eMedicine Specialties > Ophthalmology > Neurologic Disorders

Inflammatory Bowel Disease

Mounir Bashour, MD, CM, FRCS(C), PhD, FACS, Assistant Professor of Ophthalmology, McGill University; Clinical Assistant Professor of Ophthalmology, Sherbrooke University; Medical Director, Cornea Laser and Lasik MD

Updated: Jun 8, 2009

Introduction

Background

Inflammatory bowel disease (IBD) is used commonly to refer to the following 2 illnesses: ulcerative colitis (UC) and Crohn disease (CD). These chronic inflammatory diseases of the GI tract are of unknown etiology. CD is also referred to as regional enteritis, terminal ileitis, or granulomatous ileocolitis.

Pathophysiology

UC primarily involves the mucosa and the submucosa, with formation of crypt abscesses and mucosal ulceration. The mucosa typically appears granular and friable. In more severe cases, pseudopolyp formation occurs. These consist of areas of hyperplastic growth with swollen mucosa surrounded by inflamed mucosa with shallow ulcers. Although unusual, in severe UC, inflammation and necrosis can extend below the lamina propria to involve the submucosa and the circular and longitudinal muscles.

UC arises first in the rectum, where it remains confined in about 25% of cases. In the remainder, contiguous proximal spread occurs.

Pancolitis occurs in 10% of patients. The small intestine is never involved, except when the distal terminal ileum is inflamed in a superficial manner, referred to as backwash ileitis. Even with less than total colonic involvement, the disease is strikingly and uniformly continuous. As the disease becomes chronic, the colon becomes a rigid, foreshortened tube that lacks its usual haustral markings, leading to the lead pipe appearance seen on barium enema. No skip areas like those seen in CD of the colon are present.

CD consists of segmental involvement by a nonspecific granulomatous inflammatory process. The most important pathologic feature is that all the layers of the bowel are involved, not just the mucosa and the submucosa, as is characteristic of UC. Furthermore, the disease is discontinuous, with normal areas of bowel skip areas interspersed between one or more involved areas. Late in the disease, the mucosa develops a cobblestone appearance. This results from deep longitudinal ulcerations interlacing with intervening normal mucosa. The ileum is involved in most cases. However, in 20% of cases the disease is confined to the colon, often with rectal sparing.

Rectal involvement is unusual, but anorectal complications (eg, fistulas, abscesses) are common. One third of patients have disease limited to the small intestine, most commonly in the distal ileum. An increased incidence of gallstones and kidney stones occurs in CD, owing to malabsorption of fat and bile salts. Gallstones are formed because of increased cholesterol concentration in the bile due to a reduced bile salt pool. Calcium oxalate kidney stones are formed in patients with CD who have ileal disease or resection. With the resulting fat malabsorption, unabsorbed long-chain fatty acids bind calcium in the lumen.

Normally, oxalate in the lumen is bound to calcium. Calcium oxalate is poorly soluble and poorly absorbed. However, if calcium is bound to malabsorbed fatty acids, oxalate combines with sodium to form sodium oxalate, which is soluble and is absorbed in the colon (enteric hyperoxaluria). The development of calcium oxalate stones in CD requires an intact colon to absorb oxalate. Patients with ileostomies do not develop calcium oxalate stones.

Extraintestinal manifestations of both types of inflammatory bowel disease include iritis, episcleritis, arthritis, and skin involvement, as well as pericholangitis and sclerosing cholangitis.

Frequency

United States

Prevalence is 70-150 cases per 100,000 population.

Mortality/Morbidity

The quality of life generally is lower with CD than with UC, owing in part to recurrences after surgery.

• The most common causes of death in inflammatory bowel disease are peritonitis with sepsis, malignancy, thromboembolic disease, and complications of surgery. Toxic megacolon, one of the most dreaded complications of UC, can lead to perforation, sepsis, and death.
• Malnutrition and chronic anemia are seen in long-standing CD.
• Children can develop growth retardation.

Race

Incidence in whites is about 4 times that of other races.

• People in Northern Europe and North America are most commonly affected.
• An increased incidence is reported in Ashkenazi Jews, particularly those who have immigrated from Northern Europe.

