical Professor, School of Pharmary, Professor of Medicine, Director of Digestive Diseases, Medical Director of Nutrition Support, Medical Director of Gastrointestinal Endoscopy, Internal Medicine Department, University of Mississippi Medical Center; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine;
Noel Williams, MD, Professor Emeritus, Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada; Professor, Department of Internal Medicine, Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada;
Alex J Mechaber, MD, FACP, Assistant Dean for Medical Curriculum, Associate Professor of Medicine, Division of General Internal Medicine, University of Miami Miller School of Medicine;
and Julian Katz, MD, Clinical Professor of Medicine, Drexel University College of Medicine; Consulting Staff, Department of Medicine, Section of Gastroenterology and Hepatology, Hospital of the Medical College of Pennsylvania |
Disclosure
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INTRODUCTION
| Section 2 of 11   |
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Background: Ulcerative colitis is a relatively uncommon, chronic, recurrent inflammatory disease of the colon or rectal mucosa. Often a lifelong illness, the condition has profound emotional and social impact on the affected individual. Pathophysiology: Ulcerative colitis is defined as continuous idiopathic inflammation of the colonic or rectal mucosa. The rectum is involved in more than 95% of cases. Some authorities believe that the rectum is always involved in an untreated patient. Partial healing may occur in a patient treated with topical therapy, creating diagnostic confusion. Frequency:
- In the US: The annual incidence of ulcerative colitis is 10.4-12 cases per 100,000 people. The prevalence rate is 35-100 cases per 100,000 people.
- Internationally: Prevalence rates may be lower in South America, Asia, and Africa.
Race:
- Ulcerative colitis occurs more frequently in white people.
- The incidence of ulcerative colitis is reported to be 2-4 times higher in Jewish people. However, recent population studies in North America do not completely support this assertion.
Sex: Ulcerative colitis seems to have a female preponderance. Ulcerative colitis affects 30% more females than males.
Age: The incidence of ulcerative colitis peaks in people aged 15-25 years and in people aged 55-65 years, although it can occur in people of any age.
History: - Frequent episodes of rectal bleeding occur, with or without mucus. The characteristic feature is blood in each bowel movement.
- Weight loss in severe cases
- Extracolonic manifestations
- Ankylosing spondylitis (HLA-B27)
- Primary sclerosing cholangitis
- Rarely, thromboembolic events or syndromes (CNS venous thrombosis)
Physical: - Blood on digital rectal examination
Causes: - Autoimmune phenomena: Serum and mucosal autoantibodies against intestinal epithelial cells may be involved. Persons with ulcerative colitis are often found to have p-antineutrophil cytoplasmic antibodies.
- Immune-mediated phenomena: Abnormalities of humoral and cell-mediated immunity and/or generalized enhanced reactivity against intestinal bacterial antigens may be causes. A loss of tolerance against indigenous enteric flora is believed to be the central event in the pathogenesis of inflammatory bowel disease (IBD).
- Genetic susceptibility (chromosomes 12 and 16) is a factor associated with ulcerative colitis. A positive family history (observed in 1 in 6 relatives) is associated with a higher risk for developing the disease.
- Smoking is negatively associated with ulcerative colitis. This relationship is reversed in Crohn disease.
- Environmental factors may be involved.
- Dietary factors: Milk consumption may exacerbate the disease.
- Appendectomies have a negative association with ulcerative colitis.
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DIFFERENTIALS
| Section 4 of 11 |
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Colon Cancer, Adenocarcinoma
Rectal Cancer
Other Problems to be Considered:
Infectious colitis
Ischemic colitis in elderly patients
Radiation colitis
Collagenous colitis and lymphocytic colitis (rarely requires surgery, low risk for malignancy) |
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Lab Studies:
- Anemia (ie, hemoglobin <14 g/dL in males and <12 g/dL in females)
- Thrombocytosis (ie, platelet count >350,000/mL)
- Elevated sedimentation rate (variable reference ranges, usually 0-33 mm/h) and elevated C-reactive protein (ie, >100 mcg/L): Both of these findings correlate with disease activity.
- Hypoalbuminemia (ie, albumin <3.5 g/dL)
- Hypokalemia (ie, potassium <3.5 mEq/L)
- Hypomagnesemia (ie, magnesium <1.5 mg/dL)
- Elevated alkaline phosphatase: More than 125 U/L suggests primary sclerosing cholangitis (usually >3 times the upper limit of the reference range).
