Inflammatory Bowel Disease Treatment & Management

The care of a patient with inflammatory bowel disease (IBD) can be either medical or surgical in nature or, commonly, a combination of both. The medical approach for patients with IBD is symptomatic (flaring) care and generally follows a step-wise approach to medication therapy, with progression of the medical regimen until a response is achieved. Whether patients whose disease is in remission benefit from continuing to take aminosalicylate is controversial. In persons with Crohn disease, earlier data suggested that postoperative recurrences are decreased in frequency and severity, although later data suggest that this preventive effect may not apply to flares of this disease.

Because patients report symptoms (eg, diarrhea, spasm/pain, epigastric discomfort) and not inflammation per se, symptomatic relief is appropriate when indicated. This includes therapy with antidiarrheal agents, bile acid-binding agents, antispasmodics, and acid suppressants, as needed.

Loperamide and the combination of diphenoxylate and atropine are useful in mild disease to reduce the number of bowel movements and to relieve rectal urgency. Cholestyramine, a resin that binds bile salts, is useful for reducing diarrhea in patients with Crohn disease who have had ileal resections. The anticholinergic agent dicyclomine may help relieve intestinal spasms.

These medications are not without complications, and caution is necessary. Antidiarrheal and anticholinergic medications must be avoided in acute severe disease, because they may precipitate toxic megacolon. Avoid the long-term use of narcotics for pain. An iron supplement should be added when significant rectal bleeding is present.

A step-wise approach, such as the following, may be taken. With this approach, the most benign (or temporary) drugs are used first. As they fail to provide relief, drugs from a higher step are used.

The first step in medication therapy for IBD is usually aminosalicylates; no advantage has been demonstrated for any particular agent for either ulcerative colitis or Crohn disease. For Crohn disease, metronidazole or ciprofloxacin is occasionally used, particularly for perianal disease or an inflammatory mass.

If the patient's condition fails to respond to aminosalicylates, the second step is corticosteroids, which tend to provide rapid relief of symptoms and a significant decrease in inflammation. The most common range for moderate flares of IBD is oral (PO) prednisone at 10-40 mg/d; for more severe flares, the higher end of the range is used (occasionally even higher doses are used). Once a clinical response is seen, the dose is tapered. Most patients who use PO corticosteroids can only occasionally tolerate a relatively rapid taper after a response is achieved; occasionally, a very prolonged steroid taper is necessary to prevent relapse. When the latter situation occurs, consider the use of alternative drugs (immune modifiers or anti-tumor necrosis factor [TNF] therapy).

The immune-modifying agents are step III drugs and are used if corticosteroids fail or are required for prolonged periods. Infliximab is also a step III drug that can be used in some situations in patients with Crohn disease and ulcerative colitis.

The experimental agents are step IV drugs and are used only after the previous steps fail and, then, are administered only by physicians familiar with their use.

Note that drugs from all steps may be used additively; in general, the goal is to wean the patient off steroids as soon as possible to prevent long-term adverse effects from these agents. Ardizzone et al suggest that a lack of mucosal healing after corticosteroid therapy is the only factor associated with negative outcomes at 5 years.^[11] Opinions differ regarding the use of certain agents in this step-wise approach.

The 5 oral aminosalicylate preparations available for use in the United States are sulfasalazine (Azulfidine), mesalamine (Asacol, Pentasa), balsalazide (Colazal), and olsalazine (Dipentum). Enema and suppository formulations are also available. All of these are derivatives of 5-aminosalicylic acid (5-ASA); the major differences are in the mechanism of delivery. Some of these also have unique adverse effects that other agents of this class lack. All of the aminosalicylates are useful for treating flares of IBD and for maintaining remission. None of the aminosalicylates has been proven to have greater efficacy for the treatment of ulcerative colitis or Crohn disease over any of the others. All of them are clearly more effective in persons with ulcerative colitis than in persons with Crohn disease; in persons with Crohn disease, the primarily utility is for colonic disease. Aminosalicylates may prevent recurrence after surgery in patients with Crohn disease.^[12]

Supplementation of the high-potency probiotic mixtures ( such as VSL#3) have been shown in some reports to reduce ulcerative colitis disease activity index scores in patients with mild-to-moderate relapsing ulcerative colitis who are being treated with 5-ASA. Studies in Crohn disease are much less promising. VSL#3 has also been shown to reduce rectal bleeding in those patients.^{[13, 14, 15]}

The antibiotics metronidazole and ciprofloxacin are the most commonly used antibiotics in persons with IBD. According to a systemic review, antituberculosis therapy, macrolides, fluoroquinolones, 5-nitroimidazoles, and rifaximin (alone or in combination) have been shown to induce remission in active Crohn disease and ulcerative colitis.^[16] Antibiotics are used only sparingly in persons with ulcerative colitis, because ulcerative colitis increases the risk of developing antibiotic-associated pseudomembranous colitis. When used in persons with ulcerative colitis, antibiotics are most commonly administered in the perioperative setting. However, in persons with Crohn disease, antibiotics are used for various indications, most commonly for perianal disease. They are also used for fistulae and inflammatory masses in the abdomen, and they may have some efficacy in treating ileitis. The antibiotics have potential adverse effects, including nausea, anorexia, diarrhea,andmonilial(candidal)infections;peripheralneuropathy can be observed in association with metronidazole use and, when present, requires discontinuation of therapy with that drug.

