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					Inflammatory Bowel Disease
Michael Wong, MD


Definition

Inflammatory bowel disease consists of ulcerative colitis and Crohn's disease. Ulcerative colitis is
an idiopathic disorder characterized by inflammation limited to the mucosal layer of the colon,
almost invariably involving the rectum and extending in a proximal and continuous fashion to
involve other portions of the colon. Crohn's disease is characterized by transmural rather than
superficial inflammation involving the entire bowel wall from mucosa to serosa. This transmural
inflammatory process gives rise to fibrosis and the obstructive clinical presentations which are
common and not seen often in ulcerative colitis. In addition, as part of the transmural
inflammatory process, sinus tracts burrow through and penetrate the serosa, giving rise to
microperforations and fistula, which are also part of the clinical picture of Crohn's disease. Unlike
ulcerative colitis, which is limited to the colon, Crohn's disease may involve the entire
gastrointestinal tract from mouth to perianal area. About 80% of patients have small bowel
involvement, usually in the distal ileum, with one third of patients having ileitis alone.
Approximately 50% of patients will have both ileal and colonic involvement, so-called ileocolitis;
and 20% will have disease limited to the colon. In those cases, about 50% of patients with Crohn's
colitis will have sparing of the rectum. A small percentage of patients will have predominance of
involvement in the mouth or gastroduodenal area. Lesser numbers will have involvement of the
esophagus and proximal small bowel.

Epidemiologic, Etiologic and Pathophysiologic Features

Although both diseases have a worldwide distribution, the incidence is highest in developed areas
including North America, northern Europe and, to a lesser extent, South Africa and Australia.
They tend to occur in northern areas of a given country. These disorders tend to be diseases of
younger people, with peak incidence occurring in the late teens and early 20s up to age 40.
Nonetheless, it should be recognized that both ulcerative colitis and Crohn's disease may occur for
the first time in older patients, and several studies have suggested a second peak of incidence for
both disorders in patients over the age of 60. In the older age group, it can be especially difficult
to distinguished inflammatory bowel disease from ischemic disease. The patients and greater in
Caucasians than blacks. But as with the geographic distributions these conditions spare no ethnic,
racial or socioeconomic group. There is a clear familial pattern of inflammatory bowel disease, in
that 10 to 25% of patients who develop either ulcerative colitis or Crohn's disease will have a
close relative who also has a form of inflammatory bowel disease; and there tends to be a strong
concordance for disease category, especially with regard to Crohn's disease. For Crohn's disease
there is evidence for concordance for age of onset, disease location and severity of the clinical
course. Despite the obvious genetic predisposition, the majority of patients will not have a close
relative with IBD, and the influence of genetic predisposition versus environmental factors
remains unclear.
Both of these disorders are idiopathic, with the etiology being unknown. As suggested above,
there is considerable research interest in identifying a specific gene or genes which might be at the
root, at least in a subgroup of patients. It is clear that perturbations of the immune system are
occurring, and whether these are at the primary basis for etiology or represent a response to an
inciting factor is not completely clear. Much attention for many years has focused on an infectious
etiology. Most of the recent interest has centered on an atypical mycobacterium which has been
isolated from the tissues of certain patients with Crohn's disease and for which there is variable
histopathologic evidence associating this tuberculosis-like organism with Crohn's disease. There is
recent data linking prior measles infection to an increased risk of developing Crohn's disease and
the possible induction of a small-vessel granulomatous vasculitis. From the distribution of the
disorders, it would appear as though environmental factors are important. One such factor which
has been uncovered is the relation of cigarette smoking to IBD. With regard to Crohn's disease,
smoking seems to exacerbate and may predispose to the disorder. On the other hand, with regard
to ulcerative colitis, cigarette smoking appears to be protective, and one of the highest groups at
risk for the development of ulcerative colitis are those individuals who have recently stopped
smoking.