Sex

Females are affected slightly more than males.

Age

Peak incidence is in the second and third decades of life. A second, smaller peak occurs in individuals aged 55-65 years.

Clinical

History

• UC presents most commonly with bloody diarrhea.
• Abdominal pain and cramping, fever, and weight loss occur in more severe cases. The greater the extent of colon involved, the more likely the patient is to have diarrhea.
• Rectal urgency or tenesmus reflects reduced compliance of the inflamed rectum.
• It is possible for patients to have formed stools if their disease is confined to the rectum.
• As the degree of inflammation increases, systemic symptoms develop. These symptoms may include low-grade fever, malaise, nausea, vomiting, sweats, and arthralgias.
• With severe UC, fever, dehydration, and abdominal tenderness develop, reflecting progressive inflammation into deeper layers of the colon.
• The presentation of CD is more chronic than that of UC, with ongoing abdominal pain, anorexia, diarrhea, weight loss, and fatigue.
• Whereas grossly bloody stools are typical of UC, they are less common in CD.
• Stools may be formed; however, if extensive involvement of the colon or terminal ileum is present, loose stools predominate.
• One half of patients with CD present with perianal disease (eg, fistulas, abscesses).
• On occasion, acute right lower quadrant pain and fever may be noted, mimicking appendicitis.
• Commonly, the diagnosis is established only after several years of recurrent abdominal pain, fever, and diarrhea. CD with gastroduodenal involvement may mimic peptic ulcer disease and can progress to gastric outlet obstruction.
• Many patients with IBD also have irritable bowel syndrome. The latter can produce occasional cramping, irregular bowel habits, and passage of mucus without blood or pus.
• Weight loss is seen more commonly in patients with CD than in patients with UC because of the malabsorption associated with small bowel disease. Patients may reduce their food intake in an effort to control their symptoms.
• Systemic symptoms are common and include fever, sweats, malaise, and arthralgias.
• Patients with toxic megacolon appear septic with high fever; lethargy; chills; tachycardia; and increasing abdominal pain, tenderness, and distention.
• Children may present with growth retardation and delayed or failed sexual maturation.
• In 10-20% of cases, patients present with extraintestinal manifestations, including arthritis, uveitis, or liver disease.
• Recurrences may occur with emotional stress, infections or other acute illnesses, pregnancy, dietary indiscretions, use of cathartics or antibiotics, or with withdrawal of anti-inflammatory or steroid medications.

Physical

• Fever, tachycardia, dehydration, and toxicity may be seen. The magnitude of these factors is related directly to the severity of the attack.
• Although abdominal tenderness is common, evaluate for signs of localized peritonitis. Patients with CD may develop a mass in the right lower quadrant.
• The rectal examination often reveals bloody stool on gross or Hemoccult examination.
• In as many as 90% of patients with CD, complications, such as perianal fissures or fistulas, abscesses, or rectal prolapse, may be seen.
• The examination should include a search for extraintestinal manifestations, such as iritis, episcleritis, arthritis, and dermatologic involvement.

Causes

The etiology of IBD is unknown. Environmental, infectious, genetic, autoimmune, and host factors have been suspected. More likely, interactions among these factors may be more important.

• Cigarette smoking appears to protect against UC, whereas it is associated with CD. On occasion, the onset of UC appears to occur upon smoking cessation.
• Inflammatory mediators  
  • Interleukin 1 (IL-1)
  • Tumor necrosis factor-alpha (TNF-alpha)
  • Aggravated by bacterial infection and inflammatory cascade

Differential Diagnoses

Other Problems to Be Considered

Diverticular disease 
Antibiotic-associated colitis
Arteriovenous malformations
Colon cancer
Fever of unknown origin
Infectious colitis (If confined to the rectum, rule out gay bowel syndrome.)
Ischemic colitis
Radiation-induced colitis

