Treatment: Inflammatory Bowel Diseases

SUPPORTIVE: Antidiarrheal agents (diphenoxylate and atropine, loperamide) in mild disease; IV hydration and blood transfusions in severe disease; parenteral nutrition or defined enteral formulas—effective as primary therapy in CD, although high relapse rate when oral feeding is resumed; should not replace drug therapy; important role in preoperative preparation of malnourished pt; emotional support (Fig. 148-1).

SULFASALAZINE AND AMINOSALICYLATES: Active component of sulfasalazine is 5-aminosalicylic acid (5-ASA) linked to sulfapyridine carrier; useful in colonic disease of mild to moderate severity (1-1.5 g PO qid); efficacy in maintaining remission demonstrated only for UC (500 mg PO qid). Toxicity (generally due to sulfapyridine component): dose related—nausea, headache, rarely hemolytic anemia—may resolve when drug dose is lowered; idiosyncratic—fever, rash, neutropenia, pancreatitis, hepatitis, etc.; miscellaneous—oligospermia. Newer aminosalicylates are as effective as sulfasalazine but with fewer side effects. Enemas containing 4 g of 5-ASA (mesalamine) may be used in distal UC, one nightly retained qhs until remission, then q2hs or q3hs. Suppositories containing 500 mg of 5-ASA may be used in proctitis.

GLUCOCORTICOIDS: Useful in severe disease and ileal or ileocolonic CD. Prednisone, 40-60 mg PO qd, then taper; IV hydrocortisone, 100 mg tid or equivalent, in hospitalized pts; IV adrenocorticotropic hormone drip (120 U qd) may be preferable in first attacks of UC. Nightly hydrocortisone retention enemas in proctosigmoiditis. Numerous side effects make long-term use problematic.

IMMUNOSUPPRESSIVE AGENTS:Azathioprine, 6-mercaptopurine—50 mg PO qd up to 2.0 or 1.5 mg/kg qd, respectively. Useful as steroid-sparing agents and in intractable or fistulous CD (may require 2- to 6-month trial before efficacy seen). Toxicity—immunosuppression, pancreatitis, ?carcinogenicity. Avoid in pregnancy.

METRONIDAZOLE Appears effective in colonic CD (500 mg PO bid) and refractory perineal CD (10-20 mg/kg PO qd). Toxicity—peripheral neuropathy, metallic taste, ?carcinogenicity. Avoid in pregnancy. Other antibiotics (e.g., ciprofloxacin 500 mg PO bid) may be of value in terminal ileal and perianal CD, and broad-spectrum IV antibiotics are indicated for fulminant colitis and abscesses.

OTHERS: Cyclosporine (potential value in a dose of 4 [mg/kg]/d IV for 7-14 days in severe UC and possibly intractable Crohn's fistulas); experimental—tacrolimus, methotrexate, chloroquine, fish oil, nicotine, others. Infliximab (monoclonal antibody to tumor necrosis factor [TNF]) 5 mg/kg IV induces responses in 65% (complete in 33%) of CD pts refractory to 5-ASA, glucocorticoids, and 6-mercaptopurine. In UC, 27-49% of pts respond.

Adalimumab is a humanized version of the anti-TNF antibody that is less likely to elicit neutralizing antibodies in the pt. Pegylated versions of anti-TNF antibody may be used once monthly.

Natalizumab is an anti-integrin antibody with activity against CD, but some pts develop progressive multifocal leukoencephalopathy. Vedolizumab is specific for α4β7 integrin and is more gut selective in its effects.

SURGERY UC: Colectomy (curative) for intractability, toxic megacolon (if no improvement with aggressive medical therapy in 24-48 h), cancer, dysplasia. Ileal pouch—anal anastomosis is operation of choice in UC, but contraindicated in CD and in elderly. CD: Resection for fixed obstruction (or stricturoplasty), abscesses, persistent symptomatic fistulas, intractability.

For a more detailed discussion, see Friedman S, Blumberg RS: Inflammatory Bowel Disease, Chap. 351, p. 1947, in HPIM-19.