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Crohn Disease

(Crohn's Disease; Regional Enteritis; Granulomatous Ileitis or Ileocolitis)

by Aaron E. Walfish, MD, David B. Sachar, MD

Crohn disease is a chronic transmural inflammatory disease that usually affects the distal ileum and colon but may occur in any part of the GI tract.

  • Symptoms include diarrhea and abdominal pain; abscesses, internal and external fistulas, and bowel obstruction may occur, as may extraintestinal symptoms, particularly arthritis.

  • Diagnosis is by colonoscopy and imaging studies.

  • Treatment is with 5-aminosalicylic acid, corticosteroids, immunomodulators, anticytokines, antibiotics, and often surgery.

(See also the American College of Gastroenterology’s practice guidelines for management of Crohn’s disease in adults .)

Pathophysiology of Crohn Disease

Crohn disease begins with crypt inflammation and abscesses, which progress to tiny focal aphthoid ulcers. These mucosal lesions may develop into deep longitudinal and transverse ulcers with intervening mucosal edema, creating a characteristic cobblestoned appearance to the bowel.

Transmural spread of inflammation leads to lymphedema and thickening of the bowel wall and mesentery. Mesenteric fat typically extends onto the serosal surface of the bowel. Mesenteric lymph nodes often enlarge. Extensive inflammation may result in hypertrophy of the muscularis mucosae, fibrosis, and stricture formation, which can lead to bowel obstruction. Abscesses are common, and fistulas often penetrate into adjoining structures, including other loops of bowel, the bladder, or psoas muscle. Fistulas may even extend to the skin of the anterior abdomen or flanks. Independently of intra-abdominal disease activity, perianal fistulas and abscesses occur in 25 to 33% of cases; these complications are frequently the most troublesome aspects of Crohn disease.

Noncaseating granulomas can occur in lymph nodes, peritoneum, the liver, and all layers of the bowel wall. Although pathognomonic when present, granulomas are not detected in about half of patients with Crohn disease. The presence of granulomas does not seem to be related to the clinical course.

Segments of diseased bowel are sharply demarcated from adjacent normal bowel (called skip areas), hence the name regional enteritis.

  • About 35% of Crohn disease cases involve the ileum alone (ileitis).

  • About 45% involve the ileum and colon (ileocolitis), with a predilection for the right side of the colon.

  • About 20% involve the colon alone (granulomatous colitis), most of which, unlike ulcerative colitis (UC), spare the rectum.

Occasionally, the entire small bowel is involved (jejunoileitis). The stomach, duodenum, or esophagus is clinically involved only rarely, although microscopic evidence of disease is often detectable in the gastric antrum, especially in younger patients. In the absence of surgical intervention, the disease almost never extends into areas of small bowel that are not involved at first diagnosis.

There is an increased risk of cancer in affected small-bowel segments. Patients with colonic involvement have a long-term risk of colorectal cancer equal to that of UC, given the same extent and duration of disease.

Chronic malabsorption may cause nutritional deficiencies, particularly of vitamins D and B 12 .

Symptoms and Signs of Crohn Disease

The most common initial manifestation of Crohn disease is

  • Chronic diarrhea with abdominal pain, fever, anorexia, and weight loss

The abdomen is tender, and a mass or fullness may be palpable. Gross rectal bleeding is unusual except in isolated colonic disease, which may manifest similarly to UC. Some patients present with an acute abdomen that simulates acute appendicitis or intestinal obstruction. About 33% of patients have perianal disease (especially fissures and fistulas), which is sometimes the most prominent or even initial complaint.

In children, extraintestinal manifestations frequently predominate over GI symptoms; arthritis, FUO, anemia, or growth retardation may be a presenting symptom, whereas abdominal pain or diarrhea may be absent.

With recurrent disease, symptoms vary. Pain is most common and occurs with both simple recurrence and abscess formation. Patients with severe flare-up or abscess are likely to have marked tenderness, guarding, rebound, and a general toxic appearance. Stenotic segments may cause bowel obstruction, with colicky pain, distention, obstipation, and vomiting. Adhesions from previous surgery may also cause bowel obstruction, which begins rapidly, without the prodrome of fever, pain, and malaise typical of obstruction due to a Crohn disease flare-up. An enterovesical fistula may produce air bubbles in the urine (pneumaturia). Draining cutaneous fistulas may occur. Free perforation into the peritoneal cavity is unusual.

Chronic disease causes a variety of systemic symptoms, including fever, weight loss, undernutrition, and extraintestinal manifestations.

The Vienna Classification and its recent Montreal modification categorize Crohn disease into 3 principal patterns: (1) primarily inflammatory, which after several years commonly evolves into (2) primarily stenotic or obstructing or (3) primarily penetrating or fistulizing. These different clinical patterns dictate different therapeutic approaches. Some genetic studies suggest a molecular basis for this classification.