Corticosteroids are rapid-acting anti-inflammatory agents used in the treatment of IBD. Indications are for acute flares of disease only; corticosteroids have no role in the maintenance of remission. Corticosteroids may be administered by various routes depending on the location and severity of disease; they may be administered intravenously (ie, methylprednisolone, hydrocortisone), orally (ie, prednisone, prednisolone, budesonide, dexamethasone), or topically (ie, enema, suppository, or foam preparations).

Corticosteroids are limited by their adverse effects, particularly with prolonged use. The potential complications of corticosteroid use are multiple and include fluid and electrolyte abnormalities, osteoporosis, aseptic necrosis, peptic ulcers, cataracts, neurologic and endocrine dysfunctions, infectious complications, and occasional psychiatric disorders (including psychosis).

The consensus regarding treatment with these agents is that they should be tapered as rapidly as possible. Corticosteroids do not have a role in maintaining remission, and their use may lead to debilitating illness, particularly after long-term use.

Warn patients who refuse to try more aggressive therapies and who insist on continuing to take corticosteroids of the potential for long-term harm with these drugs, and take care to document these warnings and the alternatives offered in the medical record. Recommend to any patient who requires more than the rare short course of steroids that a yearly ophthalmologic examination is warranted because of the risk of cataract development.

According to 2006 guidelines from the American Gastroenterological Association (AGA), periodic assessment of bone mineral density is recommended for patients taking steroids for more than 3 months.^[17] Some data assert that some agents used for osteoporosis prevention and treatment (eg, the bisphosphonates) are useful for preventing the bone loss associated with corticosteroid use.

Intravenous corticosteroids

IV corticosteroids are often used for patients who are severely ill and hospitalized; few data have been published on the optimum dosage of IV (or PO form) corticosteroids. The generally used upper ends of dosing are IV methylprednisolone at 40 mg every 6 hours or IV hydrocortisone at 100 mg every 8 hours. Some situations mandate a higher initial IV, but many practitioners start hospitalized patients at lower IV doses.

In general, once a clinical response is observed (typically within a 1-2 d, occasionally longer), the dose of the IV corticosteroid can be tapered. Before hospital discharge, conversion to a PO corticosteroid is made; further dosage tapering can be accomplished in an outpatient setting.

Oral corticosteroids

When PO corticosteroids are used, dosing is highly variable and few data have been published to guide optimal dosing. The most common range for moderate flares of IBD is prednisone at 10-40 mg/d; for more severe flares, the higher end of the range is used (occasionally even higher doses are used). Again, once a clinical response is seen, the dose is tapered. Most patients who use PO corticosteroids can only occasionally tolerate a relatively rapid taper after a response is achieved; occasionally, a very prolonged steroid taper is necessary to prevent relapse. When the latter situation occurs, consider the use of alternative drugs (immune modifiers or anti-TNF therapy).

Budesonide (Entocort EC), a synthetic corticosteroid, is available for Crohn disease with ileal or ileocecal involvement.^[10] Budesonide is poorly absorbed and has extensive first-pass metabolism, which limits systemic adverse effects.^[17] However, some absorption occurs and may slow growth in adolescents. Budesonide is less effective than other standard glucocorticosteroids and is of no benefit in preventing relapse.^[16]

According to AGA guidelines, ileal-release preparations of budesonide are indicated for the treatment of patients with mild to moderate ileal and right-sided colonic Crohn disease. These preparations are not effective in patients with ulcerative colitis.^[17]

Topical corticosteroids

Topical corticosteroids are used in persons with distal colonic disease in a manner similar to topical mesalamine; the major difference is that even though topical mesalamine may be used to help maintain remission, topical corticosteroids are used for active disease and have only a small role in the maintenance of remission. AGA guidelines advise that topical therapy with either hydrocortisone (grade A recommendation) or budesonide (grade B recommendation) is effective for distal colonic inflammation in patients with mild to moderate IBD.^[17]

Rectal corticosteroids

Cortenema, Cortifoam, and Anusol-HC suppositories are useful in treating distal disease (proctitis and proctosigmoiditis).

