Managing the glucocorticoid dependent inflammatory bowel disease patient.

At this time, standard therapy for treatment of inflammatory bowel disease includes the use of glucocorticoids for moderate to severe Crohn's disease, severe ulcerative colitis, and moderate ulcerative colitis failing mesalamine. Although the majority of patients will have clinical improvement with glucocorticoids, a substantial minority of patients will later flare with attempts to withdraw therapy. Given the numerous potential side effects associated with glucocorticoids, every effort should be made to switch these patients to a less toxic medication. Historically, the most reliable agents have been azathioprine or 6-mercaptopurine. Infliximab is a relatively new medication but would be expected to be beneficial for weaning glucocorticoids for Crohn's disease patients. Methotrexate is another alternative for Crohn's disease. Budesonide and CDP571 are still in developmental phases but likely will be helpful in managing this patient population. Mesalamine, cyclosporine, mycofenalate mofetil, and thalidomide have less data available to support their use but may be helpful for some patients. 6-Thioguanine may be an alternative to patients who do not tolerate 6-mercaptopurine or azathioprine.

Tolerance of nonsteroidal antiinflammatory drugs in patients with inflammatory bowel disease.

OBJECTIVE: We sought to examine whether use of nonsteroidal antiinflammatory drugs (NSAIDs) in an outpatient inflammatory bowel disease (IBD) population is associated with an increased likelihood of active disease. METHODS: We reviewed records of initial outpatient visits of IBD patients to the principal author from June 1995 to December 1997, with regard to use of aspirin and other NSAIDs and disease activity. RESULTS: Of 40 Crohn's patients seen with active disease, three (7.5%) were using NSAIDs; 14 of 72 (19.4%) Crohn's patients seen with inactive disease were using NSAIDs. Fifty-eight ulcerative colitis patients were seen with active disease, with eight (13.7%) using NSAIDs. Among 21 UC patients initially seen while in remission, five (23.8%) were using NSAIDs. CONCLUSIONS: Among this group of outpatients, NSAID use was not associated with a higher likelihood of active IBD. NSAID use in IBD deserves further study before recommending that patients refrain from their use under all circumstances.

Short- and long-term follow-up of treatment for lymphocytic and collagenous colitis.

Collagenous colitis and lymphocytic colitis cause chronic watery diarrhea. Multiple therapies have been found to improve symptoms but there have been few long-term follow-up studies. Our goal was to obtain long-term clinical follow-up on a cohort of patients with independently confirmed typical histopathologic changes. Pathology slides from 32 cases of collagenous or lymphocytic colitis patients from 1988-1992 were independently reviewed. Twenty-five cases were confirmed by both groups of pathologist as collagenous or lymphocytic colitis. For these 25 patients, charts were reviewed and telephone follow-up interviews were performed in 1992 and 1995. Seven of 32 (22%) of the original cases were not confirmed on independent pathologic interpretation. A 15.8% discordance rate was found between the different groups of pathologists. Patient demographics were similar to previously published reports except one-half of our patients had diarrhea of only 6 months or less. Eighty-one percent of patients receiving 5-ASA agents reported improvement as well as 100% of those receiving prednisone. At 23 month follow-up 86% of patients reported improvement in diarrhea and only 32% required routine medications. At 47 month follow-up all patients reported improved diarrhea and only 29% required routine medications. Collagenous and lymphocytic colitis can sometimes be identified in patients with relatively brief duration diarrhea. Clinical parameters and response to therapy are similar for collagenous or lymphocytic colitis. Most patients with lymphocytic and collagenous colitis improve with therapy such as 5-ASA preparations or steroids. Over a follow-up period of several years, most patients have improvement in diarrhea and generally do not require maintenance medications. Independent pathologic confirmation of the diagnosis should be obtained in patients not responding to therapy.

The effect of ursodeoxycholic acid on the florid duct lesion of primary biliary cirrhosis.