Workup

Laboratory Studies

• Complete blood count (CBC) with differential  
  • Anemia may result from acute or chronic blood loss or malabsorption (iron, folate, vitamin B-12) or reflect the chronic disease state.
  • Leukocytosis, anemia, and thrombocytosis are common.
  • The sedimentation rate typically is elevated.
• Chemistries
  • Hypokalemia reflects the severity of the diarrhea.
  • Abnormal LFTs may represent a pericholangitis or sclerosing cholangitis.
  • Hypoalbuminemia, resulting from protein-losing enteropathy, suggests extensive colitis.
  • A decreased serum calcium may reflect reduced serum albumin.
  • Blood culture results may be positive if peritonitis or fulminant colitis is present.
  • Obtain stool for fecal leukocytes, ova and parasite studies, culture for bacterial pathogens, and Clostridium difficile titer.

Imaging Studies

• Upright chest x-ray (CXR) and abdominal series  
  • Look for free air, and especially for evidence of toxic megacolon, which appears as a long, continuous segment of air-filled colon greater than 6 cm in diameter. In the supine position, dilatation is noted predominantly in the transverse colon because air collects there.
  • Obtain repeat films at 12- to 24-hour intervals to follow the course of dilatation and assess the need for emergency colectomy.
  • Associated findings include nephrolithiasis, cholelithiasis, or arthritis of the spine or sacroiliac joints.
• Barium enema
  • In UC, a barium enema (BE) may reveal a shortened colon, with loss of haustrations and destruction of the mucosal pattern (the lead pipe colon).
  • In CD, skip areas and rectal sparing are noted.
  • A BE is contraindicated in patients with moderate-to-severe colitis because it risks perforation or precipitation of a toxic megacolon.
• CT scan and ultrasound are best for demonstrating intra-abdominal abscesses, mesenteric inflammation, and fistulas.

Procedures

• Sigmoidoscopy may be diagnostic in UC, since the rectum always is involved.
• The mucosal surface becomes irregular and friable, bleeds easily when touched, and may have pseudopolyps.
• Colonoscopy is more sensitive for making the diagnosis and evaluating the extent and severity of disease.
• As with BE, these procedures should be avoided in acutely ill patients.

Histologic Findings

Ulcerative colitis - Inflammation confined to the mucosa and submucosa with polymorphonuclear leukocytosis within the lamina propria, crypt, and surface epithelium and crypt lumina

Crohn disease - Transmural, predominantly submucosal inflammation with a cobblestone appearance; submucosal edema, lymphoid aggregation, lymphoplasmacytic aggregation, and, ultimately, fibrosis. The hallmark finding is sarcoid-type epithelioid granulomas.

Treatment

Medical Care

Supportive care should be initiated with bowel rest, nasogastric suction, and intravenous fluids containing electrolytes.

• Admit for toxicity, obstruction, hemorrhage, or localized peritonitis.
• Monitor severe cases for fat malabsorption.
• Perirectal disease
  • Sitz baths
  • Soap and water after stooling
  • Surgical drainage of perirectal abscesses
  • Surgical treatment of recurrent fistulas if medical management fails
  • Folate supplementation, as needed

Surgical Care

One of the latest papers regarding surgery in IBD states the following:

Surgery is required in the vast majority of patients with Crohn's disease (CD) and in approximately one-third of patients with ulcerative colitis (UC). Similar to medical treatments for IBD, significant advances have occurred in surgery. Advances in CD include an emphasis upon conservatism as exemplified by more limited resections, strictureplasties, and laparoscopic resections. The use of probiotics in selected patients has improved the outcome in patients with pouchitis following restorative proctocolectomy for UC. It is anticipated that ongoing discoveries in the molecular basis of IBD will in turn identify those patients who will best respond to surgery.¹

Consultations

• Obtain surgical consultation if obstruction, hemorrhage, perforation, abscess or fistula formation, toxic megacolon, or perianal disease is present.
• Patients failing medical therapy also should be considered for surgical intervention.
• In patients with CD, the surgeon should resect only as much bowel as is necessary to correct the problem. Following surgery, the recurrence rate approaches 100%.
• Patients with toxic megacolon initially require nasogastric suction and intravenous steroids. Failure to improve within 48 hours is an indication for total colectomy.
• Extracolonic manifestations (ie, uveitis, arthritis, dermatitis, sclerosing cholangitis) are managed best with the aid of specialty consultation.