The immune modifiers 6-MP and azathioprine are used in patients with IBD in whom remission is difficult to maintain with the aminosalicylates alone. Immune modifiers work by causing a reduction in the lymphocyte count, and because of that mechanism of action, their onset of action is relatively slow (typically 2-3 mo). These agents are used most commonly for their steroid-sparing action in persons with refractory disease; they are also used as primary treatment for fistulae and the maintenance of remission in patients intolerant of aminosalicylates.

The AGA, in accordance with the US Food and Drug Administration, recommends that patients undergo assessment of thiopurine methyltransferase (TPMT) genotype or phenotype before starting therapy with azathioprine or 6-MP. Individuals who have low enzyme activity or are homozygous deficient in TPMT mutation are at extreme risk of very severe leukopenia, with potential septic complications, and may not be good candidates for therapy with these drugs.^[17]

Individuals with heterozygous TPMT activity respond to therapy but are prone to myelotoxicity, although this can be minimized with use of lower doses. These patients, as well as those with wild-type TPMT activity, require monitoring for complications.^[17]

Use of immune modifiers mandates monitoring of blood parameters; they can cause significant neutropenia or pancytopenia that would warrant a dose reduction or discontinuation. Routine CBC counts with differentials and platelet counts are checked monthly, and LFTs can be performed intermittently. After a year of stable dosing with no difficulties with blood counts (except the expected lymphopenia), the intervals between blood count monitoring can be increased.

The cytopenic effect is typically dose dependent, although some patients are more sensitive than others. Typical dosing of the immune modifiers (either 6-MP or azathioprine) is 1-2 mg/kg/d. If needed, the dose can be increased to the point when cytopenia occurs; obviously, at higher doses, closer monitoring is warranted. Blood tests are available to measure metabolite levels, but the results have not been shown in independent studies to have any correlation with clinical efficacy. These blood tests for monitoring toxicity offer little advantage (but much greater expense) over monitoring CBC counts and LFT results.

Other adverse effects of the immune modifiers include fever, rash, infectious complications, hepatitis, pancreatitis, and bone marrow depression. The most common reason for discontinuing the immune modifiers within the first few weeks is the development of abdominal pain; occasionally, a biochemically demonstrable pancreatitis occurs.

Concerns have been raised about the development of malignancy in patients taking 6-MP and azathioprine. Because the population that requires these medications is already at higher risk for the development of malignancy, the available data on the use of 6-MP or azathioprine may be insufficient and may not demonstrate a significant increase in the risk of malignancy.

Additional step III agents work by a different mechanism. Infliximab (Remicade) is an anti-TNF-alpha monoclonal antibody administered by infusion for the treatment of Crohn disease. Infliximab is FDA approved for both ulcerative colitis and Crohn disease, although it does appear to have a higher efficacy rate in Crohn disease. Infliximab is generally administered as 3 separate infusions of 5 mg/kg for the treatment of moderate to severe IBD at weeks 0, 2, and 6, often followed by doses every 8 weeks for maintenance of remission.

A systemic review of the efficacy of biological therapies in IBD confirmed that anti-TNF-alpha antibodies and natalizumab were effective in inducing remission of active Crohn disease.^[18]

For Crohn disease, the response rate is 80% and the induction of remission rate is 50% after a single dose; with multiple dosing, higher rates of remission are attained. For ulcerative colitis, the response rates are 50-70%.

Infliximab is also indicated for the treatment of fistulizing Crohn disease; for this indication, the fistula responds (closes) in 68% of patients treated with infliximab, although 12% develop an abscess. The response can be maintained by continuing regular dosing (ie, every 8 wk) after the induction dose.

According to AGA guidelines, infliximab is indicated for the treatment of patients with Crohn disease or ulcerative colitis who do not achieve adequate clinical response despite treatment with conventional therapy (ie, a corticosteroid or an immunosuppressive agent) and for treatment of fistulizing Crohn disease that is refractory to conventional therapy (ie, antibiotics, surgical drainage with examination under anesthesia, and/or immunosuppressive therapy). Patients who respond to induction therapy with infliximab should receive maintenance therapy.^[17]

The adverse effects of infliximab commonly include hypersensitivity and flulike symptoms; the latter can often be avoided by pretreatment with acetaminophen and diphenhydramine. Rare reports of lupuslike reactions and lymphoproliferative malignancies have been reported, although whether the malignancies are related to the drug or to the underlying disease process remains uncertain.

The practitioner is advised to have the patient seek insurance approval for the administration of this medication, because infliximab is extremely expensive (typically, several thousand dollars per dose). Infliximab has an excellent response rate for Crohn disease (>80%); however, its response rate for ulcerative colitis is clearly less (approximately 50%).

Other newer anti-TNF agents include adalimumab (Humira), which is given by SC injection every 2 weeks after a loading dose of 6 injections, and certolizumab pegol (Cimzia), which is given by SC injection every 4 weeks.