With regard to the pathophysiology of inflammatory bowel disease, there is a large amount of
research focused in this area, but as yet no unifying hypothesis has been developed. Current
thinking suggest that there is disruption of the mucosal barrier, perhaps by a variety of external
influences including infectious agents, anti-inflammatory drugs and possibly certain reactions with
food. This disruption of the mucosal barrier along with possible genetically determined increased
gut permeability allows antigens related to food and to bacterial metabolic products to enter the
submucosa where there may be abnormal processing of these antigens leading to stimulation of
helper T-cells instead of the normal mechanism of stimulation of suppressor T-cells which leads to
physiologic tolerance. When this process goes awry and there is a stimulation of helper T-cells as
well as macrophages, a variety of inflammatory mediators including cytokines and tumor necrosis
factor are released causing an inflammatory process which then becomes chronic, leading to the
observed pathologic and clinical abnormalities seen in both ulcerative colitis and Crohn's disease.
This abnormal processing of antigens and the susceptibility of disruption of the mucosal barrier
may be under genetic influence.

Ulcerative Colitis - Clinical Features

Rectal bleeding is almost always present once ulcerative colitis is well developed, and, in addition,
mucous is frequently observed in the stool. Patients will often complain of tenesmus and have
diarrhea. However, if the disease is limited to the rectum, patients may present with constipation,
rather than diarrhea, associated with rectal bleeding. For the patient presenting with constipation
and rectal bleeding, there is a tendency to presume that the bleeding is hemorrhoidal and the
constipation reflects a functional disorder. However, if mucous is observed in the stool, and, in
particular, the patient experiences tenesmus, which is unusual in typical irritable bowel syndrome,
with hemorrhoidal bleeding, then the suspicion of underlying proctitis has to be great. Abdominal
cramping may be absent until the disease is extensive, at least above the distal colon. Additional
clinical clues which should be sought out from the history include the presence of arthralgias or
frank arthritis, which will be present in up to 10% of patients with ulcerative colitis. Skin lesions
including erythema nodosum and, less commonly, pyoderma gangrenosum occur in this disorder,
and both arthritis and erythema nodosum may precede by months or even years the onset of the
typical symptoms of ulcerative colitis. Episcleritis and uveitis can be seen in association with
ulcerative colitis. The family history as noted above should be obtained and if positive for IBD
then the index of suspicion that the patient may have inflammatory bowel disease has to be high.

The diagnosis is generally established by the sigmoidoscopic appearance of the colon coupled
with a typical history. In contrast to the normal appearing mucosa, with well demarcated
vessels and a shiny, pale appearance, the vascular markings in ulcerative colitis are lost due to
engorgement of the mucosa with an erythematous appearance. In addition, petechiae, exudate,
touch friability and frank hemorrhage may be present. The biopsy may be helpful in distinguishing
ulcerative colitis from an acute self-limited infectious process, in that in ulcerative colitis chronic
changes including branching of crypts and atrophy and loss of mucin in goblet cells will typically
be present. Since treatment is based upon the extent of severity of disease, it is helpful at the initial
presentation to document the extent of disease, since topical therapy will usually be used initially
for patients whose process is limited to the lower 30 to 40 cm. A full colonoscopy on presentation
is generally not warranted unless there is confusion about the underlying diagnosis. The findings
described above with regard to an abnormal appearing mucosa are not specific to ulcerative
colitis, and other entities including Crohn's disease, radiation colitis, ischemic colitis, a variety of
infectious processes and colitis related to drugs all have to be excluded. It is particularly important
on initial presentation and during major flare-ups to rule out an infectious etiology. Typically,
these include Salmonella. Shigella. Campylobacter as well as Aeromonas and E. coli 0157:H7.
Previous antibiotic therapy may cause Clostridium difficile colitis, which may mimic ulcerative
colitis, although gross rectal bleeding is not common in this disorder. Some feel that many flares
of ulcerative colitis are related to C, difficile infection even in the absence of recent antibiotic
exposure. In the immunocompromised patient, cytomegalovirus as well as Kaposi's sarcoma are
considerations, since they can mimic ulcerative colitis. With regard to drug-related colitis, the
most prominent factor is the use of non-steroidal anti-inflammatory drugs (NSAIDS) . There are a
number of patients in whom acute or subacute colitis is caused by NSAIDS, and these agents have
the potential of exacerbating known underlying inflammatory bowel disease. Other drugs which
may cause a clinical picture resembling IBD include retinoic acid (Accutane), gold therapy and
possibly oral contraceptive pills. The literature is sufficiently confused with regard to the effectors
of the Pill on IBD that it does not justify stopping the Pill in every woman who develops
inflammatory bowel disease. However, if the inflammatory bowel disease came on relatively soon
after the onset of taking the Pill and the disease does not respond relatively quickly to standard
therapy, then consideration should be given to stopping it.