Imaging Studies:
- A plain abdominal radiograph might show colonic dilatation in severe cases, suggesting toxic megacolon. Also, evidence of perforation, obstruction, or ileus can be observed.
- Barium enemas may precipitate toxic megacolon in severe cases. Barium enemas can be performed safely in mild cases. They may show a narrow, tubular, shortened colon with loss of haustral folds, pseudopolyps, and small ulcers.
- Transabdominal bowel sonography (TABS) is a study that can be helpful in the diagnosis of IBD, but it cannot be used to distinguish between ulcerative colitis and Crohn disease. Note that transabdominal bowel sonography is different from regular abdominal ultrasound in which the bowel is actually excluded so that other structures in abdomen can be visualized.
- CT scan, in general, plays a minor role in the diagnosis of ulcerative colitis. CT scan can show thickening of the colonic wall. Biliary dilatation suggests primary sclerosing cholangitis.
- A radionuclide scan may be useful in acute fulminant colitis when colonoscopy or barium enemas are contraindicated. Also, it has been reported to be useful in diagnosing disease activity and extension.
Other Tests:
Procedures:
- Findings on flexible sigmoidoscopy can provide the diagnosis of colitis.
- Findings on colonoscopy with biopsy confirm a diagnosis. Also, this is useful for documenting the extent of the disease, for monitoring disease activity, and for surveillance for dysplasia or cancer; however, be cautious in attempting colonoscopy with biopsy in a patient with severe disease because of the possible risk of perforation or other complications.
Histologic Findings: Ulcerative colitis is characterized by a uniform inflammatory reaction in the colonic mucosa, without intervening areas of normal mucosa.
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TREATMENT
| Section 6 of 11 |
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Medical Care: See Medication. Surgical Care: Considerations for total colectomy are as follows: - Evidence of carcinoma or dysplasia
- Chronic refractory ulcerative colitis
- Severe hemorrhage or perforation
- Toxic megacolon cases that do not improve within 48-72 hours
- Obstruction due to stricture (be suspicious of cancer)
- Fulminant colitis not responsive to treatment
- Failure to thrive in children
Consultations: - Consultation with a surgeon for severe or fulminant colitis
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MEDICATION
| Section 7 of 11 |
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The goals of pharmacotherapy are to reduce morbidity and to prevent complications.
Drug Category: 5-Aminosalicylic acid agents -- Reduce inflammation. Drug Name
| Sulfasalazine (Azulfidine, EN-Tabs) -- Useful in the management of ulcerative colitis and acts locally in colon to decrease the inflammatory response and systemically inhibits prostaglandin synthesis. |
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| Adult Dose | 1 g PO tid/qid initially, followed by maintenance dose of 2 g/d in divided doses; use of full doses, ie 4 g/d, for maintenance therapy is increasing |
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| Pediatric Dose | <2 years: Not established.
>2 years: 40-60 mg/kg/d PO in 3-6 divided doses, followed by maintenance dose of 20-30 mg/kg/d divided qid| Contraindications | Documented hypersensitivity; GI obstruction; GU obstruction |
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| Interactions | Decreases effects of iron, digoxin, and folic acid; conversely, increases effect of oral anticoagulants, oral hypoglycemic agents, and methotrexate |
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| Pregnancy |
B - Usually safe but benefits must outweigh the risks.
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| Precautions | Caution in patients with renal or hepatic impairment, blood dyscrasias, or urinary obstruction; hypospermia |
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Drug Name
| Mesalamine (Asacol, Pentasa, Rowasa, Canasa) -- Better-tolerated sulfa-free drug with fewer adverse effects. Used in moderate active cases and as remission maintenance therapy. |
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| Adult Dose | Asacol: 400-mg tab, 2 tab PO tid
Pentasa: 250-mg cap, 4 cap PO qid
Rowasa enemas: 4 g/60 mL qhs
Canasa: Insert 1 supp PR bid| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity |
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| Interactions | Decreases effect of iron, digoxin, and folic acid; increases effect of oral anticoagulants, methotrexate, and oral hypoglycemic agents |
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| Pregnancy |
B - Usually safe but benefits must outweigh the risks.