Medication

The latest review on medical therapy for IBD states: "While a cure remains elusive, both can be treated with medications that induce and maintain remission."²   Therapy for CD generally is less effective than for UC. Cholestyramine (Questran), a resin that binds bile salts, has been found to be useful for reducing diarrhea in patients with CD disease who have had ileal resections.

The anticholinergic, Bentyl, may help relieve intestinal spasms.

In addition to the therapies mentioned below, IV cyclosporine is helpful in refractory UC. Zileuton, a 5-lipoxygenase inhibitor, has shown some efficacy in CD. Hyperbaric oxygen therapy has been found helpful in the treatment of IBD unresponsive to other therapies. Its therapeutic efficacy appears to result from decreased generation of prostaglandin E2. Previous work has linked mucosal prostaglandin E2 to the intestinal damage associated with IBD.

Antidiarrheal agents

Agents for symptomatic treatment, loperamide and diphenoxylate, are useful in mild disease to reduce the number of bowel movements and relieve rectal urgency. Antidiarrheal and anticholinergic medications must be avoided in acute severe disease because they may precipitate toxic megacolon.

Loperamide (Imodium)

Acts in intestinal muscles to inhibit peristalsis and slow intestinal motility. Also prolongs movement of electrolytes and fluid through the bowel and increases viscosity and loss of fluids and electrolytes.

Dosing

Adult

4 mg PO initially, then 2 mg after each loose stool, not to exceed 16 mg/d

Pediatric

Initial doses:
2-6 years: 1 mg PO tid
6-8 years: 2 mg PO bid
8-12 years: 2 mg PO tid
Maintenance: 0.1 mg/kg PO after each loose stool; not to exceed initial dose
Chronic diarrhea: 0.08-0.24 mg/kg/d divided bid/tid; not to exceed 2 mg/dose

Interactions

Phenothiazines, tricyclic antidepressants, and CNS depressants may increase loperamide toxicity

Contraindications

Documented hypersensitivity; diarrhea resulting from infections; pseudomembranous colitis

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Discontinue use if no clinical improvement in 48 h; since loperamide primarily metabolized in liver, monitor for CNS toxicity in patients with hepatic insufficiency; do not use medication if high fever or blood in stool coincides with diarrhea

Dicyclomine (Bentyl)

Treats GI motility disturbances. Blocks the action of acetylcholine at parasympathetic sites in secretory glands, smooth muscle, and CNS.

Dosing

Adult

80 mg/d PO divided qid initially and increase to 160 mg/d

Pediatric

10 mg/dose PO tid/qid

Interactions

Effects are weakened when administered with anti-Parkinson drugs, haloperidol, and phenothiazines; toxicity of dicyclomine increases when administered concurrently with amantadine, antihistamines, type-I antiarrhythmics, phenothiazines, TCAs, or narcotic analgesics

Contraindications

Documented hypersensitivity; myasthenia gravis or narrow-angle glaucoma

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution when administering to patients with hepatic or renal insufficiency, cardiovascular disease, urinary tract obstruction, UC, GI obstruction, hyperthyroidism, or hypertension

Aminosalicylates

Effective for treating acute UC and for maintaining remission. Also beneficial in mildly to moderately active CD when colonic involvement is present. However, sulfasalazine has not clearly been shown to maintain remission in CD.

Newer aminosalicylates, which are 5-ASA preparations without sulfapyridine, were developed because tolerance of sulfasalazine has been limited by the sulfa-containing moiety. Since free 5-ASA is absorbed rapidly from proximal GI tract, it has been modified in newer formulations. Olsalazine (Dipentum) consists of 2 5-ASA molecules linked together by an azo bond. Bond is cleaved by intestinal bacteria, so that olsalazine works primarily in the colon.