Crohn's Disease

The clinical features of Crohn's disease share many similarities with ulcerative colitis, especially
when the colon is involved. It should be noted that although rectal bleeding is almost always
present with ulcerative colitis once it is well developed, it occurs in only about half of the patients
who have Crohn's disease involving the colon. Because of the obstructing tendency of Crohn's
disease related to the transmural inflammation, fibrosis and narrowing, it is more likely with
Crohn's disease that patients will complain of chronic abdominal pain often related to the
narrowing and partial obstruction. Unlike patients with ulcerative colitis, upwards of a third of
patients with Crohn's disease will have significant and symptomatic perineal disease including
fistula abscesses and fissures. Weight loss is a feature of even early Crohn's disease, largely
because patients feel better when food is avoided. Finally, Crohn's patients may manifest fever in
the absence of obvious infection or even obvious intestinal symptoms, and Crohn's disease is one
of the unusual causes of a fever of unknown origin. With regard to clinical clues, which may not
be forthcoming in the initial history, aphthous ulcers in the mouth are often prominent in Crohn's
disease, more so than in ulcerative coliris. Additional clues which are similar to those for
ulcerative colitis include joint pain, skin lesions, eye inflammation and, as noted, the family
history.

With regard to diagnostic evaluation, when Crohn's disease involves the colon, colonoscopy may
be necessary to establish the diagnosis, since commonly the rectum and sigmoid are spared and
therefore the flexible sigmoidoscopy may well be normal. Barium enema, of course, is an
alternative to colonoscopy, although mild early Crohn's disease may be subtle enough to escape
detection on barium enema. Endoscopic features of Crohn's disease involving the colon include
focal ulcerations adjacent to areas of normal appearing mucosa along with polypoid changes of
the mucosa giving it a cobblestone appearance. These features tend to distinguish it from
uicerative coliris, which, until it is advanced, tends not to give gross ulcerations and which causes
a diffuse area of involvement on any given endoscopic view. With regard to small bowel disease,
although on occasion the colonoscope will reach the distal ileum, more often the diagnosis is
made on the basis of a small bowel x-ray, with an irregular appearing ileum often with separation
of bowel loops. As the process becomes more advanced, the distal ileum narrows, creating a
"string sign", which is related partially to fibrosis and partially to edema and spasm. The biopsy in
Crohn's disease, unlike that in ulcerative coliris, can be specific in granulomas are present and
certain infections and foreign bodies are ruled out. However, the absence of granulomas on biopsy
does not exclude Crohn's disease, since they are present in only about 30% of specimens.

Distinguishing Crohn's coliris from ulcerative coliris is important. Although standard medical
therapies of these disorders are similar, this distinction becomes crucial if colectomy is needed.
Moreover, there are some differences with regard to therapy beyond the standard agents, and
therefore an attempt should be made to decide which of the two processes is present. The
following features will tend to distinguish Crohn's colitis from ulcerative colitis:
   - If the small bowel is involved, then ulcerative colitis is excluded.
   - In the remaining patients, if the rectum is spared, then, again, ulcerative colitis is excluded.
   - A small number of patients will then be left, in which case if bleeding is absent, the
diagnosis of Crohn's disease should strongly be suggested.
   - In the remaining patients, perianal disease, if present, will exclude ulcerative colitis.
   By this process, one is left with a small percentage of patients who have Crohn's disease that
resembles ulcerative colitis. To make this final distinction, consideration should be given to the
focality of lesions, the presence of fistula or granulomas.
   Ultimately, a small proportion of patients remains in whom the diagnosis of Crohn's disease
cannot be distinguished from ulcerative colitis. Such patients have features which may resemble
both disorders, and these patients are called indeterminant colitis.
Complications

Both Crohn's disease and ulcerative colitis are associated with a number of systemic
complications. These include eye involvement with uveitis and episcleritis; skin processes such as
erythema nodosum and pyoderma gangrenosum, peripheral arthritis which is usually monarticular
asymmetric involving the large joints more than the small with no synovial destruction and no
subcutaneous nodules and seronegativity, ankylosing spondylitis and, finally, involvement of the
biliary tree in which sclerosing cholangitis often with a rising alkaline phosphatase is the most
common disorder.