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| Precautions | Elderly patients may have difficulty administering and retaining enemas; caution in patients with renal or hepatic impairment |
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Drug Name
| Balsalazide (Colazal) -- Prodrug converted into 5-aminosalicylic acid through bacterial azoreduction. Metabolites of the drug may decrease inflammation by blocking production of arachidonic acid metabolites in colon mucosa. |
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| Adult Dose | 3 cap (2.25 g) tid PO for 8-12 wk |
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity |
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| Interactions | Oral antibiotics may interfere with 5-aminosalicylic acid release in colon |
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| Pregnancy |
B - Usually safe but benefits must outweigh the risks.
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| Precautions | Caution in renal impairment; gastric retention of balsalazide may prolong in pyloric stenosis; safety and efficacy of long-term use (>12 wk) not established |
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Drug Category: Tumor necrosis factor (TNF) inhibitors -- TNF is a cytokine of which 2 forms have been identified with similar biological properties. TNF-alpha or cachectin is produced predominantly by macrophages, and TNF-beta or lymphotoxin is produced by lymphocytes. TNF is but one of many cytokines involved in the inflammatory cascade that may contribute to symptoms.Drug Name
| Infliximab (Remicade) -- Neutralizes cytokine TNF-alpha and inhibits its binding to TNF-alpha receptor. Mix in 250-cc normal saline for infusion over 2 h. Must use with low-protein-binding filter (1.2 micrometers or less). Indicated for moderate-to-severe active ulcerative colitis in patients who have experienced inadequate response to conventional therapy. Shown to reduce signs and symptoms, achieve clinical remission and mucosal healing, and eliminate corticosteroid use. |
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| Adult Dose | Ulcerative colitis/IBD/Crohn disease/psoriatic arthritis:
5 mg/kg IV infusion at 0, 2, and 6 wk as induction regimen, then 5 mg/kg q8wk for maintenance
IV infusion must be administered over at least 2 h; must use infusion set with in-line, sterile, nonpyrogenic, low-protein-binding filter (pore size <1.2 micrometers)| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity |
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| Interactions | None reported |
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| Pregnancy |
C - Safety for use during pregnancy has not been established.
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| Precautions | TNF-alpha modulates cellular immune responses; anti-TNF therapies, such as infliximab, may adversely affect normal immune responses and allow development of superinfections; more cases of lymphoma were observed in TNF-alpha blockers compared to controlled groups; may increase risk of reactivation of tuberculosis in patients with particular granulomatous infections |
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Drug Category: Immunosuppressants -- Inhibit activity of the immune system.Drug Name
| Azathioprine (Imuran) -- Used for long-term treatment in steroid-dependent cases or for patients who do not respond to aminosalicylate or corticosteroids. |
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| Adult Dose | 1.5-2.5 mg/kg/d PO |
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity; low levels of serum thiopurine methyltransferase (TPMT); patients who were treated with alkylating agents (eg, cyclophosphamide, chlorambucil, melphalan) |
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| Interactions | Toxicity increases with allopurinol; concurrent use with ACE inhibitors may induce severe leukopenia; may increase levels of methotrexate metabolites and decrease effects of anticoagulants, neuromuscular blockers, and cyclosporine |
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| Pregnancy |
D - Unsafe in pregnancy
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| Precautions | Increases risk of neoplasia in general but is controversial among patients with inflammatory bowel disease; caution in patients with liver disease and renal impairment; hematologic toxicities may occur; check TPMT level prior to therapy and monitor liver, renal, and hematologic function; pancreatitis rarely is associated |
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Drug Name
| Cyclosporine (Neoral, Sandimmune) -- Used in acute severe ulcerative colitis refractory to intravenous corticosteroids. |
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| Adult Dose | 4 mg/kg/d IV infusion
2-3 mg/kg/d in elderly patients or in patients with renal dysfunction| Pediatric Dose | Administer as in adults |
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| Contraindications | Documented hypersensitivity; uncontrolled hypertension or malignancies; do not administer concomitantly with PUVA or UVB radiation in psoriasis because it may increase risk of cancer |
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| Interactions | Carbamazepine, phenytoin, isoniazid, rifampin, and phenobarbital may decrease cyclosporine concentrations; azithromycin, itraconazole, nicardipine, ketoconazole, fluconazole, erythromycin, verapamil, grapefruit juice, diltiazem, aminoglycosides, acyclovir, amphotericin B, and clarithromycin may increase cyclosporine toxicity; acute renal failure,
rhabdomyolysis, myositis, and myalgias increase when taken concurrently with lovastatin| Pregnancy |
C - Safety for use during pregnancy has not been established.