Natalizumab (Tysabri; formerly called Antegrin), an agent aimed at preventing the accumulation of lymphocytes in the diseased bowel by blocking the effects of integrin, has been approved by the FDA, but it is only available through a restricted distribution program. Natalizumab is an IV medication that has shown efficacy in Crohn disease, but it is not as effective as anti-TNF agents. Natalizumab has been linked to reports of progressive multifocal leukoencephalopathy (PML) (a potentially fatal opportunistic viral infection) in 3 patients.

Generally, use these agents as part of an experimental protocol or in a setting in which the toxicities of the agents can be rapidly recognized and managed. Examples of some agents are provided, but a review of the literature is warranted before using them. In most cases, some subsets of patients have a clinical response; in general, large placebo-controlled trials have not yet established efficacy for these agents for the treatment of IBD.

Various experimental agents tend to be more disease-specific (ie, an agent works for Crohn disease but not ulcerative colitis, or vice versa). Experimental agents used in persons with Crohn disease include methotrexate (12.5-25 mg/wk PO or IM), thalidomide (50-300 mg/d PO), and IL-11 (1 mg/wk SC). Experimental agents used in persons with ulcerative colitis include cyclosporine A at an IV dose of 2-4 mg/kg/d (measure level; convert to PO dosing at 2-3 times the IV dose), nicotine patch (14-21 mg/d via topical patch), butyrate enema (100 mL per rectum twice daily), and heparin (10,000 U SC twice daily). Multiple contraindications, interactions, and precautions are associated with these drugs.

AGA guidelines advise that IV cyclosporine is effective for avoiding surgery in patients with ulcerative colitis who have failed to respond to 7-10 days of high-dose oral or parenteral corticosteroids. Concomitant administration of IV corticosteroids is recommended in these cases. Patients who respond typically require continuation of therapy with oral cyclosporine for a few months, along with a tapering dose of corticosteroids, initiation of azathioprine or 6-MP therapy, and prophylaxis against Pneumocystis jiroveci.^[17]

Admit patients to the hospital if surgical intervention is anticipated or if their condition does not respond to outpatient treatment, they are dehydrated, or they have uncontrolled pain or diarrhea. Start IV hydration. If indicated, obtain an abdominal flat plate image to exclude obstruction or megacolon. If the patient is nauseated or vomiting or has evidence of obstruction or megacolon, nasogastric (NG) intubation is indicated. Consider consultation with a surgeon.

If the patient has ulcerative colitis, send a stool sample for C difficile toxin titer testing; also send one for routine culture and sensitivity testing if the patient has a new diagnosis of IBD. Laboratory studies to be considered include a CBC count with differential, albumin level, ESR level, glucose value, calcium level, magnesium level, phosphate value, electrolyte status, blood urea nitrogen (BUN)/creatinine values, and a pregnancy test in females of childbearing age.

Initiate treatment with a PO aminosalicylate, IV corticosteroids, and metronidazole or ciprofloxacin (if antibiotics are indicated). Electrolyte correction and, potentially, transfusion, can be performed if indicated based on laboratory findings.

Keep patients on a diet of nothing by mouth (NPO), except for medications (Crohn disease only); patients with ulcerative colitis may maintain a regular diet unless megacolon is present or surgery is being contemplated. Consider additional consultations with a registered dietitian and a stoma nurse if indicated. Consider line placement of central venous access. Monitor severe cases for fat malabsorption. Administer folate supplementation as needed.

If the abdominal flat plate findings were not diagnostic or if diagnostic concerns remain, order a barium study (small bowel series or barium enema). Although a colonoscopic evaluation may also be contemplated, consider the increased risk of perforation in persons with acute colitis. Assess and correct the posthydration CBC count and electrolyte values, as indicated. Depending on the response to the initial interventions, advancement of the diet may be considered.

By the second hospital day, most patients should be showing clear evidence of clinical improvement. Assess the electrolyte status if IV fluids are still being administered. Consider advancement of the diet. The corticosteroid dose can be tapered. If the patient is not improving, consider other treatment options; these may include hyperalimentation, other medical therapies, surgical intervention, or transfer to a tertiary care facility. Consider skipping to interventions typically enacted on day 3 or 4 (or discharge).

Hospital day 3 is similar to day 2. The corticosteroid dose can be reduced, and a switch to oral forms of all medications can be contemplated. If home treatments are needed (eg, home hyperalimentation), initiate arrangements for these. The diet can be advanced as tolerated. Consider skipping to day 4 or 5 interventions.

Continue to advance the diet, as tolerated. Continue the switch to oral medications. Many patients with a flare of Crohn disease or ulcerative colitis may be discharged by this time (occasionally even sooner); some may require another day of IV therapy.