Diagnosis of Crohn Disease

  • Barium x-rays of the stomach, small bowel, and colons

  • Abdominal CT (conventional or CT enterography)

  • Sometimes magnetic resonance (MR) enterography, upper endoscopy, and/or colonoscopy

Crohn disease should be suspected in a patient with inflammatory or obstructive symptoms or in a patient without prominent GI symptoms but with perianal fistulas or abscesses or with otherwise unexplained arthritis, erythema nodosum, fever, anemia, or (in a child) stunted growth. A family history of Crohn disease also increases the index of suspicion.

Similar symptoms and signs (eg, abdominal pain, diarrhea) may be caused by other GI disorders. Differentiation from UC may be an issue in the 20% of cases in which Crohn disease is confined to the colon. However, because treatment is similar, this distinction is critical only when surgery or experimental therapy is contemplated.

Patients presenting with an acute abdomen (either initially or during a relapse) should have flat and upright abdominal x-rays and an abdominal CT scan. These studies may show obstruction, abscesses or fistulas, and other possible causes of an acute abdomen (eg, appendicitis). Ultrasonography may better delineate gynecologic pathology in women with lower abdominal and pelvic pain.

If initial presentation is less acute, an upper GI series with small-bowel follow-through and spot films of the terminal ileum is preferred over conventional CT. However, newer techniques of CT or MR enterography, which combine high-resolution CT or MR imaging with large volumes of ingested contrast, are becoming the procedures of choice in some centers. These imaging studies are virtually diagnostic if they show characteristic strictures or fistulas with accompanying separation of bowel loops. If findings are questionable, CT enteroclysis or video capsule enteroscopy may show superficial aphthous and linear ulcers. Barium enema x-ray may be used if symptoms seem predominantly colonic (eg, diarrhea) and may show reflux of barium into the terminal ileum with irregularity, nodularity, stiffness, wall thickening, and a narrowed lumen. Differential diagnoses in patients with similar x-ray findings include cancer of the cecum, ileal carcinoid, lymphoma, systemic vasculitis, radiation enteritis, ileocecal TB, and ameboma.

In atypical cases (eg, predominantly diarrhea, with minimal pain), evaluation is similar to suspected UC, with colonoscopy (including biopsy, sampling for enteric pathogens, and, when possible, visualization of the terminal ileum). Upper GI endoscopy may identify subtle gastroduodenal involvement even in the absence of upper GI symptoms.

Laboratory tests should be done to screen for anemia, hypoalbuminemia, and electrolyte abnormalities. Liver function tests should be done; elevated alkaline phosphatase and γ–glutamyl transpeptidase levels in patients with major colonic involvement suggest possible primary sclerosing cholangitis. Leukocytosis or increased levels of acute-phase reactants (eg, ESR, C-reactive protein) are nonspecific but may be used serially to monitor disease activity. To detect nutritional deficiencies, levels of vitamin D and B 12 should be checked every 1 to 2 yr. Additional laboratory measurements, such as levels of water-soluble vitamins (folic acid and niacin), fat-soluble vitamins (A, D, E and K), and minerals (zinc, selenium, and copper ) may be checked when deficiencies are suspected. All patients with inflammatory bowel disease (IBD), whether male or female, young or old, should have their bone mineral density monitored, usually by dual-energy x-ray absorptiometry (DXA) scan.

Perinuclear antineutrophil cytoplasmic antibodies are present in 60 to 70% of patients with UC and in only 5 to 20% of patients with Crohn disease. Anti– Saccharomyces cerevisiae antibodies are relatively specific for Crohn disease. However, these tests do not reliably separate the 2 diseases. They have uncertain value in cases of indeterminate colitis and are not recommended for routine diagnosis. Additional antibodies such as anti-OmpC and anti-CBir1 are now available, but the clinical value of these supplementary tests is uncertain.


Established Crohn disease is rarely cured but is characterized by intermittent exacerbations and remissions. Some patients have severe disease with frequent, debilitating periods of pain. However, with judicious medical therapy and, where appropriate, surgical therapy, most patients function well and adapt successfully.

Disease-related mortality is very low. GI cancer, including cancer of the colon and small bowel, is the leading cause of excess Crohn disease-related mortality.

Treatment of Crohn Disease

  • Loperamide or antispasmodics for symptom relief

  • 5-Aminosalicylic acid (5-ASA) or antibiotics

  • Other drugs depending on symptoms and severity

  • Sometimes surgery

Details of specific drugs and dosages are discussed in treatment of inflammatory bowel disease.

General management

Cramps and diarrhea may be relieved by oral administration of loperamide 2 to 4 mg or antispasmodic drugs up to 4 times/day (ideally before meals). Such symptomatic treatment is safe, except in cases of severe, acute Crohn colitis, which may progress to toxic megacolon as in UC.

Hydrophilic mucilloids (eg, methylcellulose or psyllium preparations) sometimes help prevent anal irritation by increasing stool firmness. Dietary roughage is to be avoided in stricturing disease or active colonic inflammation.

Mild to moderate disease

This category includes ambulatory patients who tolerate oral intake and have no signs of toxicity, tenderness, mass, or obstruction.

5-ASA (mesalamine) is commonly used as first-line treatment, although its benefits for small-bowel disease are modest at best. Pentasa is the most effective formulation for disease proximal to the terminal ileum; Asacol is effective in distal ileal disease. All formulations are roughly equivalent for Crohn colitis, although none of the newer preparations rival sulfasalazine for efficacy on a dose-for-dose basis.