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| Precautions | Evaluate renal and liver functions often by measuring BUN, serum creatinine, serum bilirubin, and liver enzymes; may increase risk of infection and lymphoma; increases risk of seizures |
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Drug Name
| 6-Mercaptopurine (Purinethol) -- Used for long-term treatment in steroid-dependent cases, or for patients who do not respond to aminosalicylate or corticosteroids. |
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| Adult Dose | 1.5 mg/kg/d PO |
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity |
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| Interactions | Toxicity increases when administered with allopurinol; hepatic toxicity increases when used in combination with doxorubicin |
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| Pregnancy |
D - Unsafe in pregnancy
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| Precautions | Exercise caution in patients diagnosed with renal or hepatic impairment; patients on this medication have a high risk of developing pancreatitis, monitor for myelosuppression |
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Drug Category: Antimicrobials -- Ciprofloxacin and metronidazole usually are administered on an empiric basis in patients with severe colitis in addition to steroids. Also, these are used for the treatment of pouchitis after colectomy and ileoanal anastomosis.Drug Name
| Ciprofloxacin (Cipro) -- Fluoroquinolone with activity against pseudomonads, streptococci, MRSA, Staphylococcus epidermidis, and most gram-negative organisms but no activity against anaerobes. Inhibits bacterial DNA synthesis and, consequently, growth. |
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| Adult Dose | 500 mg PO bid
400 mg IV bid| Pediatric Dose | <18 years: Not recommended
>18 years: Administer as in adults| Contraindications | Documented hypersensitivity |
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| Interactions | Antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after taking fluoroquinolones; cimetidine may
interfere with metabolism of fluoroquinolones; ciprofloxacin reduces therapeutic effects of phenytoin; probenecid may increase ciprofloxacin
serum concentrations; may increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT)| Pregnancy |
C - Safety for use during pregnancy has not been established.
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| Precautions | In prolonged therapy, perform periodic evaluations of organ system functions (eg, renal, hepatic, hematopoietic); adjust dose in patients with renal function impairment; superinfections may occur with prolonged or repeated antibiotic therapy |
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Drug Name
| Metronidazole (Flagyl) -- Imidazole ring-based antibiotic active against various anaerobic bacteria and protozoa. Used in combination with other antimicrobial agents (except for C difficile enterocolitis). |
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| Adult Dose | Loading dose: 15 mg/kg (or 1 g for 70-kg adult) IV over 1 h
Maintenance dose: 6 h following loading dose, infuse 7.5 mg/kg (or 500 mg for 70-kg adult) over 1 h q6-8h; not to exceed 4 g/d| Pediatric Dose | Administer as in adults, using body weight |
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| Contraindications | Documented hypersensitivity |
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| Interactions | May increase toxicity of anticoagulants, lithium, and phenytoin; cimetidine may increase toxicity of metronidazole; disulfiram reaction may occur with orally ingested ethanol |
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| Pregnancy |
B - Usually safe but benefits must outweigh the risks.
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| Precautions | Adjust dose in patients with hepatic disease; monitor for seizures and development of peripheral neuropathy |
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Drug Category: Corticosteroids -- Used in severe active cases for induction of remission. They have no benefit in maintaining remission; long-term use can cause adverse effects.Drug Name
| Methylprednisolone (Solu-Medrol, Depo-Medrol, Medrol) -- Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability. Administered intravenously in severe cases. |
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| Adult Dose | 80 mg IV q8h; dose may vary |
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| Pediatric Dose | 60 mg IV q8h in severe or fulminant cases; dose may vary |
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| Contraindications | Documented hypersensitivity; premature infants; systemic fungal infections |
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| Interactions | Mutual inhibition of metabolism occurs with concomitant use of cyclosporine and methylprednisolone; convulsions have been reported when these medicines were used together; drugs that induce hepatic enzymes (eg, phenobarbital, phenytoin, rifampin) may increase clearance of methylprednisolone; troleandomycin and ketoconazole may inhibit the metabolism of methylprednisolone; may increase the clearance of long-term high-dose aspirin; variable effect on oral anticoagulants |
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| Pregnancy |
C - Safety for use during pregnancy has not been established.