A major concern of both patients and physicians caring for the patient is the development of colon
cancer. Colon cancer is clearly increased in both ulcerative colitis and Crohn's disease. With
regard to ulcerative colitis, the incidence begins to go up seven to eight years after the onset of
disease, and the risk of acquiring colon cancer is related to both the duration of the disease as well
as its extent. As an example, an episode of panotitis 25 years earlier, even if the disease has been
relatively quiescent since then, puts the patient at a high risk for colon cancer. On the other
hand, if the disease has been limited to the lower 15 to 20 cm of colon, but has remained active
throughout a 25-year period, there is virtually no increased risk for colon cancer. With regard to
ulcerative colitis, there is now evidence that involvement of the left colon up to the splenic whose
disease extends beyond that point. But, as noted, patients with proctitis and distal colitis appear to
be at very little increased risk. Although a variety of studies have given different risk estimates, it
is generally agreed that the risk goes up about one half percent per year after years seven to eight
for patients who have had disease, at least up to the splenic flexure. The older patient who
develops inflammatory bowel disease, therefore, may be at less risk than the patient who develops
it at a young age, although the older patient may have an added risk just by virtue of age alone.

The risk of colon cancer appears to be about the same whether the patient has ulcerative colitis or
Crohn's disease, although carcinoma in Crohn's disease has been less well studied than in
ulcerative colitis. In Crohn's disease, about two thirds of colon cancers occur in obviously
diseased bowel, while only one third are located in clinically uninvolved bowel. This differs from
ulcerative colitis, where carcinoma seems to involve only areas of previously involved bowel.
Surveillance colonoscopy is based upon the concept that dysplasia is a predictor of the
development of colon cancer or a marker that the cancer is already present. Several prospective
studies have associated high-grade dysplasia, with a 30 to 50% chance of colon cancer being
present, but not detectable by colonoscopy. It is, therefore, recommended that patients with
ulcerative colitis whose disease has extended to the splenic flexure or beyond have a surveillance
colonoscopy every two years initially. After a duration of 15 years of disease, annual colonoscopy
is recommended. The finding of high-grade dysplasia is an indication for total colectomy. There is
increasing feeling that even low-grade dysplasia should be a consideration for total colectomy,
although that is not as universally accepted. With regard to Crohn's disease, a similar
recommendation is now being made, although there is less data upon which to base that
recommendation. Indeed, surveillance colonoscopy can be considered at the time of diagnosis of
Crohn's disease, since many patients may have had subclinical disease for a number of years, and,
therefore, it is difficult to know the true duration of the inflammatory process involving the colon.
The use of colonoscopic surveillance is controversial, since it has not been well proven that
surveillance colonoscopy really impacts on mortality, although there is a suggestion of its benefit
from two recent retrospective analyses.

Therapy

Anti-inflammatory Agents

Sulfasalazine has been shown in controlled trials to be effective in active ulcerative proctocolitis
regardless of the extent of disease. It is also efficacious in maintaining long-term remission of
ulcerative colitis. It has proven useful in Crohn's disease, but primarily when the colon is involved,
since controlled trials have not shown efficacy with ileitis alone. However, in the doses studied in
controlled trials, it has not been shown to be effective at maintaining remission in Crohn's disease
nor in preventing postoperative occurrence after resection and anastomosis. Adverse effects limit
the use of sulfasalazine, and these include dyspepsia, nausea and anorexia, which may at times be
avoided by either lowering the dose or employing the use of an enteric-coated preparation. For
mild allergic reactions such as rash and fever, it may be possible to desensitize the patient by
gradually introducing very low doses with progressive increase in dose. However, more severe
reactions such as hemolysis, agranulocytosis, male infertility, alveolitis, pancreatitis and
pericarditis require stopping the drug.

