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Crohn's Disease

 

 

Related narratives: Crohn's Colon Carcinoma, Recurrent Crohn's Disease

Crohn's disease is a transmural inflammatory disease that can affect any part of the GI tract, but most commonly small and large bowel. Both small and large bowel are affected in 55% of cases, small bowel alone 30% of the time, and isolated Crohn's colitis is found in 15%. The majority of patients are young adults in their second and third decades, with a smaller peak arising in the 6th decade. The highest incidence is found in North America and northern Europe. Smokers have twice the incidence over non-smokers. There is a higher prevalence in eastern European (Ashkenazi) Jews and a strong familial link (13% in first degree relatives and 30% in sibs). There is no known cure at present and medical and surgical treatment are palliative. Patients who have onset of disease before age 20 and those with duration longer than 13 years have increased mortality vs. the general population.

The disease is characterized by segmental involvement with insidious onset as mucosal inflammation, progressing to submucosal inflammation, ulceration and ultimately transmural involvement. Characteristic non-caseating granulomas with Langerhans giant cells are found in the bowel wall or mesenteric lymph nodes in more advanced stages in 60-70% of cases. Grossly, the bowel wall becomes thickened, gray to purple, and the mesenteric fat encroaches partially around the circumference. Inflamed segments are often adherent to adjacent structures. Luminal narrowing results from a combination of wall thickening, edema during acute inflammatory exacerbations and ultimately rigid stricture from repeated bouts of damage and repair with fibrous scar tissue. Strictures appear as the characteristic string sign on contrast studies of the bowel. The mucosa of involved segments has a cobblestone appearance. Deep linear ulcers on the mesenteric side of the lumen burrow transmurally resulting in intramesenteric or inter-loop abscesses. When these abscesses break into adjacent structures by pressure necrosis or are drained externally, fistulas often remain after resolution of the abscess. Usually the organ secondarily involved does not have active Crohn's inflammation. Terminal ileitis, often presenting as apparent appendicitis is most often a self-limited disease that does not progress to full blown Crohn's. The ileum should not be resected, and the appendix should be removed if the base of the cecum is normal appearing to avoid future confusion of recurrent symptoms.

The etiology is unknown, and infectious, immunological and genetic factors are possible factors. Mycobacterium paratuberculosis has been found in affected bowel wall, but antibiotic therapy has not proven effective to date. Crohn's colitis must be differentiated from true infectious colitis due to campylobacter or Yesinia. Cytokines IL1, 2, 8 and tumor necrosis factor have been found to be elevated in Crohn's and are suspected to play a role. The strong familial association and the finding of increased chromosomal breaks and abnormalities in the centromeric region of chromosome 16 support the suspicion of genetic factors. Diet, smoking and psychological factors are probably of minor importance.

Symptoms are usually gradual in onset starting with intermittent colicy pain followed by diarrhea. Patients with Crohn's tend to have fewer bowel movements than ulcerative colitis (see ulcerative colitis discussion) and tend not to have mucous, pus or blood with the stool. One third of patients have low-grade fevers, and patients may experience weight loss, weakness and malaise. Early onset in pre-adolescents may cause growth retardation.

Extraintestinal manifestations in Crohn's are the same as those in ulcerative colitis. Skin manifestations, erythema nodosum and pyoderma gangrenosum are the most common. Uveitis, iritis, sclerosing cholangitis, arthritis, ankylosing spondylitis, amyloidosis may be temporally unrelated to the activity of the disease.