If no progress has been made in the patient's condition since admission, additional treatments are necessary, including surgery (see Surgical Intervention for Inflammatory Bowel Disease, below) or more aggressive medical treatments. Again, consider transfer to a tertiary care facility. If the patient has been unable to tolerate an oral diet, initiate hyperalimentation and/or reconsider surgical intervention.

Most patients should be able to be discharged on or before the fifth hospital day. A regular diet should be tolerated, with some restrictions if strictures are present. An ESR level may be obtained to assist in future disease assessment but its result is unlikely to alter current management.

Discharge the patient on oral medications, with appropriate follow-up as an outpatient, typically within a few weeks.

Immune modifiers

If patients have difficulty with reduction in the dose of corticosteroids, have IBD that is refractory to corticosteroid therapy, or have frequent flares that require corticosteroid therapy, use of one of the immunomodulatory agents, either 6-MP or azathioprine, may be considered. Typical dosing of the immune modifiers (either 6-MP or azathioprine) is 1-2 mg/kg/d. If needed, the dose can be increased to the point when cytopenia occurs; obviously, at higher doses, closer monitoring is warranted.

These agents are not used for acute flares because the time from the initiation of treatment to the onset of significant action may be as long as 2-3 months. Response to immune modifiers may be dose dependent; monitoring of blood counts is required to protect the patient from the hematologic toxicity associated with these agents. Some authors suggest earlier use of immune modifiers.

Monoclonal antibodies

An alternative agent is infliximab, a monoclonal antibody against TNF-alpha. The FDA approved infliximab for the treatment of Crohn disease in July 2005, then for the treatment of ulcerative colitis in August 2005. Administer this agent by IV infusion. This medication is generally administered in 3 doses of 5 mg/kg over 6 weeks (at weeks 0, 2, and 6) followed by a maintenance regimen. Administering the drug every 8 weeks has been demonstrated to be effective for maintaining remission.

The practitioner is advised to have the patient seek insurance approval for the administration of this medication, because infliximab is extremely expensive (typically, several thousand dollars per dose). Infliximab has an excellent response rate for Crohn disease (>80%); however, its response rate for ulcerative colitis is clearly less (approximately 50%). Adalimumab is a good alternative for Crohn disease. This is administered as 160 mg SC at week 0 (four 40-mg injections), then 80 mg SC at week 2 (two 40-mg injections), then 40 mg SC q week.

Experimental therapies

Other medical treatment of refractory IBD involves agents that have less well-demonstrated levels of efficacy but have been shown to be useful in some subsets of patients. For Crohn disease, PO or intramuscular (IM) methotrexate 12.5-25 mg/wk, PO thalidomide 50-300 mg/d, and SC interleukin (IL)-11 at 1 mg/wk may fall into this category. For ulcerative colitis, cyclosporin A (usually IV of 2-4 mg/kg/d for overwhelming disease) (measure level; convert to PO dosing at 2-3 times the IV dose), topical nicotine patches 14-21 mg/d, butyrate enema 100 mL per rectum twice daily, and heparin 10,000 U SC twice daily fall into this category.

Hyperbaric oxygen therapy may be helpful in the treatment of IBD that is unresponsive to other therapies. Its therapeutic efficacy appears to result from decreased generation of prostaglandin E2. Previous work has linked mucosal prostaglandin E2 to the intestinal damage associated with IBD.^[5]

Finally, a number of clinical trials of biologic agents and diets are being conducted and may demonstrate efficacy in persons with IBD.

Smoking cessation

A lifestyle change that may benefit patients with Crohn disease is smoking cessation. Tobacco use has been linked to increases in the number and severity of flares of Crohn disease, and smoking cessation is occasionally sufficient to achieve remission in a patient with refractory Crohn disease.

Tertiary care

The decision to transfer care of a patient (inpatient or outpatient) depends on the expertise and comfort level of the treating physician. Outpatient requests for a tertiary opinion should occur when patients have disease that is difficult to control with aminosalicylates and occasional brief courses of corticosteroids.

Relatively infrequent use and the monitoring necessary for azathioprine, 6-MP, and infliximab prompt some physicians to choose to refer patients to tertiary care centers when the need for these agents becomes apparent; others are comfortable handling these agents themselves.

For patients with refractory disease or those in whom corticosteroids cannot be weaned, referral for a second opinion generally is wise. Transfer inpatients for a tertiary opinion if the patient's condition is not responding to IV steroids within a few days of admission; alternatively, strongly consider surgical intervention (see Surgical Intervention for Inflammatory Bowel Disease, below).

If a step-wise approach is observed, the least amount of medication that is effective can be used. A general rule of thumb is that once remission is achieved, the medications used to achieve remission are continued (except for steroids, which should be tapered off, as these drugs do not have a role in maintaining remission,^[8] and their use may lead to debilitating illness, particularly after long-term use). Despite the widespread availability of home infusion, IV corticosteroids are still used only in hospital settings because of potential problems and the dosing schedule.

