LABORATORIOS FARMACEÚTICOS

suggested by anemia, hypoalbuminemia, and an increased sedimentation rate.

2. Evaluation of exudative diarrhea consists of a

complete blood cell count, serum albumin, total protein, erythrocyte sedimentation rate, electro- lyte measurement, Entamoeba histolytica anti- body titers, stool culture, Clostridium difficile antigen test, ova and parasite testing, and flexible sigmoidoscopy and biopsies. References, see page 282.

Inflammatory Bowel Disease

Ulcerative colitis is limited to the rectum and colon. Crohn's disease may involve both the small and the large bowel, but 15% to 25% of cases are isolated to the colon. Both Crohn's disease and ulcerative colitis can follow an active and remitting course and have a highly variable response to therapy.

I. Clinical presentation

A. Crohn’s disease is a chronic, transmural,

granulomatous disorder that can involve any segment of gastrointestinal tract from the mouth to the anus. In the bowel it may affect multiple distinct segments, with normal intervening bowel. Crohn’s disease also may be complicated by intestinal strictures, fistulas, and perianal fistulas. The clini- cal presentation of Crohn’s disease ranges from intestinal obstruction, to bloody or nonbloody diarrhea, to malabsorption.

B. Ulcerative colitis is a nongranulomatous inflam-

matory condition that always starts in the rectum and extends proximally throughout the colon in a continuous and confluent fashion, never involving the small bowel. The clinical presentation of ulcer- ative colitis is more uniform than that of Crohn’s disease and includes rectal bleeding or bloody diarrhea. In addition to gastrointestinal symptoms, extraintestinal manifestations can occur and may involve the skin (eg, erythema nodosum, pyoderma gangrenosum), joints (sacroiliitis, ankylosing spondylitis, and peripheral arthritis), eyes (iritis and uveitis), and liver (sclerosing cholangitis). Extraintestinal manifestations are due to the re- lease of bacterial antigens from the colonic lumen.

C. Differential diagnosis. In patients with new-onset

bloody diarrhea and abdominal cramps, an infec- tious cause must first be ruled out. In addition to routine cultures, cultures for Clostridium difficile, ova and parasites, and hemorrhagic Escherichia coli should be done. Colonic ischemia presents with symptoms similar to those of IBD--abdominal cramps, rectal bleeding, and diarrhea--and should be a consideration in older patients. Nonsteroidal anti-inflammatory drugs can also cause colonic ulcerations that mimic colonic Crohn’s disease.

II. Induction therapy

A. Mild-to-moderate Crohn’s disease

1. Patients with mild to moderate colonic Crohn’s

disease may be managed successfully with 5-ASA products, such as sulfasalazine (Azulfidine), 1 g two to four times daily, which produces remission in about 50%.

moiety attached to 5-ASA. It is activated in the colon by colonic bacteria that releases sulfapyridine, which is then absorbed. The 5-ASA remains in the colon. Side effects include nausea, gastrointestinal upset, rash, headache, and reversible male infertility. Rare hypersensi- tivity reactions include hemolytic anemia, neutropenia, and hepatitis.

3. For patients with colonic Crohn’s disease who

are unable to tolerate sulfasalazine or who are allergic to sulfa drugs, sulfa-free 5-ASA prod- ucts have been developed. Olsalazine (Dipentum), 500 mg two or three times daily, and balsalazide (Colazal), 2.25 g three times daily, work exclusively in the colon, whereas the mesalamine preparations--Asacol, 800 to 1,600 mg three or four times daily, and Pentasa, 1 g four times daily--are released in the small bowel and the colon.

4. Antibiotics also have been used in the treatment

of colonic Crohn’s disease. Metronidazole (Flagyl), 250 to 500 mg three times daily, has been shown to be beneficial in colonic Crohn’s disease as well as in Crohn’s in patients with perianal abscesses and fistulas. Ciprofloxacin (Cipro) has been used as an alternative to metronidazole for both colonic and perianal Crohn’s disease.

B. Mild-to-moderate ulcerative colitis

1. Ulcerative colitis with fewer than six loose

bowel movements per day, with or without blood, and without significant weight loss or anemia is considered to be mild-to-moderate disease. In this setting, 5-ASA drugs such as sulfasalazine or Asacol are often used as pri- mary therapy. Onset of action is usually within 1 week, but peak effect is not reached for 3 to 6 weeks.

2. For patients with isolated proctitis, corticosteroid

(Anusol) or mesalamine (Canasa) suppository given once or twice a day is usually sufficient therapy. When ulcerative colitis extends beyond the rectum, corticosteroid foam (Cortifoam, ProctoFoam) or enema (Cortenema) or mesalamine enema (Rowasa) may be used nightly.

C. Moderate-to-severe Crohn’s disease 1. Patients with moderate to severe Crohn’s dis-

ease often present with severe abdominal pain, diarrhea, weight loss, fever, and symptoms of obstruction.

2. Budesonide (Entocort), 9 mg once daily, is

approved for the treatment of ileal and ileocecal Crohn’s disease. Although prednisone and budesonide are equally efficacious, budesonide’s extensive first-pass metabolism through the liver and high affinity for the glucocorticoid receptor in the small bowel.

3. Another novel therapy for Crohn’s disease is

infliximab (Remicade), which is approved for induction of remission. Infliximab is a monoclonal antibody to tumor necrosis factor alpha and is given intravenously. A single outpatient infusion of infliximab yielded a clinical response in up to 80%.

4. Methotrexate, 25 mg intramuscularly, has been

shown to be efficacious in a subgroup of ste- roid-dependent patients.

D. Moderate-to-severe ulcerative colitis 1. Patients presenting with moderate to severe

ulcerative colitis usually have more than six loose to watery bowel movements per day, often containing blood, along with abdominal cramps, weight loss, and anemia. Patients with ulcer- ative colitis may be treated with oral prednisone or intravenous therapy.If a severely ill patient fails to respond within 7 to 10 days, intravenous cyclosporine or colectomy should be consid- ered.

2. Cyclosporine. In a trial of patients with ulcer-

ative colitis refractory to corticosteroids, 83% responded to cyclosporine. Cyclosporine should be used as a transitional agent or bridge to longer-term therapy with an immunomodulating drug or to elective colectomy.

III. Maintenance therapy

A. Most of the drugs used for induction of remission

also may be used for maintenance therapy. Treat- ments include 5-ASA products, immunomodulators (6-mercaptopurine [Purinethol] and azathioprine [Imuran]), and infliximab. Corticosteroids, however, should almost never be used for long-term therapy.

B. For patients with Crohn’s disease or ulcerative

colitis refractory to prednisone therapy or who become prednisone-dependent, use of i m m u n o m o d u l a t i n g a g e n t s s u c h a s 6-mercaptopurine, 1.5 to 2 mg/kg per day, and its

prodrug azathioprine, 2 to 2.5 mg/kg per day, has proved beneficial. Infliximab has recently been shown to be efficacious in the maintenance of remission for Crohn’s disease.

Neurologic Disorders