The frequency with which florid duct lesions are seen in needle-biopsy specimens of the liver was assessed in patients with primary biliary cirrhosis (PBC) enrolled in a 2-year randomized, double-blind, placebo-controlled trial of ursodeoxycholic acid (UDCA) versus placebo. Paired biopsy specimens obtained at entry and after 2 years on medication were reviewed blindly and mostly simultaneously by a panel of 5 hepatopathologists who, earlier, had characterized the florid duct lesion, which has been well described in the pathology literature. Florid duct lesions at entry were identified in approximately 36%. Patients with earlier disease showed florid duct lesions much more frequently than those with more advanced disease. The prevalence of florid duct lesions in 60 patients receiving placebo medication fell from 38.3% to 21.7%, P =. 025, over the period of 2 years. The prevalence of florid duct lesions also decreased in the 55 patients receiving UDCA, from 32.7% to 18.2%, P =.046. The prevalences of these lesions in the placebo and UDCA patients at entry and at 2 years were not significantly different from each other. The findings suggest that UDCA does not prevent ongoing bile duct destruction in patients with PBC. Instead, they support the impression that UDCA exerts its beneficial effects by protecting against the consequences of bile duct destruction.

Biliary bile acids in primary biliary cirrhosis: effect of ursodeoxycholic acid.

Bile acid composition in fasting duodenal bile was assessed at entry and at 2 years in patients with primary biliary cirrhosis (PBC) enrolled in a randomized, double-blind, placebo-controlled trial of ursodeoxycholic acid (UDCA) (10-12 mg/kg/d) taken as a single bedtime dose. Specimens were analyzed by a high-pressure liquid chromatography method that had been validated against gas chromatography. Percent composition in bile (mean +/- SD) for 98 patients at entry for cholic (CA), chenodeoxycholic (CDCA), deoxycholic (DCA), lithocholic (LCA), and ursodeoxycholic (UDCA) acids, respectively, were 57.4 +/- 18.6, 31.5 +/- 15.5, 8.0 +/- 9.3, 0.3 +/- 1.0, and 0.6 +/- 0.9. Values for CA were increased, whereas those for CDCA, DCA, LCA, and UDCA were decreased when compared with values in normal persons. Bile acid composition of the major bile acids did not change after 2 years on placebo medication. By contrast, in patients receiving UDCA for 2 years, bile became enriched with UDCA on average to 40.1%, and significant decreases were noted for CA (to 32.2%) and CDCA (to 19.5%). No change in percent composition was observed for DCA and LCA. Percent composition at entry and changes in composition after 2 years on UDCA were similar in patients with varying severity of PBC. In patients whose bile was not enriched in UDCA (entry and placebo-treated specimens), CA, CDCA, DCA, and the small amount of UDCA found in some of these specimens were conjugated to a greater extent with glycine (52%-64%) than with taurine (36%-48%). Treatment with UDCA caused the proportion of all endogenous bile acids conjugated with glycine to increase to 69% to 78%, while the proportion conjugated with taurine (22%-31%) fell (P <.05). Administered UDCA was also conjugated predominantly with glycine (87%).

Management of inflammatory bowel disease.

Patients with an inflammatory bowel disease, such as ulcerative colitis or Crohn's disease, have recurrent symptoms with considerable morbidity. Patient involvement and education are necessary components of effective management. Mild disease requires only symptomatic relief and dietary manipulation. Mild to moderate disease can be managed with 5-aminosalicylic acid compounds, including olsalazine and mesalamine. Mesalamine enemas and suppositories are useful in treating proctosigmoiditis. Antibiotics such as metronidazole may be required in patients with Crohn's disease. Corticosteroids are beneficial in patients with more severe symptoms, but side effects limit their use, particularly for chronic therapy. Immunosuppressant therapy may be considered in patients with refractory disease that is not amenable to surgery. Inflammatory bowel disease in pregnant women can be managed with 5-aminosalicylic acid compounds and corticosteroids. Since longstanding inflammatory bowel disease (especially ulcerative colitis) is associated with an increased risk of colon cancer, periodic colonoscopy is warranted.

