 |
Crohn's 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 arise. Extraintestinal
symptoms, particularly arthritis, may occur. Diagnosis
is by colonoscopy and barium contrast 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
Crohn's 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's 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's 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 (“skip areas”); hence, the name regional enteritis. About 35% of Crohn's 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; and 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.
Symptoms and Signs
The most common initial presentation 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 also may produce bowel obstruction, which begins rapidly, without the prodrome of fever, pain, and malaise typical of obstruction due to a Crohn's 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 produces a variety of systemic symptoms, including fever, weight loss, malnutrition, and extraintestinal manifestations (see Inflammatory Bowel Disease (IBD)).
The “Vienna Classification” and its recent “Montreal modification” categorize Crohn's disease into three principal patterns: (1) primarily inflammatory, which after several years commonly evolves into either (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
Crohn's 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's disease also increases the index of suspicion. Similar signs and symptoms (eg, abdominal pain, diarrhea) may be produced by other GI disorders. Differentiation from UC (see Table 1: Inflammatory Bowel Disease (IBD): Differentiating Crohn's Disease and Ulcerative Colitis ) may be an issue in the 20% of cases in which Crohn's 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 on relapse) should have flat and upright abdominal x‑rays and an abdominal CT scan. These studies demonstrate obstruction, abscesses or fistulas, and other possible causes of an acute abdomen (eg, appendicitis). Ultrasound 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 enterography, which combines high-resolution CT 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 appear 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, lymphosarcoma, 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 obtained to screen for anemia, hypoalbuminemia, and electrolyte abnormalities. Liver function tests should be obtained; 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.
Perinuclear antineutrophil cytoplasmic antibodies are present in 60 to 70% of patients with UC and in only 5 to 20% of patients with Crohn's disease. Anti-Saccharomyces cerevisiae antibodies are relatively specific for Crohn's disease. However, these tests do not reliably separate the two diseases. They have uncertain value in cases of “indeterminate colitis” and are not recommended for routine diagnosis.
Prognosis
Established Crohn's disease is rarely cured but is characterized by intermittent exacerbations and remissions. Some patients suffer 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's disease-related mortality.
Treatment
Details of specific drugs and dosages are discussed above (see Inflammatory Bowel Disease (IBD): Treatment).
General
management:
Cramps and diarrhea may be relieved by oral administration of loperamide 2 to 4 mg or antispasmodic drugs up to 4 times a day (ideally before meals). Such symptomatic treatment is safe, except in cases of severe, acute Crohn's 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‑Aminosalicylic acid (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's 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 . Infliximab is preferred by some as a second-line agent after corticosteroids, and even as a first-line agent in preference to corticosteroids, but it is contraindicated in active uncontrolled infection.
Obstruction is managed initially with nasogastric suction and IV fluids. Obstruction due to uncomplicated Crohn's 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 administered 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:
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 for more rapid response. 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 rather than a primary treatment.
Maintenance
therapy:
Patients who re quire only 5-ASA or an antibiotic to achieve remission can be maintained on this drug. Patients requiring acute treatment with corticosteroids or infliximab generally require azathioprine , 6‑ mercaptopurine , or methotrexate for maintenance. Systemically active corticosteroids are neither safe nor effective for long-term maintenance, although budesonide has been shown to delay relapse with fewer side effects. Patients who respond to infliximab for acute disease but who are not well maintained on antimetabolites may stay in remission with repeat doses of infliximab 5 to 10 mg/kg at 8‑wk intervals. Monitoring during remission can be done by following symptoms and blood tests and does not require routine x‑rays or colonoscopy (other than regular surveillance for dysplasia after 7 to 8 yr of disease).
Surgery:
Even though about 70% of patients ultimately require an operation, surgery is always performed 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 and > 85% at 3 yr; defined by clinical symptoms, it is about 25 to 30% at 3 yr and 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 , metronidazole , or possibly 5‑ASA. Moreover, when surgery is performed for appropriate indications, almost all patients experience an improved quality of life.
Last full review/revision January 2007 by David B. Sachar, MD; Aaron E. Walfish, MD
Content last modified January 2007
| |
