Crohn Disease is an idiopathic, chronic, granulomatous inflammatory disease that can affect any part of the GI tract from the mouth to the anus. It is an incurable,slowly progressive disease characterized by episodes of exacerbation and remission. The incidence is 4/100,000, with a bimodal age distribution among those 15 to 29 and 55 to 70 years old.
The etiology of Crohn disease is unknown but is believed to involve interplay between genetic and environmental factors. Pathogenesis likely relates to a defective mucosal barrier and/or dysregulated intestinal immunity, which leads to a chronic inflammatory reaction within the intestinal wall. The genetic component is strong: Crohn disease is 25 times more common among patients with a family history and has a concordance rate of 60% in monozygotic twins. Environmental factors such as smoking increase the risk of developing Crohn disease.
The terminal ileum is the most common site involved (75% of patients). Three “patterns” of disease have been described.Ileocolic disease involves the terminal ileum (and in some cases the cecum) and is the most common form, affecting 40% of patients.
Small-bowel-only disease (30% of patients) is confined to the more-proximal small intestine.
Colonic disease (30% of patients) affects only the large intestine. Perianal Crohn disease commonly coexists with these more proximal forms of the disease, especially when the colon is involved. Disease confined to the anorectum is rare (5%).
Grossly, diseased bowel is thickened, displays creeping fat and corkscrew vessels, and has a shortened fibrotic mesentery containing enlarged lymph nodes. The mucosal lesions include pinpoint hemorrhages, aphthous ulcers, deep linear fissures, and, ultimately, cobblestoning. It is common for these lesions to occur segmentally along the intestine rather than being contiguous.
Crohn disease is characterized by full-thickness, transmural inflammation of the bowel wall. The inflammation begins adjacent to the crypts, leading to the development of crypt abscesses, aphthous ulcers, and linear fissures. The transmural involvement can produce sinus tracts and fistulas between crypt abscesses and adjacent segments of bowel.
Granulomas are found in the bowel wall in 40% to 60% of patients, and they are detected in mesenteric lymph nodes in 25% of patients.
Clinical presentation of Crohn disease is highly variable. Patient history is important in narrowing the differential diagnosis. Physical examination is performed with special attention to the abdominal and anorectal areas. No physical signs are pathognomonic for Crohn disease, although the appearance of the perianal area described earlier is highly suggestive. Laboratory evaluation is nonspecific.
Diarrhea occurs in almost all patients and usually is not bloody unless the colon is involved. Patients with ileal disease may be bile salt deficient, resulting in steatorrhea. Mucosal inflammation with decreased absorption and increased secretion also results in diarrhea.
Abdominal pain typically is intermittent, crampy, worse after meals, relieved by defecation, and poorly localized. A mass caused by thickened bowel, a phlegmon, or an abscess may be palpable.
Weight loss occurs as a result of decreased oral intake, malabsorption, protein-losing enteropathy, and steatorrhea. Children with Crohn disease develop vitamin and mineral deficiencies and growth retardation.
Constitutional symptoms such as malaise and fever are common.
Anorectal disease is a common finding and may precede intestinal symptoms by several years. Such lesions include recurrent nonhealing anal fissures, large ulcers, complex anal fistulas, perianal abscesses, large, fleshy tags, and bluish skin discoloration. They are characterized by a multiplicity of lesions, lateral fissures, deep ulcers of the perianal skin and anal canal, and anal stricture.
Extraintestinal manifestations are numerous. The eyes may develop conjunctivitis, iritis, and uveitis. The skin may develop pyoderma gangrenosum, erythema nodosum multiforme, and aphthous stomatitis. Musculoskeletal manifestations include arthritis, ankylosing spondylitis, and hypertrophic osteoarthropathy. Finally, sclerosing cholangitis can lead to cirrhosis and liver failure.
Imaging studies are indicated when establishing the diagnosis of Crohn disease or when a complication develops that requires surgical intervention.
Contrast radiographs, which include small-bowel follow-through, enteroclysis, and water-soluble contrast enema, are very valuable in the diagnosis of Crohn disease. These studies usually reveal strictures or segments of ulcerated mucosa.
Endoscopy is most useful for obtaining biopsy material in patients with terminal ileal and colonic disease. As in patients with ulcerative colitis, those with long-standing (>10 years) Crohn colitis are at increased risk for adenocarcinoma, and colonoscopy is important for cancer surveillance. These patients also have an increased incidence of small-bowel cancer.
CT is useful for identifying abscesses, focal inflammation, and wall thickening. Abscesses can be drained percutaneously under CT guidance.
Complications include intestinal obstruction, stricture, fistula, perforation, intra-abdominal abscess, gastrointestinal bleeding, and perirectal abscess and fistula. Toxic colitis is a surgical emergency that can occur in these patients.