Additional formulations of 5-ASA (mesalamine) are Asacol, Pentasa, and Rowasa. Asacol is composed of 5-ASA coated in a pH-dependent acrylic resin. This leads to delayed release of the 5-ASA in the distal ileum and right colon. Pentasa consists of 5-ASA encapsulated into microgranules of ethylcellulose and released continuously throughout the GI tract. Therefore, it is useful in patients with CD who have involvement of the small bowel and colon. Rowasa contains 5-ASA in suppository or enema formulations. This is useful for treating and maintaining remissions in ulcerative proctitis and proctosigmoiditis.

Sulfasalazine (Azulfidine)

Combination or mesalamine and sulfapyridine. Taken orally, remains intact until it reaches terminal ileum and colon, where it is split by bacteria into 2 moieties. Active portion appears to be 5-ASA, which inhibits prostaglandin synthesis. The sulfa portion is absorbed and is the cause of most of adverse reactions.
Abdominal discomfort is common. Folate deficiency may result from competition between folate and sulfasalazine for absorption.

Dosing

Adult

3-4 g PO qd in divided doses

Pediatric

<2 years: Not established
>2 years: 40-60 mg/kg/d PO in 3-6 divided doses; follow by maintenance dose of 20-30 mg/kg/d divided qid

Interactions

Decreases effects of iron, digoxin, and folic acid; conversely, increases effect of oral anticoagulants, oral hypoglycemic agents, and methotrexate

Contraindications

Documented hypersensitivity; sulfa drugs, or any component and those diagnosed with GI or GU obstruction

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in patients with renal or hepatic impairment, blood dyscrasias, or urinary obstruction

Olsalazine (Dipentum)

Alternative treatment for patients that do not tolerate sulfasalazine. Useful in maintaining remission of UC. In addition, has anti-inflammatory activity in UC.

Dosing

Adult

500 mg PO bid

Pediatric

Not established

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

A relatively high incidence of diarrhea appears to be associated with this treatment and may be dose related; unclear whether other underlying causes may contribute to high incidence.

Corticosteroids

Treatment of choice for an acute attack and should be administered IV in severe disease. Give increased or stress doses, to those patients who are already on steroids.

Steroids should not be used for maintaining a remission because of the lack of efficacy and potential complications, including avascular necrosis, osteoporosis, cataracts, emotional lability, hypertension, diabetes, Cushingoid features, acne, and facial hair.

Cortenema, Cortifoam, and Anusol-HC suppositories are useful for treatment of distal disease (proctitis and proctosigmoiditis).

Prednisone (Deltasone)

Immunosuppressant for treatment of autoimmune disorders; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.

Dosing

Adult

5-60 mg/d qd or divided bid/qid

Pediatric

4-5 mg/m²/d PO
Alternatively, administer 1-2 mg/kg PO qd; taper over 2 wk as symptoms resolve

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

Contraindications

Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective tissue infections and fungal or tubercular skin infections; GI disease

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

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

Methylprednisolone (Adlone, Medrol, Solu-Medrol)

Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.

Dosing

Adult

Loading dose: 125-250 mg IV
Maintenance dose: 0.5-1 mg/kg/dose IV q6h for up to 5 d

Pediatric

Loading dose: 2 mg/kg IV
Maintenance dose: Administer as in adults

Interactions

Coadministration with digoxin may increase digitalis toxicity secondary to hypokalemia; estrogens may increase levels of methylprednisolone; phenobarbital, phenytoin, and rifampin may decrease levels of methylprednisolone (adjust dose); monitor patients for hypokalemia when taking medication concurrently with diuretics

Contraindications

Documented hypersensitivity; viral, fungal, or tubercular skin infections

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Hyperglycemia, edema, osteonecrosis, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, myopathy, and infections are possible complications of glucocorticoid use

Immunosuppressants

These agents are useful as steroid-sparing agents, in healing fistulas, or when serious contraindications to surgery exist. Also used in those patients refractory to or unable to tolerate steroids. Some of these agents, including azathioprine and its metabolite, 6-mercaptopurine, have been useful in CD complicated by recurrent rectal fistulas or perianal disease. However, a response can take as long as 6 months. Methotrexate also has been used.

Azathioprine (Imuran)

Antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. May decrease proliferation of immune cells, which results in lower autoimmune activity.