Antibiotics are considered a first-line agent by some clinicians, or they may be reserved for patients not responding to 4 wk of 5-ASA; their use is strictly empiric. With any of these drugs, 8 to 16 wk of treatment may be required.

Responders should receive maintenance therapy.

Moderate to severe disease

Patients without fistulas or abscesses but with significant pain, tenderness, fever, or vomiting, or those who have not responded to treatment for mild disease, require corticosteroids, either oral or parenteral, depending on severity of symptoms and frequency of vomiting. Oral prednisone or prednisolone may act more rapidly and reliably than oral budesonide, but budesonide has somewhat fewer adverse effects and is considered the corticosteroid of choice in many centers, especially in Europe.

Patients not responding to corticosteroids, or those whose doses cannot be tapered, should receive azathioprine, 6-mercaptopurine, or possibly methotrexate. An anti-TNF agent (infliximab, adalimumab, or certolizumab pegol) is preferred by some as 2nd-line therapy after corticosteroids, and even as first-line therapy in preference to corticosteroids, but its use is contraindicated in active uncontrolled infection.

Obstruction is managed initially with nasogastric suction and IV fluids. Obstruction due to uncomplicated Crohn disease should resolve within a few days and therefore does not require parenteral nutrition; absence of prompt response indicates a complication or another etiology and demands immediate surgery.

Fulminant disease or abscess

Patients with toxic appearance, high fever, persistent vomiting, rebound, or a tender or palpable mass must be hospitalized for administration of IV fluids and antibiotics. Abscesses must be drained, either percutaneously or surgically. IV corticosteroids should be given only when infection has been ruled out or controlled. If there is no response to corticosteroids and antibiotics within 5 to 7 days, surgery is usually indicated.


Fistulas are treated initially with metronidazole and ciprofloxacin. Patients who do not respond in 3 to 4 wk may receive an immunomodulator (eg, azathioprine, 6-mercaptopurine), with or without an induction regimen of infliximab or adalimumab for more rapid response. Anti-TNF therapy (infliximab or adalimumab) can also be used alone. Cyclosporine is an alternative, but fistulas often relapse after treatment.

Severe refractory perianal fistulas may require temporary diverting colostomy but almost invariably recur after reconnection; hence, diversion is more appropriately considered a preparation for definitive surgery or at best an adjunct to infliximab or adalimumab rather than a primary treatment.

Maintenance therapy

Patients who require only 5-ASA or an antibiotic to achieve remission can be maintained on that drug. Patients requiring acute treatment with corticosteroids or anti-TNF agents typically require azathioprine, 6-mercaptopurine, methotrexate, or anti-TNF therapy for maintenance. Many if not most patients brought into remission with an anti-TNF will require escalation of the dose or shortening of the treatment intervals within a year or two. Systemically active corticosteroids are neither safe nor effective for long-term maintenance, although budesonide has been shown to delay relapse with fewer adverse effects. Patients who respond to anti-TNF therapy for acute disease but who are not well maintained on antimetabolites may stay in remission with repeat doses of anti-TNF agents.

Monitoring during remission can be done by following symptoms and doing blood tests and does not require routine x-rays or colonoscopy (other than regular surveillance for dysplasia after 7 to 8 yr of disease).


Even though about 70% of patients ultimately require an operation, surgery is often done reluctantly. It is best reserved for recurrent intestinal obstruction or intractable fistulas or abscesses. Resection of the involved bowel may ameliorate symptoms but does not cure the disease, which is likely to recur even after resection of all clinically apparent lesions. The recurrence rate, defined by endoscopic lesions at the anastomotic site, is

  • > 70% at 1 yr

  • > 85% at 3 yr

Defined by clinical symptoms, the recurrence rate is about

  • 25 to 30% at 3 yr

  • 40 to 50% at 5 yr

Ultimately, further surgery is required in nearly 50% of cases. However, recurrence rates seem to be reduced by early postoperative prophylaxis with 6-mercaptopurine or azathioprine, metronidazole, or infliximab. Moreover, when surgery is done for appropriate indications, almost all patients have improved quality of life.

Because smoking increases the risk of recurrence, especially in women, smoking cessation should be encouraged.

Key Points

  • Crohn disease affects the ileum and/or colon but spares the rectum (which is invariably affected in ulcerative colitis).

  • Intermittent areas of diseased bowel are sharply demarcated from adjacent normal bowel (called skip areas).

  • Symptoms primarily involve episodic diarrhea and abdominal pain; GI bleeding is rare.

  • Complications include abdominal abscesses and enterocutaneous fistulas.

  • Treat mild to moderate disease with 5­aminosalicylic acid and/or antibiotics (eg, metronidazole, ciprofloxacin, rifaximin).

  • Treat severe disease with corticosteroids and sometimes immunomodulators (eg, azathioprine) or anti-TNF agents (eg, infliximab, adalimumab).

  • About 70% of patients ultimately require an operation, typically for recurrent intestinal obstruction, intractable fistulas, or abscesses.

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