Sulfasalazine consists of sulfapyridine, one of the first sulfonamide drugs linked to 5-
aminosalicylic acid (5-ASA) via an azo bond. When ingested, about 30% of the drug is absorbed
passing through the liver unchanged to be partially excreted in the urine and partially returned to
the intestinal tract where it joins the nonabsorbed portion to traverse the intestine until it reaches
the colon. There the azo bond is broken by bacterial azo reductases, with release of the sulfa
moiety, which is absorbed and metabolized by the liver and excreted, never reaching the distal
colon. The 5-ASA moiety, however, is only minimally absorbed, staying within the colon to be
excreted in the feces. 5-ASA is the active moiety of sulfasalazine. Topical administration of 5-
ASA is effective in ulcerative proctitis and distal ulcerative colitis. There are now available both
topical 5-ASA enemas, known generically as mesalamine and marketed as Rowasa enemas. In
addition, there are Rowasa suppositories available for patients with ulcerative proctitis and distal
colitis. For proctitis, a suppository can be used twice a day, with a response expected within
several days and a complete remission anticipated in four to six weeks. The suppository can then
be tapered to a nighttime use only, and possibly as little as an every-other-night or every-third-
night usage will keep the patient in remission. A similar protocol is used for patients with distal
ulcerative colitis, but Rowasa enemas are used initially nightly and then after a full response is
attained in several weeks are tapered to every-other or every-third-night usage.

The topical forms of 5-ASA will be helpful for patients with distal colonic disease, but will not in
themselves be of use for disease extending beyond 50 to 60 cm in the colon and be of no help for
patients with right-sided colitis or small bowel disease. There are now several oral preparations of
5-ASA available. These include delayed release forms of mesalamine including Asacol, which is
coated with an acrylic resin, and Pentasa, which puts the 5-ASA in ethylcellulose microspheres.
These are then gradually released in the small bowel and colon.
Another form of oral 5-ASA, olsalazine, links the 5-ASA to itself via an azo bond which, as with
sulfasalazine, requires bacterial action for the release of the free 5-ASA and so is targeted
primarily for the colon. A third form, balsalazide, which links 5-ASA to an inert polymer, is now
under clinical investigation, but unlike the above three agents is now commercially available in the
United States. The oral agents have been shown to be effective in active ulcerative colitis and in
maintaining remission in ulcerative colitis, but are no more effective than sulfasalazine. Since they
are considerably more expensive than sulfasalazine, sulfasalazine usually is considered the first
choice of oral therapy for such patients. However, for patients who are intolerant or allergic to
sulfasalazine, the oral 5-ASA agents become the therapy of choice in active and remitted
ulcerative colitis.

With regard to Crohn's disease, these agents have been much less well studied. However, it does
appear that the slow-release oral 5-ASA agents are effective in Crohn's disease limited to the
small bowel as well as the colon, a finding which distinguishes them from sulfasalazine, which has
been useful in colonic disease only. Moreover, unlike the findings with sulfasalazine, the slow-
release oral 5-ASA agents appear to maintain remission in Crohn's disease, particularly for
patients with ileitis.

Most of the side effects of sulfasalazine can be attributed to the sulfapyridine moiety. Indeed, 80
to 90% of patients allergic to sulfasalazine will tolerate an oral or topical 5-ASA preparation.
However, in 10 to 20% of such patients, the allergic reaction is due to the 5-ASA moiety, and,
therefore, caution must be exercised in switching a patient who has had a severe reaction to
sulfasalazine to one of the new 5-ASA agents. Moreover, as the 5-ASA agents are being used
with greater frequency, a variety of side effects have been reported including anal irritation with
topical diarrhea particularly with the olsalazine form, alveolitis, pericarditis and pancreatitis. In
addition, there are a few scattered reports of nephrotoxicity with high-dose oral 5-ASA agents,
making it important to monitor the BUN, creatinine and urine analysis in such patients.