Dosing

Adult

1 mg/kg/d PO for 6-8 wk and increase by 0.5 mg/kg q4wk until there is response or has reached a dose of 2.5 mg/kg/d

Pediatric

Initial dose: 2-5 mg/kg/d PO/IV
Maintenance dose: 1-2 mg/kg/d PO/IV

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

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Increases risk of neoplasia; caution with liver disease and renal impairment; hematologic toxicities may occur

Antibiotics

For fulminant disease including toxic megacolon, institute parenteral antibiotics active against coliforms and anaerobes. These may include metronidazole, ampicillin or a cephalosporin, and an aminoglycoside.

Metronidazole (Flagyl)

Useful in the treatment of a fulminant disease but specifically mentioned here because has been used successfully in CD complicated by perianal ulcers, perirectal abscesses, and fistulas. Not clear whether this drug is active because of its antibacterial properties or through some other mechanism.

Dosing

Adult

20 mg/kg/d PO in divided doses

Pediatric

Not established

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

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Increases risk of neoplasia; caution with liver disease and renal impairment; hematologic toxicities may occur

Monoclonal antibodies

A study reported that 33% of patients with moderate-to-severe CD went into remission after receiving a single infusion of monoclonal antibodies to TNF-alpha. Infliximab (Remicade) has been approved for IV treatment of moderate-to-severe CD refractory to other medical treatment. In August 2005, infliximab was also approved for UC.

Infliximab (Remicade)

Neutralizes cytokine TNF-alpha and inhibits its binding to TNF-alpha receptor.

Dosing

Adult

5 mg/kg as single IV infusion
For long-term treatment, 5 mg/kg IV infusion at 0, 2, and 6 wk as an induction regimen is administered, 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

Not established

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

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

Follow-up

Further Outpatient Care

• In CD, nutritional support includes supplementation with trace metals, fat-soluble vitamins, and medium-chain triglycerides.
• A low oxalate diet with citrate supplementation helps to reduce the risk of nephrolithiasis.
• Oral calcium or cholestyramine may serve as intestinal oxalate binders.