Home infusion of IV hyperalimentation is increasingly available for rare patients with Crohn disease in whom prolonged bowel rest is necessary. The short bowel may require prolonged hyperalimentation. Home IV antibiotics can also be arranged in this setting, if necessary.

The approach to surgical treatment of IBD varies depending on the disease. Most important, ulcerative colitis is a surgically curable disease because the disease is limited to the colon. However, Crohn disease can involve any segment of the GI tract from the mouth to the anus; thus, surgical resection is not curative. On the contrary, excessive surgical intervention can leave the patient with a crippling short bowel syndrome. Situations arise in Crohn disease in which surgical intervention without resection can be used to defunctionalize the colon in order to possibly allow healing of distal disease.

Ulcerative colitis

Consider surgical intervention for patients in whom medical therapy fails, as it is curative for colonic disease and potential colonic malignancy. The indications for colectomy are the following:

• Inflammation is difficult to control
• Early changes are found during surveillance (high-grade dysplasia, low-grade dysplasia in some instances)
• Strictures are present
• There are significant adverse medication effects
• An unacceptable quality of life exists referable to the ulcerative colitis

The surgical options for ulcerative colitis vary. Currently, the 2 most common choices are proctocolectomy with ileostomy and total colectomy with ileoanal anastomosis.

Although segmental resection is rarely performed, total proctocolectomy is common. Total proctocolectomy with ileostomy creation is the simplest procedure with the lowest overall complication rate. A variation on this is the continent ileostomy or Koch pouch, which creates an ileal reservoir that can be emptied with catheterization several times per day. However, incontinence from the pouch may necessitate use of an ileostomy bag. A colectomy may be performed, leaving a few centimeters of rectum intact; this ensures anal continence, but continued malignancy surveillance is needed for any colonic mucosa that remains, and the remaining diseased rectal mucosa can continue to be problematic from a symptomatic standpoint.

Using a strictly defined cohort of patients, a study by Kiran et al did not identify segmental bowel resection as an independent risk factor for recurrence or stoma formation. The study found no reduction in quality of life (QoL) scores suggestive of an adverse effect of recurrence.^[19] Nevertheless, segmental colectomy provides good function, and the data support a conservative approach with anastomosis in anatomically-linked Crohn disease.

The most technically demanding surgical option is ileal pouch/anal anastomosis (IPAA). In this multistage procedure, a diverting ileostomy is performed and an ileal pouch is created and anastomosed directly to the anus, with complete removal of the rectal mucosa. After the ileoanal anastomosis is healed, the ileostomy is taken down and flow through the anus is reestablished. The major complications of this procedure are anal incontinence and impotence. Occasionally, postoperative pouchitis is a problem. If the diagnosis of ulcerative colitis is incorrect and this procedure is performed on a patient with colonic Crohn disease, the likelihood of disease recurrence at the ileoanal anastomosis is high, which requires takedown, ileostomy creation, and loss of additional small bowel. When performed by a surgeon skilled in this technique, IPAA offers an excellent option for younger patients with ulcerative colitis and concerns about body image.

Elective surgery can sometimes be performed laparoscopically. For fulminant colitis, the surgical procedure of choice consists of a subtotal colectomy with end ileostomy and creation of a Hartman pouch.

Postoperative complications of colectomy for ulcerative colitis have not been well characterized until recently. A population-based study by de Silva et al showed the primary predictors of severe postoperative complications to be age and multiple comorbidities. Furthermore, the worst outcomes occurred when surgery was performed 14 or more days after hospital admission under emergency conditions in patients who had no response to medical treatment.^[20]

Previous proctocolectomy or ileostomy is not an impediment to successful pregnancy.

Crohn disease

Surgery in Crohn disease is most commonly performed for complications of the disease (ie, strictures, fistulae, bleeding) rather than for the disease itself. Approximately 50% of patients with Crohn disease require surgical intervention; in general, the surgeons resect only as much bowel as necessary to correct the problem, because the recurrence rate after surgery is quite high. The rate of disease recurrence is 25-50% within 1 year for patients whose condition has responded to medical management; this rate approaches 100% for patients who require surgery. About 50% of patients undergoing surgery require a second operation; of these patients, 50% have a third operation.

Although surgery is an important treatment option for Crohn disease, patients should be aware that it is not curative and that disease recurrence after surgery is the rule. Post surgery, disease recurrence is generally in a pattern that mimics the original disease pattern, often on one or both sides of the surgical anastomosis. Endoscopic evidence of recurrent inflammation is present in 93% of patients 1 year after surgery for Crohn disease.