Corticosteroids

Topical corticosteroids in the form of enemas and foams have shown to be useful in ulcerative
proctitis and distal ulcerative colitis and with the topical 5-ASA agents can be considered for the
first-line therapy. The choice between the 5-ASA and steroid topical therapies is often difficult
and usually involves patient preference to not have steroids or the decision to keep patients on
long-term maintenance therapy, which mitigates in favor of the

5-ASA product. Currently, the Cortenema is about two thirds as expensive as the Rowasa enema.
For patients with more extensive disease who are somewhat sicker, oral prednisone usually in
doses of 40 to 60 mg per day has been effective in active disease in both active ulcerative colitis
and Crohn's disease regardless of disease distribution. However, as with topical therapy, the
standard oral steroids have not been shown to be effective at maintaining remission, and,
therefore, every attempt should be made to wean the patient off the steroid once an effect is
achieved for active disease, usually within the first two weeks of therapy. For more seriously ill
patients who require hospitalization, parenteral steroids in the form of hydrocortisone,
prednisolone or methylprednisolone are indicated. There is some evidence that intravenous ACTH
may be more effective in patients who have not recently been on steroid therapy.

Budesonide is an enema that appears to be as effective as standard topical hydrocortisone and 5-
ASA preparations. It has the advantage over standard steroids of not affecting the hypothalamic
pituitary access, since only about 10% of it is available to the systemic circulation due to rapid
metabolism on first pass through the liver. Recently, studies with a slow-release oral budesonide
preparation have shown that it is more efficacious than placebo in active Crohn's ileitis and
ileocolitis and about as effective as oral prednisolone, but with only about half the chance of
developing a side effect. It remains unclear whether oral budesonide will be effective at
maintaining remission in Crohn's disease and, if used long term, whether side effects similar to
those with standard steroids will begin to appear. These drugs remain under investigation.

Antibiotics

Metronidazole has been shown to be effective in active Crohn's disease involving the colon in
doses as low as 10 mg per kg per day. The long-term efficacy of metronidazole in maintaining
remission in Crohn's disease has not been studied. In open trials with higher doses of
metronidazole at a level of 20 mg/kg/day, the drug has been effective in perineal disease, although
withdrawal of therapy usually leads to recurrent symptoms. Metronidazole has not been shown to
be effective in active ulcerative colitis, although one study suggests that it was as effective as
sulfasalazine in maintaining remission in ulcerative colitis.

Recently, there has been increasing attention focused on the use of a variety of antibiotics other
than metronidazole in active Crohn's disease including patients with ileal disease. Ciprofloxacin
has been described in a couple of open trials and has been successful in improving the status of
patients with active disease. A small placebo-controlled trial suggested efficacy for clarithromycin
at inducing and prolonging remission. An earlier study showed similar efficacy in an open trial for
ampicillin, cephalexin, tetracycline and other broad-spectrum antibiotics. Controlled trials of these
agents are still awaited, although their use should be considered, particularly in patients who do
not respond to 5-ASA agents.

Immunomodulator Therapy

A number of drugs which modulate the immune system have been looked at in inflammatory
bowel disease. The agents in most widespread use are azathioprine and 6-mercaptopurine (6-MP).
The two can be used interchangeably, since azathioprine is metabolized to 6-MP in the liver. Both
agents have been shown to be useful in active Crohn's disease regardless of disease distribution
and in maintaining remission in Crohn's disease. More recent studies have shown similar efficacy
of these drugs in active ulcerative colitis and in maintaining remission in ulcerative colitis. There is
currently a study to look at the effectiveness of 6-MP on preventing postoperative recurrence in
Crohn's disease. Side effects with these agents have been surprisingly minimal, with pancreatitis
and leukopenia being the major short-term side effects. There have been a few cases of
lymphomas described with their use, but it is not clear whether the incidence on these agents is
any higher than in patients not on such drugs, since lymphoma may be increased in Crohn's
disease irrespective of therapy. Nonetheless, caution needs to be exercised in the use of these
agents, and the white blood count should be monitored frequently.