Complications

• Gastrointestinal
  • Perforation and toxic megacolon are the most dreaded complications of UC. Perforation can occur in the presence of fulminating disease, even in the absence of toxic megacolon.
  • If perforation occurs, the mortality rate is 50%.
  • Suspect toxic megacolon in a patient with fulminant UC, especially when a sharp decline has occurred in the number of daily stools but without a corresponding improvement in symptoms. The abdomen typically is distended, tender, and tympanitic. Toxic megacolon can be precipitated by antidiarrheal agents, hypokalemia, narcotics, cathartics, and enemas, including BEs. It is diagnosed best on plain films. A colectomy is required if no improvement occurs within 24-48 hours.
• Strictures
  • Usually, strictures are benign but can lead to obstruction.
  • Fistulas and abscesses are much more common in patients with CD but are seen in about 20% of patients with UC.
  • Fistulas include enterovesical (leading to recurrent urinary tract infections and pneumaturia), enteroenteric, enteromesenteric, enterocutaneous, rectovaginal, and perianal.
  • Additional problems include stenosis and obstruction.
  • Perianal complications occur in 90% of patients with CD.
  • In CD, obstructive hydronephrosis may result from a right lower quadrant inflammatory mass, leading to external compression of the right ureter.
  • Massive hemorrhage occurs in fewer than 1% of patients.
• Cancer
  • UC carries a 10- to 30-fold increase in the development of carcinoma of the colon.
  • The risk increases with extent and duration of the disease.
  • The cumulative risk of cancer after 15, 20, and 25 years is 8%, 12%, and 25%, respectively.
  • Periodic colonoscopies with biopsies should be performed, especially in patients with pancolitis.
  • Such surveillance is recommended to start about 10 years after onset of the disease and repeated at 1- to 2-year intervals.
  • No evidence currently supports the need for cancer surveillance in patients with CD.
• Extraintestinal complications occur in approximately 25% of patients with IBD.³
• Arthritis - Peripheral arthritis, usually migratory and monoarticular, tends to parallel disease activity but may antedate it; ankylosing spondylitis, associated with HLA-B27
• Ocular complications can be divided into 3 groups. Primary complications are associated with the activity of the IBD, which occur with high frequency and respond to systemic therapy (systemic corticosteroids or surgical excision). Secondary complications result from another complication of CD. Coincidental complications are not true complications but conditions that occur so frequently in healthy people that they are not considered directly related to IBD.
  • Primary complications include specific epithelial and anterior stromal keratopathy, limbal corneal infiltrates, subconjunctival hemorrhage, episcleritis, scleritis, acute iritis, chronic iridocyclitis, macular edema, retinal vasculitis, and papillitis.
    • Orbital inflammation can produce proptosis, pain, and limited movement from either myositis or general inflammation.
    • Optic neuritis can cause loss of vision in one or both eyes or by chiasmal involvement.
    • Episcleritis presents with burning eyes and scleral injection and is the most common ocular complication of CD; therefore, it is both a diagnostic point in differentiating CD from UC and a marker of the activity of the basic disease.
    • Iritis presents as an acute painful red eye with photophobia and conjunctival injection. It often runs a course independent of the intestinal disease.
  • Secondary complications may include night blindness and dry eyes as a result of vitamin A deficiency from decreased ingestion of vegetables (that irritate the gut) and malabsorption from disease or absence of the distal ileum.
    • Refraction changes occur with starting or stopping systemic corticosteroids. Cataracts also occur with chronic steroid use or chronic iridocyclitis.
    • Exudative retinal detachment, posterior scleritis, and optic disc edema have been reported.
    • Scleromalacia from scleritis and Candida endophthalmitis from intravenous nutrition also have been reported.
  • Coincidental complications include conjunctivitis, recurrent corneal erosion, glaucoma, and generalized retinal artery narrowing.
• Dermatologic
  • Erythema nodosum: This is characterized by painful, tender, raised, red or violaceous subcutaneous nodules, usually found over the extensor aspects of the arms and legs, especially the anterior tibia. Its activity usually follows that of the intestinal disease and often heralds onset of increased bowel activity.
  • Pyoderma gangrenosum: Ulcerating, relatively painless lesions, hypothesized to be caused by an abnormal T-cell and neutrophil response,⁴ and correlate with bowel activity in about 50% of patients. Although the ulcers may exhibit purulent drainage, culture is sterile. Aphthous ulcers also are more common in patients with IBD.
• Other
  • Additional extraintestinal manifestations include liver disease, including pericholangitis, chronic active hepatitis, cirrhosis, primary sclerosing cholangitis, and bile duct carcinoma.
  • Gallstones occur in about one third of patients with CD, a result from increased lithogenicity of the bile due to impaired ileal absorption of bile acids.
  • A hypercoagulable state can occur, leading to deep venous thromboses, pulmonary embolism, and arterial thromboses.

Prognosis

• Ulcerative colitis  
  • In UC, a small percentage of patients have a single attack and no recurrence. However, remissions and exacerbations typically occur, with acute attacks lasting weeks to months.
  • Twenty percent of patients require colectomy, which is curative.
  • Long-term morbidity results primarily from complications of medical therapy, especially chronic steroids.
• Crohn disease 
  • Prognosis in patients with CD depends on the site and the extent of disease.
  • Periodic remissions and exacerbations are the rule.
  • About 50% of patients require surgical intervention; 50% of those undergoing surgery require a second operation, and of these, 50% have a third operation.
  • The recurrence rate is 25-50% within 1 year for patients who have responded to medical management and is higher for those who require surgery.
  • Overall, the quality of life with CD generally is lower than with UC, and death usually occurs as a consequence of surgery, pulmonary embolus, or sepsis.
  • Because patients with CD survive longer, intestinal cancer may become a more important long-term complication.

Patient Education

• For excellent patient education resources, visit eMedicine's Crohn Disease Center and Esophagus, Stomach, and Intestine Center. Also, see eMedicine's patient education articles Inflammatory Bowel Disease, Crohn Disease, Crohn Disease FAQs, and Irritable Bowel Syndrome.