Idiopathic midesophageal stricture: a new cause of dysphagia in a patient with AIDS.

A number of disorders may result in the complaint of dysphagia in HIV-infected patients. These include fungal, viral, bacterial, parasitic, medication-induced, and idiopathic lesions in the esophagus. In the current case, a 32-year-old man with advanced HIV infection had recurrent bouts of esophageal stricture. No ulcer was associated with this stricture. No infectious causes of the stricture could be determined. The patient required multiple upper endoscopies and dilatations for treatment of this stricture and subsequently had a food impaction. This is the first case in the medical literature of an idiopathic stricture in the middle portion of the esophagus in an HIV-infected patient. We postulate that this lesion may have been caused by the patient's medications. Esophageal strictures should be considered in HIV-infected patients with severe dysphagia or food-bolus impactions of the esophagus.

Serum electrolyte abnormalities secondary to Fleet's Phospho-Soda colonoscopy prep. A review of three cases.

The authors report three cases of adverse reactions to commonly used lavage solutions generally believed harmless.

Current medical therapy for inflammatory bowel disease.

Traditional medical therapy for inflammatory bowel disease (IBD) includes corticosteroids and sulfasalazine. In recent years, several mesalamine derivatives of sulfasalazine have become available. These allow delivery of increased dosages of active medication with minimal side effects. Newer steroid preparations, all investigational at this point, likely will offer efficacy similar to that of prednisone but with an improved side effect profile. Immunosuppressive agents, including 6-mercaptopurine, azathioprine, and likely also methotrexate, are beneficial in treating refractory IBD, particularly in patients with chronic steroid dependence. Cyclosporine has been shown to be remarkably effective in delaying colectomy for severe ulcerative colitis, but its long-term role remains uncertain.

Prospective, randomized, endoscopic-blinded trial comparing precolonoscopy bowel cleansing methods.

PURPOSE: Recent reports have suggested that precolonoscopy bowel preparation is easier to tolerate if a small volume solution is used. Therefore, the aim of this study was to compare three oral solutions for colonoscopy to determine any changes in either patient compliance or cleansing ability. METHODS: Four hundred fifty patients were prospectively randomized to receive either a standard 4-liter polyethylene glycol solution, a newer sulfate-free 4-liter polyethylene glycol solution, or a 90-ml oral sodium phosphate preparation. Before and after bowel preparation all patients were weighed, and serum electrolytes as well as phosphate, magnesium, calcium, and osmolarity were measured. In addition, a detailed questionnaire was used to assess side effects and patient satisfaction. Endoscopists blinded to the type and quantity of preparation used scored the type of residual stool and the percentage of bowel wall visualized for each segment of colon and for the overall examination. Nurses recorded all procedure times as well as the quantity of irrigation and aspiration. RESULTS: Four hundred twenty-two age-matched and sex-matched patients completed all phases of the trial. There were no clinically significant changes in weight or in any biochemical parameters. There was, however, asymptomatic hyperphosphatemia in the sodium phosphate group (P < 0.01). The length of time to the cecum was similar for all three groups, with a higher volume of fluid suctioned for sodium phosphate (P < 0.01). Overall, endoscopists scored sodium phosphate as "excellent" or "good" in 90 percent vs. 70 percent and 73 percent after the polyethylene glycol or sulfate-free lavage, respectively (P < 0.01). Particulate or solid stool was found in all segments of the colon more frequently after both large volume preparations than after sodium phosphate (P < 0.05). There were no significant differences in the frequency or intensity of any of the 11 side effects questioned. Eighty-three percent of the patients who received the sodium phosphate preparation stated they would take this same preparation again, vs. only 19 percent and 33 percent for polyethylene glycol and the sulfate-free lavage, respectively (P < 0.01). CONCLUSION: The smaller volume oral sodium phosphate was not associated with any clinically significant problem, caused no increase in the incidence of side effects, was preferred by patients, and was more effective in colonic cleansing. However, the hyperphosphatemia seen may limit its use in patients with impaired renal function.