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| Precautions | Acne, striae, and hirsutism; cataract and glaucoma; hypertension; glucose intolerance; adrenal suppression; osteoporosis and osteonecrosis; growth retardation in children; masking or induction of intestinal perforation |
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Drug Name
| Prednisone (Deltasone, Orasone, Meticorten) -- Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability. |
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| Adult Dose | 40-60 mg PO for 10-14 d, then taper off over 8-12 wk, using sulfasalazine or mesalamine as maintenance therapy |
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| Pediatric Dose | 4-5 mg/m2/d PO; alternatively, 0.05-2 mg/kg PO divided bid/qid |
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| Contraindications | Documented hypersensitivity; peptic ulcer disease; hepatic dysfunction; GI disease; connective tissue infections; viral infections; fungal or tubercular skin infections |
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| Interactions | Coadministration with estrogens may decrease prednisone clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics |
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| Pregnancy |
B - Usually safe but benefits must outweigh the risks.
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| Precautions | Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use |
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FOLLOW-UP
| Section 8 of 11 |
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Further Outpatient Care:
- Surveillance colonoscopy is recommended; however, the optimum interval for performing screening colonoscopy remains unclear. In general, surveillance colonoscopy is recommended as follows:
- Extensive biopsies should be obtained every 1-2 years in patients with extensive disease or pancolitis or in patients who have had the disease for 8 or more years.
- Extensive biopsies should be obtained after 12-15 years in patients with left-sided disease.
- If high-grade dysplasia or cancer is found, colectomy is performed.
- If low-grade dysplasia is found, colonoscopy should be repeated regularly (ie, 3-6 mo).
Complications:
- Toxic megacolon occurs in less than 2% of cases and can be induced by hypokalemia, opiates, anticholinergics, and barium enemas. Patients are acutely ill. Conservative treatment can be tried for 24-48 hours with IV fluids, IV steroids, antibiotics, and IV cyclosporine. Patients may need a total colectomy.
- The risk of colorectal cancer increases by 0.5-1% per year. Regular surveillance is needed.
Prognosis:
- Most cases are controlled with medical therapies, with the patient experiencing lifelong exacerbations and remissions. In more severe cases, surgery results in a cure.
Patient Education:
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MISCELLANEOUS
| Section 9 of 11 |
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Medical/Legal Pitfalls:
- Colonoscopy performed in severe cases can result in complications.
- Barium enemas performed in some severe cases can precipitate toxic megacolon.
- Patients with extensive disease for 8 years or those with left-sided colitis for more than 15 years need a colonoscopy every 1-3 years to screen for colon cancer.
Special Concerns:
- Sclerosing cholangitis and cholangiocarcinoma
- Extracolonic manifestations
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PICTURES
| Section 10 of 11 |
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| Caption: Picture 1. Ulcerative colitis as visualized with a colonoscope.
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Picture Type: Photo |
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BIBLIOGRAPHY
| Section 11 of 11 |
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Brown MO: Inflammatory bowel disease. Prim Care 1999 Mar; 26(1): 141-70[Medline].
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Froehlich F, Larequi-Lauber T, Gonvers JJ: 11. Appropriateness of colonoscopy: inflammatory bowel disease. Endoscopy 1999 Oct; 31(8): 647-53[Medline].
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Hanauer SB: Inflammatory bowel disease. N Engl J Med 1996 Mar 28; 334(13): 841-8[Medline].
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Jaynathi V, Probert CJS, Mayberry JF: Epidemiology of Inflammatory Bowel Disease. Quarterly Journal of Medicine, New Series 78, January 1991; 285: 5-12.
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Kornbluth A: Immunomodulators in Ulcertive Colitis. Advanced Therapy of Inflammatory Bowel Disease 2001; 139-142.
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Rioux JD, Silverberg MS, Daly MJ: Genomewide search in Canadian families with inflammatory bowel disease reveals two novel susceptibility loci. Am J Hum Genet 2000 Jun; 66(6): 1863-70[Medline].
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Sands BE: Therapy of inflammatory bowel disease. Gastroenterology 2000 Feb; 118(2 Suppl 1): S68-82[Medline].
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Thomas GA, Rhodes J, Green JT: Role of smoking in inflammatory bowel disease: implications for therapy. Postgrad Med J 2000 May; 76(895): 273-9[Medline].
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Tremaine WJ: Collagenous colitis and lymphocytic colitis. J Clin Gastroenterol 2000 Apr; 30(3): 245-9[Medline].
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