There is a suggestion that cyclosporin may be helpful in oral form in active Crohn's disease;
however, the relapse rate upon withdrawal is great, and since low-dose cyclosporin is not
effective at maintaining remission in Crohn's disease, its utility in this disorder is somewhat in
doubt. Intravenous cyclosporin may be useful in healing refractory fistulas in Crohn's disease, but,
again, the relapse rate upon withdrawal is high. Oral forms of cyclosporin had only limited utility
in active ulcerative colitis of a mild to moderate form. The major role for cyclosporin appears to
be in patients with severe active ulcerative colitis which is not responding to standard high-dose
parenteral corticosteroids. In two recent trials, IV cyclosporin given as a continuous infusion at
either 2 mg/kg/day or 4 mg/kg/day was effective in bringing the majority of patients into a
remission. The long-term effectiveness of oral cyclosporin in such patients and the ultimate
avoidance of colectomy is still under study. Finally, methotrexate has appeared useful in open
trials in both active Crohn's disease and active ulcerative colitis. It does not appear to be of use in
maintaining remission in ulcerative colitis and is only of marginal benefit in maintaining remission
in Crohn's disease. A recent placebo-controlled trial suggests that methotrexate is useful in active
Crohn's disease, particularly in patients who had been dependent on doses of prednisone over 20
mg/day. Long-term controlled trials of this drug are awaited.

Miscellaneous Agents

Nicotine patch has been shown to be useful in one controlled trial in active left-sided ulcerative
colitis. This is based on the previously noted epidemiologic information - that smoking seems to
protect an ulcerative colitis. Short-chain fatty-acid enemas, particularly butyrate, which provide a
fuel for epithelial cells, have been studied in open trials and appear to be effective in distal active
ulcerative colitis. A whole other array of topical agents including Bismuth, nicotine and lidocaine
have been shown to be effective in open trials, whereas a number of oral agents or parenteral
agents including allopurinol, anti-TNF antibodies, interleukin 10 and interleukin II, heparin and
tacrolimus all have appeared promising, but await further controlled trials before their use can be
advocated in IBD.

Nutritional Therapy

In ulcerative colitis, enteral and parenteral nutrition serves only as an adjunct to drug therapy for
ulcerative colitis. However, with regard to Crohn's disease, they can be used as primary therapy to
induce remission in about 65 to 70% of patients. Unfortunately, the recurrence rate upon
reinstitution of regular food is quite higher than that for standard drug therapy. However, enteral
and/or parenteral therapy may be lifesaving for patients with short bowel syndrome and is
important in promoting growth failure in children.

Surgery

Medical therapy is sufficient for about 80% of patients with ulcerative colitis, but the remainder
will ultimately need a colectomy for either intractable symptoms, the development of a
complication such as massive bleeding or toxic megacolon or the development of dysplasia or of
colon cancer. The standard surgical therapy for ulcerative colitis has been total colectomy with a
permanent ileostomy. Now the ileoanal anastomosis with pouch has emerged as the procedure of
choice for most patients, since it spares the anal opening and allows for normal continence.
Patients usually have five to six bowels movements a day, but the majority are fully continent and
their stool frequency can be controlled with Metamucil and antimotility agents. Pouchitis occurs
in 20 to 50% of patients, but can usually be treated with metronidazole, ciprofloxacin or other
antibiotics. This procedure cannot be offered to patients with Crohn's disease because of the high
recurrence rate of the disease in the small bowel ileal pouch. An innovative surgical therapy for
Crohn's disease is strictureplasty for those patients with multiple small bowel strictures. This
avoids unnecessary resection. Also, the concept in Crohn's disease is for minimal resection,
removing only grossly involved areas of bowel and not being concerned with the removal of all
microscopic disease. For Crohn's surgery, the most common procedure is a resection with an
anastomosis. Unfortunately, the recurrence rate after such surgery is high, occurring with a
frequency of about 10% per year. However, studies have emphasized that resection in Crohn's
disease does improve the quality of life, and the majority of patients have much less psychosocial
dysfunction, even years after surgery and even after clinical recurrence.

References

Podolsky DK. Inflammatory Bowel Disease. N Engl J Med 1991; 325:928-37,1008-16.

Peppercorn MA. Inflammatory Bowel Disease. Gastroentero1ogy Clinics of North America 1995;
Vol 24, No 3.

Hanauer SB. Inflammatory Bowel Disease - Medical Therapy. N Engl J Med 1996;335:841-8.

Mowschenson PM. New surgical approaches in IBD. In Peppercorn MA (ed), Seminars in Colon
and Rectal Surgery, 1993. pp 25-36.

				
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