Differential diagnosis of Crohn disease includes other inflammatory bowel diseases, as well as common infectious abdominal conditions.
Ulcerative colitis. Patients with Crohn disease generally have less severe diarrhea, usually without gross blood. Perianal lesions, nonconfluent skip lesions, transmural involvement, large mucosal ulcers and fissures, involvement of small intestine, rectal sparing, and the presence of granulomas all help to differentiate Crohn disease from ulcerative colitis. Some patients who cannot be confidently diagnosed with either condition are labeled as having indeterminate colitis.
Appendicitis. Acute right-lower-quadrant abdominal pain due to Crohn ileitis can mimic acute appendicitis.
Infectious ileitis presents with pain and bloody diarrhea. The diagnosis is made by stool culture.
Other diseases that present similarly to Crohn disease include intestinal lymphoma, intestinal tuberculosis, ischemic enteritis, diverticulitis, pseudomembranous colitis, and irritable bowel syndrome.
Treatment
Adequate nutrition is essential both during and between disease flares, and enteral feeds should be continued whenever possible. A low-residue, high-protein, milk-free diet generally provides adequate nutrition. Vitamin and mineral supplementation may be necessary. Patients with severe or unresponsive disease should be started on TPN and placed on complete bowel rest.
Medical management is particularly important because Crohn disease has no cure. Therefore, treatment seeks to palliate symptoms, reduce bowel inflammation, and correct nutritional disturbances. Therapeutic recommendations depend on the disease location, severity, and complications. Mild to moderate disease can be treated with an oral aminosalicylates (sulfasalazine 3 to 6 g/day, or mesalamine 1 g four times a day). For ileal, colonic, or perianal disease, metronidazole, 500 mg three times a day, can be added. In patients with severe disease, steroid therapy should be initiated after active infection or abscess has been excluded. Prednisone, with initial daily doses of 40 to 60 mg orally, is a common outpatient treatment for acute flares; inpatients may receive hydrocortisone, 50 to 100 mg intravenously every 6 hours. Response to therapy should become evident within 7 days. Data have shown that infusions of infliximab (Remicade), a monoclonal antibody against tumor necrosis factor, is effective for Crohn flares and even Crohn fistulas (N Engl J Med 2004;350:876). Before receiving infliximab, the patient must have no active source of infection and be purified protein derivative (PPD)-negative. Infliximab is of particular use in poor surgical candidates who have otherwise failed medical management. After a patient has recovered from an acute flare, the medical regimen should be simplified to prevent long-term complications. In particular, steroids should be tapered as soon as possible to prevent side effects such as osteopenia, avascular necrosis, psychosis, and weight gain. The addition of immunomodulators, such as 6-mercaptopurine, may allow patients with refractory disease to taper off of prednisone.
Surgical therapy is indicated for failure of medical therapy or to address acute complications of the disease, such as high-output fistulas, perforation, intra-abdominal abscess, severe colitis, bleeding, or obstruction from fibrotic strictures. Abdominal abscesses can usually be drained percutaneously with elective bowel resection thereafter. Most Crohn patients require operative treatment at some point in their life.
At the time of operation, the most important principle is to correct the complication while preserving bowel length to prevent short-gut syndrome. Resection to histologically negative margins does not significantly reduce the likelihood of disease recurrence; therefore, grossly normal margins of 2 cm are accepted. In the absence of free perforation, large abscesses, massively dilated bowel, severe malnutrition, or high-dose immunosuppression, primary anastomosis is safe. Stapling should be avoided in thick-walled bowel; in this situation, a hand-sewn anastomosis is indicated. Recent series suggest that laparoscopic ileocolic resections are safe alternatives to open procedures, especially at the time of first operation (Dis Colon Rectum 2003;46:1129). Issues that require special consideration beyond the scope of this chapter are duodenal disease, multiple skip lesions, and chronic fibrotic strictures in the setting of short-bowel syndrome.
Appendectomy. Patients who are being explored for presumed acute appendicitis and are found to have Crohn ileitis should have the appendix removed if the cecum is not inflamed. Conventional teaching has been that the terminal ileum should not be removed. This is controversial, however, given the low morbidity of ileocecal resection and the uncertainty of response to subsequent medical therapy.
Surgical complications include anastomotic leaks, enterocutaneous fistulas, and sepsis related to intra-abdominal abscesses and wound infections.
Prognosis. Crohn disease is a chronic panintestinal disease that currently has no cure. It requires chronic, lifelong treatment, with operation reserved for severe complications. Recently, however, specific “susceptibility genes” (NOD2/CARD15) have been identified in patients with Crohn disease. Further study of the pathways involved may shed light on pathogenesis and lead to more effective medical treatments.