GRANULOMATOUS COLITIS

GRANULOMATOUS COLITIS

• Granulomatous colitis (Crohn's disease, CD, of the colon) is also an inflammatory disease of the large bowel of unknown cause.
• It is well accepted that CD of the large and small intestine is one disease, but it is separate and distinct from UC.
• CD is more common in Jews, uncommon in blacks, and more frequent in populations of Westernized civilizations than those of Africans and Asians.
• The disease primarily affects young individuals, with 80% of cases occurring in patients younger than 35 years.
• Disease in which the colon is primarily involved affects women slightly more often than men and occurs at a somewhat older age.
• The colon may be involved with granulomatous disease in one of several ways.
• First, the colon alone may be the site of the primary granulomatous disease.
• The large bowel may be involved in its entirety, but more often there is segmental disease with sparing of the rectum and part of the sigmoid.
• In addition to granulomatous disease of the colon, there may be involvement of the small bowel.
• This form of ileocolitis is the most common type of CD.
• The colon may become involved with granulomatous disease only after surgery for regional ileitis, but this is not particularly common, because most recurrences appear at the site of or proximal to the anastomosis.
• Finally, the colon may be involved indirectly via fistula formation from a loop of small bowel that is the site of the primary disease.
• In this case, most commonly there is no primary disease in the colon but only secondary inflammation from the disease in the small intestine.

Pathologic Features

• Granulomatous colitis involves all layers of the bowel wall as a transmural reaction.
• This transmural reaction may be noted grossly but is present in the early phases of the disease when only microscopic changes are noted.

Crohn's disease of the colon.

• Transmural involvement is present with mucosal ulceration (U),
• edema of the entire bowel wall and
• serosal noncaseating granuloma.

Although the gross and microscopic features of CD are well established, there is no pathognomonic feature.

The features of UC and CD are-

• In approximately 10 to 15% of patients, it may be difficult to equivocally differentiate CD from UC.
• The term indeterminate colitis has been used in these cases in which a definitive pathologic diagnosis cannot be made.

Characteristics of Crohn's Colitis and Ulcerative Colitis
Feature
Crohn's Colitis Ulcerative Colitis
Thickened bowel wall + + + +
Narrowing of bowel lumen + + + +
Discontinuous disease + + ○
Rectal involvement ○ + + +
Deep fissures and fistulas + + ○
Confluent linear ulcers + + ○
Perianal disease + + ○
Microscopic
Transmural inflammation + + + +
Submucosal infiltration + + + +
Submucosal thickening, fibrosis + + + ○
Ulceration through mucosa + + + + +
Fissures + + + +
Granulomas + + ○
Features are characterized as being present consistently (+ + +), frequently (+ +), infrequently (+), or rarely (○).

On macroscopic examination

• the bowel wall appears to be thickened, particularly in the submucosal layer.
• Correspondingly, there is narrowing of the lumen.
• Edema, thickening, and overgrowth of the mesenteric fat encroaching on the serosal aspect of the bowel wall are the rule with granulomatous disease of both the small and large intestine.
• The serosa tends to be hyperemic with visible vessel engorgement, and there are chronic subserosal inflammatory changes with exudate production.
• Mesenteric lymph nodes may be enlarged.

The gross appearance of the mucosal surface varies depending on the extent and severity of the disease.

• The mucosa may appear to be normal except for hyperemia and edema, or there may be longitudinal ulcers that cause the mucosal surface to have a cobblestone appearance.
• The ulcers vary in depth but usually extend at least to the submucosa and often to the serosa.
• Because of this, frequently other loops of intestine adhere to the involved segment, and fistulas may occur.

In addition, skip areas may be seen.

Microscopic changes include

• infiltration of inflammatory cells in all layers and
• marked submucosal and subserosal thickening and
• intramural fissures that can extend through to the mesenteric fat.
  

Criteria for the histologic diagnosis of granulomatous colitis have been classified as major and minor.
The major criteria are
(1) giant cells or epithelioid granulomas that occur either intramurally or within regional lymph nodes
(2) intramural fissures or fistulas,
(3) transmural mononuclear inflammation, and
(4) transmural fibrosis.
The minor criteria are
(1) submucosal lymphangiectasia,
(2) chronic serositis when there has been no prior surgery,
(3) muscle wall thickening (more than twice that of normal), and
(4) segmental involvement.

Clinical Features
Symptoms of granulomatous colitis include

• diarrhea,
• mid-abdominal and lower abdominal crampy pain,
• malaise, and
• weight loss.

Other symptoms and clinical findings include

• fever,
• rectal bleeding,
• anemia,
• nausea, and vomiting.

Occasionally, patients may present with symptoms suggestive of an acute abdomen.

It is now recognized that toxic megacolon can complicate Crohn's colitis as well as other forms of colitis.
Extraintestinal manifestations are common, with musculoskeletal manifestations being the most frequent.
Clinically, granulomatous colitis often has an extremely variable onset and course.

• Although diarrhea is a dominant feature of both UC and granulomatous colitis,
• colonic bleeding is less common with granulomatous disease.
• However, massive bleeding from acute granulomatous colitis can occur on occasion.
• Colonic sinuses, fistulas, and strictures are characteristic of granulomatous colitis.
• However, these internal complications do not occur as frequently in colon disease as they do in terminal ileum disease.