Miscellaneous

Medicolegal Pitfalls

• Failure to obtain early surgical consultation for suspected obstruction, peritonitis, or fulminant disease
• Failure to consider diagnosis of IBD, especially CD, in patients presenting with perianal disease
• Unusual presentations, such as sciatica resulting from a terminal ileal abscess with right iliopsoas extension
• Steroids may mask the clinical severity of illness. Be especially suspicious of the febrile patient on steroids, who may be harboring a serious bacterial infection or abscess.
• Failure to consider concomitant enteric infection as the cause of an exacerbation
• Avoid use of antidiarrheals, anticholinergics, and narcotics in fulminant disease.

Special Concerns

• Pediatrics  
  • About 15-30% of patients with IBD present before age 20 years. Their presentation can include growth failure from malnutrition and delayed sexual maturation.
  • Sulfasalazine may be used as in adults, but steroids should be administered on an alternate day regimen, if possible, to diminish side effects.
  • Although immunosuppressives have been used in children, there is even more concern over adverse reactions, including possibility of malignancy in view of the potential for longer exposure.
• Pregnancy
  • Generally, outlook is good; however, IBD has been associated with an increased frequency of adverse pregnancy outcomes.
  • About 50% of those patients with inactive colitis develop an exacerbation.
  • Sulfasalazine and steroids may be administered during pregnancy

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Keywords

Crohn disease, Crohn's disease, CD, IBD, ulcerative colitis, UC, regional enteritis, terminal ileitis, granulomatous ileocolitis, chronic inflammatory diseases, gastrointestinal tract, GI tract, irritable bowel syndrome, IBS

Contributor Information and Disclosures

Author

Mounir Bashour, MD, CM, FRCS(C), PhD, FACS, Assistant Professor of Ophthalmology, McGill University; Clinical Assistant Professor of Ophthalmology, Sherbrooke University; Medical Director, Cornea Laser and Lasik MD
Mounir Bashour, MD, CM, FRCS(C), PhD, FACS is a member of the following medical societies: American Academy of Ophthalmology, American Association for Pediatric Ophthalmology and Strabismus, American College of International Physicians, American College of Surgeons, American Medical Association, American Society of Cataract and Refractive Surgery, American Society of Mechanical Engineers, American Society of Ophthalmic Plastic and Reconstructive Surgery, Biomedical Engineering Society, Canadian Medical Association, Canadian Ophthalmological Society, Contact Lens Association of Ophthalmologists, International College of Surgeons US Section, Ontario Medical Association, Quebec Medical Association, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Medical Editor

Andrew A Dahl, MD, Director of Ophthalmology Teaching, Mid-Hudson Family Practice Institute, The Institute for Family Health; Assistant Professor of Surgery (Ophthalmology), New York College of Medicine
Andrew A Dahl, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Ophthalmology, American College of Surgeons, American Medical Association, American Society of Cataract and Refractive Surgery, and Wilderness Medical Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Simon K Law, MD, PharmD, Assistant Professor of Ophthalmology, Jules Stein Eye Institute; Chief of Section of Ophthalmology Surgical Services, Department of Veterans Affairs Healthcare Center, West Los Angeles
Simon K Law, MD, PharmD is a member of the following medical societies: American Academy of Ophthalmology, American Glaucoma Society, and Association for Research in Vision and Ophthalmology
Disclosure: Nothing to disclose.

Managing Editor

R Christopher Walton, MD, Professor, Director of Uveitis and Ocular Inflammatory Disease Service, Department of Ophthalmology, Assistant Dean for Graduate Medical Education, University of Tennessee College of Medicine; Consulting Staff, Regional Medical Center, Memphis Veterans Affairs Medical Center, St Jude Children's Research Hospital
R Christopher Walton, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Healthcare Executives, American Uveitis Society, Association for Research in Vision and Ophthalmology, and Retina Society
Disclosure: Nothing to disclose.

CME Editor

Lance L Brown, OD, MD, Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri
Disclosure: Nothing to disclose.

Chief Editor

Hampton Roy Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and Pan-American Association of Ophthalmology
Disclosure: Nothing to disclose.

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