Chronic Diarrhea Resistant to Treatment
This Brief Consultation column originally was published in the May 1990 issue of Consultant. The original letter was sent in from HN Flora, Jr, DO, from Nowata, Oklahoma, and was responded to by Richard G. Farmer, MD, from The Cleveland Clinic Foundation in Cleveland, Ohio.
Read the Editorial based on this article, written by Consultant Board Member Dr Alan Lucerna here.
Citations:
Flora Jr HN. Chronic diarrhea resistant to treatment [letter]. Consultant. 1990;30(5):43.
Farmer RG. Chronic diarrhea resistant to treatment [reply]. Consultant. 1990;30(5):43.
Letter:
A 48-year-old woman came to me on May 31, 1989, with a history of diarrhea for more than a month, with no response to the usual OTC medication. At that time, she reported having 10 to 15 stools daily.
Before developing diarrhea, this patient had been under long-term treatment for degenerative joint disease and mitral valve prolapse with intermittent runs of supraventricular tachycardia. Her medical regimen consisted of naproxen, 500 mg bid; propranolol, 80 mg bid; and chlordiazepoxide/amitriptyline, 1 tablet (10/25 mg) qid.
Her initial evaluation consisted of stool cultures (negative); blood chemistry (not remarkable); upper GI series (tertiary contractions in the esophagus, otherwise normal); lower GI series (irritability and spasm throughout the colon with evidence suggesting edema of the mucosa in the lower colon); and 60-cm sigmoidoscopic examination (grossly edematous, red, inflamed colon with a considerable amount of mucus). At that time, the patient was given sulfasalazine, 500 mg qid; prednisone, 20 mg/d; and misoprostol, 200 µg qid, and referred to a gastroenterologist.
The gastroenterologist did a colonoscopic examination with biopsy. His diagnosis was a mild, nonspecific, distal colitis. He recommended weaning from corticosteroids and discontinuing sulfasalazine, and he prescribed dicyclomine.
The diarrhea continued, and the gastroenterologist restarted the prednisone at high doses (60 mg/d), restarted the sulfasalazine (1 g qid), and added a diphenoxylate-atropine combination. In addition to the continuing diarrhea, on June 19 the patient developed severe upper abdominal pain, nausea, and vomiting and was hospitalized. Esophagogastroduodenoscopy revealed diffuse, mild gastritis secondary to use of nonsteroidal anti-inflammatory drugs and/or corticosteroids. The corticosteroid and naproxen were discontinued. The diarrhea persisted.
Repeat sigmoidoscopy was done on July 6 and revealed an improvement in the colon with decreased erythema and inflammation. At that time, the report of colon biopsy was “colorectal mucosa exhibiting acute and chronic inflammation with cryptitis with admixed fibrinopurulent debris.” In addition to sulfasalazine, dicyclomine, and now loperamide, a 6-week course of cortisone enemas was prescribed, which effected little improvement.
This woman continues to experience tenesmus, has up to 6 stools a day, is very weak, and is anorectic. She is not anemic, and there has been no grossly bloody stool. Her present medical regimen consists of loperamide, 8 capsules a day; folic acid; sulfasalazine, 1 g qid; propranolol, 160 mg/d; naproxen, 1 g/d; and chlordiazepoxide/amitriptyline, 1 tablet (10/25 mg) qid. We tried to stop the propranolol and switch to verapamil, but she experienced tachycardia (up to 140 beats/min) and was placed back on propranolol. We discontinued naproxen, but the degenerative bone disease became disabling, and the NSAID was restarted.
HN Flora, Jr, DO
Nowata, Oklahoma
Reply:
My assessment is that this is a form of ulcerative colitis, predominantly affecting the distal colon. The general approach should be relatively long-term treatment with sulfasalazine (for 6 to 12 months) and intermittent use of prednisone (probably 40 mg/d or less, with appropriate tapering depending on response).
Since your approach has been somewhat similar to this recommendation, an alternative might be hospitalization with use of hyperalimentation for 2 or 3 weeks. If that does not improve the situation, creation of a temporary ileostomy might be necessary. That sounds drastic, but in some patients the sequence of sulfasalazine to prednisone to hospitalization to hyperalimentation to ileostomy does take place, despite the fact that inflammation does not seem severe in the face of the symptoms.
Tenesmus with presumed small-volume diarrhea typically is associated with distal colon inflammation, and at times it can be very difficult to treat. As a side issue, the use of cimetidine or a similar agent for the gastritis is frequently necessary and does not, in my experience, preclude administration of steroids in a situation such as this.
The use of topical steroids and particularly cortisone enemas is frequently beneficial, and it is discouraging that these did not appear to be effective. Although it is perhaps too soon to determine, the use of 5-ASA enemas may be helpful as ad junctive treatment. 5-ASA appears to be the active portion of sulfasala zine and has been used therapeutically on that basis in the recent past. Its role remains to be fully evaluated. I recognize that this is a difficult case, but I can tell you it is not necessarily unusual.
Richard G. Farmer, MD
The Cleveland Clinic Foundation
Cleveland, Ohio