Perianal disease is a frequent complication.
· It is an extremely troublesome problem and difficult to treat successfully.
· In the National Cooperative Crohn's Disease Study,

• more than 46% of patients with colon disease had associated perianal lesions,
• whereas the rate was 25% in those with disease localized to the small bowel.
• The perianal lesions can precede the clinical appearance of the colitis by a variable number of years.
• Buchmann and Alexander-Williams classified perianal disease into the following categories: skin lesions, anal canal lesions, fistulas, and hemorrhoids.

Skin lesions include

• maceration,
• erosion,
• ulceration,
• abscess formation,
• and skin tags.

Because of the frequency of diarrhea in this disease, the skin around the anus may become macerated, leading to ulceration and subcutaneous abscess formation.

• Skin tags are frequent manifestations.
• They tend to be edematous and larger, thicker, and harder than those seen in patients without CD.

Anal canal lesions include

• fissures,
• ulcers, and
• stenosis of the anal canal.
  o The fissures tend to be deep and wide, with undermined edges.
  o Particularly important is the fact that they may be eccentrically placed in any position around the anus, in contradistinction to the uncomplicated fissure in patients who do not have CD.
• The fissures in these patients usually lie in the midline; unless there is associated sepsis, they tend to be painless.

Fistulas and abscesses

• are perhaps the most difficult of the perianal lesions.
• They may arise from an infected anal gland, as in patients without CD.
• However, more commonly they result from penetration by anal canal or rectal fissures or ulcers.
• On occasion, these fistulas are low lying and can be treated in a conventional manner.
• The more complex fistulas, however, may have a high internal opening with multiple indirect tracks opening on the buttocks or scrotum.
• Some of these tracks may communicate with each other.
• The fistulas tend to be chronic, indurated, and cyanotic, but despite their appearance, they are often painless.
• If the patient does complain of pain, one should suspect an abscess.

Rectovaginal fistulas can also complicate CD and tend to result from direct penetration of rectal wall fissures into the vagina.

• They are a relatively frequent complication of severe perianal disease, with rates varying from 3.5 to 20%.
• Quite frequently, these fistulas are asymptomatic, and no surgical intervention should be attempted.
• However, if the patient is symptomatic, surgery is indicated.
• Various local procedures have been described, but none are extremely successful.
• Some patients will require proctectomy

Diagnosis of Granulomatous Colitis

• Endoscopic evaluation of the colon and rectum is essential.
• Colonoscopy is particularly important to determine the extent of the disease and,
• in our opinion, is a more sensitive test than radiologic examination.
• For gross features of the disease, endoscopy and radiology might be equivalent.
• However, for the detection of early manifestation of the disease such as superficial ulcers, colonoscopy is superior.
• In addition, the discontinuous nature of the disease can be seen better with the colonoscope than on radiologic examination.
• It is our routine practice for all patients who undergo surgery for CD, including those with CD of the small bowel, to undergo a total colon examination before surgery to fully determine the extent of the disease.

The endoscopic appearance of Crohn's colitis is quite different from that of UC.

• The rectum is spared in approximately 50% of patients with large bowel involvement.
• Depending on the extent and severity of the disease,
• there may be isolated aphthous ulcers with normal intervening mucosa,
• or there may be
• irregular mucosal thickening,
• congestion,
• edema, and
• a cobblestone appearance with
• deep linear ulcerations and fistulas.
• Pathognomonic features of CD (i.e., granulomas) are present in only 20 to 40% of cases.

Radiologic features characteristic of Crohn's colitis are similar to those seen in terminal ileum disease.
The radiologic features that substantiate the diagnosis of Crohn's colitis include

• skip areas,
• longitudinal ulcerations,
• transverse fissures,
• eccentric involvement,
• pseudodiverticula,
• narrowing,
• strictures,
• pseudopolypoid changes,
• a cobblestone pattern,
• internal fistulas,
• sinus tracks,
• and intramural fistulas that extend parallel to the lumen of the thickened bowel.

Any portion of the colon may be involved with Crohn's colitis.

• The segments most frequently involved are the
• transverse colon,
• the cecum, and
• the ascending colon.
• The segment least frequently involved is the rectum.
• The skip areas must be sought carefully,
  o because discontinuous involvement may be limited to one wall,
  o may appear as a nodular filling defect,
  o or may involve straightening and rigidity of a short segment of the colon.

The combination of longitudinal ulcers, edematous mucosa, and transverse linear ulcers produces the cobblestone pattern previously described.

• Transverse linear ulcers may penetrate so deeply into the wall of the colon that they appear in contour as numerous long, thin spicules perpendicular to the long axis of the bowel or as a sinus track.
• They may ultimately lead to small intramural abscesses or fistulas.
• A small bowel enema or enteroclysis should be included as part of the workup in patients with Crohn's colitis to document the total extent of the disease.

Granulomatous Colitis and Carcinoma
Granulomatous ileocolitis has been recognized as a condition predisposing to the development of colorectal carcinoma.
The risk of developing carcinoma in CD is not as well defined as in UC, but some sources quote up to a 20-fold increase in gastrointestinal malignancy in patients with CD.
Carcinoma may also occur in chronic perianal fistulas.
A dilemma arises concerning the association of granulomatous colitis and carcinoma when one considers patient follow-up.
Although the incidence of cancer in Crohn's colitis is increased, it is still unclear how frequently these patients should be followed with either colonoscopy, radiology, or a combination of both.
Our recommendations for patients with Crohn's colitis are similar to those for patients with chronic UC (see earlier).