Complications of Crohn's include abscess, perianal disease, fistula, toxic megacolon, Intestinal obstruction, usually of the small bowel, ureteral obstruction, anemia, and cancer. About 25% of patients will develop an abscess. Abscess should be drained with CT guidance. Perianal/perineal disease occurs in 20-30% of cases, associated with rectal involvement. Management is conservative to try and avoid proctectomy. Fistulas occur in 30-40% of Crohn's patients, usually are the sequellae of a resolved abscess and most commonly originate from the ileum. They may be asymptomatic if between adjacent bowel loops and may not require treatment. Enterovesicle fistula requires surgical treatment because of urinary tract infection. Cutaneous fistulas, usually through surgical incisions, cause nutritional problems and skin excoriation and can be very difficult to manage. Toxic megacolon is a life-threating emergency that is initially treated with anti-inflammatory drugs, but if that fails to produce resolution within a short period, total abdominal colectomy must be performed before perforation occurs. Obstruction may be due to inflammation and edema, fibrous stricture or abscess. Edematous obstruction may resolve with anti-inflammatory medical treatment, but fibrous stricture usually requires surgery. Ureteral obstruction, usually on the right, is usually a result of retroperitoneal iliopsoas abscess secondary to ileal disease. Drainage of the abscess usually relieves the obstruction. Retroperitoneal fibrosis may require ureterolysis. Anemia may result from slow chronic blood loss. Major hemorrhage is rare in Crohn's. Cancer superimposed on Crohn's, usually involves the colon, but small bowel cancer incidence is significantly higher (12x) than sporadic cases. The incidence of cancer in Crohn's colitis is now recognized to be similar to cancer arising in ulcerative colitis. They have a similar pathogenesis, arising in flat areas of dysplasia rather than from adenomatous polyps. They tend to be discovered late in more advanced stages. Cancer is the leading cause of Crohn's related mortality.

Medical therapy of Crohn's consists of sulfasalazine, 5-aminosalacilic acid, metronidazole, corticosteroids, immunosuppressive agents, and more recently antimicrobials. Newer sulfa-like drugs like mesalamine allow the slow release of 5-ASA, the active ingredient, through the small bowel. Steroids should only be instituted after abscess is ruled out. Immunosupression with azothioprine, 6-mercaptopurine are effective but have significant toxicity (pancreatitis, hepatitis and bone marrow suppression). There are promising developments in immunomodulatory therapy with cytokines and anticytokines as well as monoclonal antibody to tumor necrosis factor alpha. Metronidazole, ciprofloxacin, tetracycline and ampicillin are also being used. The majority of patients respond to medical management through multiple flare-ups and surgery is reserved for intractability and complications.

Approximately three quarters of patients will have one operation after 20 years of disease. The great majority will have endoscopic evidence or recurrent disease within 5 years, however less than half will require a second operation. Ten percent will have more than two operations. Bypass, usually of ileocolic disease is no longer practiced unless the patient's physical condition or anatomic constraints make resection prohibitive. Unresolving obstruction is the most common indication for operation. The goal is to remove as little bowel as possible to avoid short bowel syndrome. Resection margins are only to grossly normal bowel. There is no attempt to obtain histologically normal margins. In the last several years stricturoplasty has been employed in an attempt to preserve bowel, using a Heineke Mikulicz type for short segments and a Finney type for longer than 10 cm. Segmental colon resection is performed if possible, and abdominal colectomy with Brooke ileostomy is the procedure of choice if the colon is extensively involved or dysplastic. Iliorectal anastomosis may be done if there is normal rectal compliance and normal sphincter tone, but the incidence of recurrence in the rectal segment is high. Isolated colonic disease may be hard to differentiate from ulcerative colitis, and subtotal colectomy leaves the option of a pouch procedure and ileoanal anastomosis. Pouches are contraindicated in Crohn's because of the high incidence of recurrence and complications. Occasionally colonic diversion may be necessary to aid healing of perineal disease. Last resort proctectomy is often complicated by delayed perineal wound healing.

References:

Evers BM, in Townsend: Sabiston Textbook of Surgery, 16th ed., Copyright 2001 W. B. Saunders Company, 888-895

Guy TS, et al, Crohn's Disease of the Colon, Surg. Clin NA, 81:1, Feb 2001.

Church JM, Molecular genetics and Crohn's disease, Surg. Clin NA, 81:1. Feb 2001.


This page was last modified on 6-Sep-2002.