The most straightforward surgery for Crohn disease is the segmental resection, in which a segment of intestine with active Crohn disease or a stricture is resected and the remaining bowel is reanastomosed. This surgery requires margins of resection; in general, as little bowel as possible is resected because the risk of disease recurrence is significant.^[21]

In patients with a very short cicatrix (scar tissue) stricture, a bowel-sparing stricturoplasty can be performed. In this procedure, a longitudinal incision is made across the stricture, and then the incision is repaired with a vertical suture. All mucosa is spared, and the obstruction is relieved. As many as 6-8 stricturoplasties can be performed in a single operative session.

Stricturoplasty is associated with a 6-8% septic complication rate (2-3% of patients require reoperation); this can generally be prevented with optimal preoperative management to control the inflammatory component of the stricture before surgical intervention.

Ileorectal or ileocolonic anastomosis is an option available to some patients who have distal ileal or proximal colonic disease. This is a variation on the simple segmental resection.

In patients with severe perianal fistulae, a diverting ileostomy or colostomy is a surgical option. In this procedure, the distal colon is defunctionalized and a temporary ileostomy or colostomy is created. The defunctionalized rectum is allowed to heal, and the ileostomy or colostomy is then taken down 6 months or 1 year later. Many patients who pursue this option choose to forego reanastomosis after experiencing a stoma and a consequent improvement in quality of life. Approximately 50% of patients who have the reanastomosis performed have recurrences of perianal disease.

Symptomatic enteroenteric fistulae are generally resected, although recurrence is common. Postoperative medical therapy is often used to prevent recurrence, although data are lacking on efficacy. A meta-analysis of 9 randomized trials suggested that 5-ASA preparations may provide a modest benefit for the maintenance of surgically-induced remission in patients with Crohn disease.^[12]

In addition to possible studies performed by an endoscopist or radiologist, patients with IBD who are admitted to a medical facility typically require consultation with a surgeon.

Early consultation with a surgeon is particularly useful in patients with stricturing or fistulizing disease and in patients with ulcerative colitis who experience frequent flares, have significant adverse effects from medications, or have an unacceptable quality of life. Consult a surgeon for complicating obstruction, hemorrhage, perforation, abscess or fistula formation, toxic megacolon, or perianal disease.

An interventional radiologist may be consulted when percutaneous drainage of an abscess is desired.

Extracolonic manifestations (ie, uveitis, arthritis, dermatitis, sclerosing cholangitis) are best managed with the aid of specialty consultation.

Consider arranging consultations for patients with a registered dietitian and a stoma nurse, if indicated.

No known dietary or lifestyle changes prevent IBD, and no known dietary substances cause activation of IBD. However, tobacco use has been linked to increases in the number and severity of flares of Crohn disease, and smoking cessation is occasionally sufficient to achieve remission in a patient with refractory Crohn disease.

Lactose intolerance is common in persons with Crohn disease or ulcerative colitis and some patients with other types of IBD.

Although diet has been well demonstrated to have little or no influence on inflammatory activity in persons with ulcerative colitis, it may influence symptoms. For this reason, patients are often advised to make a variety of diet modifications, especially the adaptation of a low-residue diet, although the evidence does not support a low-residue diet as beneficial in the treatment of ulcerative colitis. However, such a diet might decrease the frequency of bowel movements.

Unlike in persons with ulcerative colitis, diet can influence inflammatory activity in persons with Crohn disease. Status NPO can hasten the reduction of inflammation, as might the use of a liquid or predigested formula for enteral feeding. Although a meta-analysis in 1995 demonstrated that steroids were superior to liquid diet alone for Crohn disease, a liquid diet seemed superior to a regular diet for reducing inflammation. The problem with using enteral liquid diets, especially the predigested formulations, is that palatability limits the intake of adequate energy (calories) to meet patient requirements. Parenteral alimentation may be needed.

In a prospective study, Yamamoto et al found concomitant enteral nutrition during infliximab maintenance therapy did not significantly increase the maintenance rate of clinical remission in patients with Crohn disease.^[22] Fifty-six patients with quiescent Crohn disease on maintenance infliximab therapy (5 mg/kg, q 8 wk) were evaluated; over 56 weeks of follow-up, 32 patients received concomitant enteral nutrition (elemental diet infusion at night; a low-fat diet at day), whereas the remaining 24 patients did not receive enteral nutrition and had no diet restrictions. The investigators determined there was no significant difference between the 2 groups with respect to the Crohn disease activity index (CDAI) (CDAI < 150 = clinical remission).^[22]

Generally, patients do not need to limit activity when IBD is quiescent. Even during flares of disease activity, activity is limited only by the extent of fatigue and the abdominal pain or diarrhea the patient is experiencing. When abdominal pain persists beyond medical therapy-induced resolution of the active inflammation, other causes of pain must be considered, including nephrolithiasis, abscess, stricture, IBS, and psychiatric disease.

In most instances, diarrhea limits activity primarily because of the lack of immediate access to toilet facilities in many locations and/or occupations. This can often be resolved with employers. Occasionally, dehydration may be an issue, requiring IV hydration or the use of oral rehydration solutions.

Moderate-to-vigorous physical activity for as long as 12 weeks has been shown to improve symptom scores and many specific quality-of-life dimensions, including energy, sleep, emotion, and physical functioning.^[23] This degree of activity was defined as 20-60 minutes of intense exercise 3-5 days per week. The improvements occur despite lack of change in body weight, oral-anal transit time, bowel movements per week, or stool consistency. This study also highlights that symptomatic deterioration is more likely in physically inactive individuals.

Most outpatients' disease is in remission and requires little or no medication other than aminosalicylates (perhaps). Flares of IBD can generally be managed in an outpatient setting, primarily by stepping up the medication as described in the step-wise approach (see Medication).

The biggest concern for outpatients is the duration and dosing of oral corticosteroids. An adequate dose to suppress inflammation (and thus symptoms) may typically be in the range of 20-40 mg of prednisone per day. Once symptoms are controlled, a rapid taper of the steroid follows. Patients in whom flares are frequent (>1-2 times/y), in whom the duration of steroid use is long (more than a few wk/y), in whom reduction of the steroid dose causes recurrence of symptoms, or in whom steroids do not appear to be working are candidates for more intensive therapy. This higher step would include immune-modifying agents, infliximab, or experimental agents.

A health maintenance issue of particular importance to patients with IBD is a reduction in bone density, either from decreased calcium absorption (because of the underlying disease process) or because of corticosteroid use. Crippling osteoporosis can be a very serious complication for patients with IBD. The threshold for obtaining bone density studies should be low, and treatment (with bisphosphonates and calcium supplements) can be initiated in patients with significantly low bone density.

All of the aminosalicylates and the corticosteroids appear to be safe in women in all phases of fertility, pregnancy, and lactation. Men should avoid sulfasalazine (Azulfidine) during periods when they and their mates are attempting to become pregnant.

Reproduction

In women, fertility is normal or only minimally impaired. Women considering pregnancy should not start immune modifiers (ie, 6-MP, azathioprine). The majority of case reports and small series show no adverse outcomes of pregnancies in patients with IBD who are taking immune modifiers. Birth defects are also reported, but not at a rate higher than in the general population. If a patient is taking an immune modifier and becomes pregnant, current data support the consensus that continuing the immune modifier throughout the pregnancy is the safest course of action for both the mother and the fetus.^[24] Vigilance for birth defects is appropriate.

For men with IBD, the major concern is the medications needed for treatment. Sulfasalazine can decrease sperm counts and sperm motility, causing a functional azoospermia; the other aminosalicylates do not seem to have this effect. The sperm effects are reversible by discontinuing the sulfasalazine. No firm evidence indicates that the use of immune modifiers in the father leads to more birth defects, although this has been suggested.

Pregnancy

Most infants are born to parents with IBD are healthy. The prevalence of prematurity, stillbirth, and birth defects is similar to that of the general population. The prevalence of spontaneous abortion is slightly higher in patients with IBD (12.2%) than in the general population (9.9%). Previous proctocolectomy or ileostomy is not an impediment to successful pregnancy.

In general, the aminosalicylates, including sulfasalazine, are safe during pregnancy. Folate supplements should be taken. Corticosteroids are also safe, but if high doses are needed near the end of the pregnancy, monitor the infant for signs of adrenal suppression. The literature suggests that continuation of immune modifiers (ie, 6-MP, azathioprine) may be safe in pregnancy. Metronidazole (Flagyl) and ciprofloxacin (Cipro) are safe in pregnancy. The topical agents are generally safe in pregnancy.

Breastfeeding

Mothers who require medication to control of their IBD should strongly consider bottle feeding their infants. Sulfasalazine metabolites can be detected in breast milk; exercise caution. Low concentrations of mesalamine and higher concentrations of its metabolites can be detected in breast milk. The significance of this is unknown. Corticosteroids can also be detected in breast milk.

Immune modifiers are excreted in breast milk and should be considered only on a case-by-case basis; either the immune modifier should be discontinued or the infant should be bottle fed.

Antibiotics (ie, metronidazole [Flagyl], ciprofloxacin [Cipro]) should generally be avoided during lactation as they are excreted in breast milk; discontinue breastfeeding or discontinue the drugs. These agents are probably safe for fertility and during pregnancy.

Although small amounts of the topical agents are absorbed, and thus may be excreted in breast milk, the concentrations are much lower than with the oral forms of the same medications. These medications are probably reasonably safe in breastfeeding.