Cyclosporine for the treatment of fulminant ulcerative colitis in children
1995
PURPOSE: Emergency surgery for fulminant colitis is often complicated by high-dose steroid therapy, poor nutrition, and psychologic maladjustment. Cyclosporine is effective for fulminant ulcerative colitis in adults, resulting in avoidance of immediate surgery in 75 percent of patients and a 55 percent long-term remission rate. Over the last five years, we studied the effectiveness of cyclosporine in children with fulminant colitis. METHODS: Fourteen patients with ulcerative colitis (age, 7–20 years) received cyclosporine after satisfying the following criteria: 1) greater than five bloody diarrheal stools per day; 2) severe abdominal pain; 3) no improvement after ten days of bowel rest, 4) intravenous methylprednisolone (1–2 mg/kg/day); and 5) parenteral nutrition. Treatment was begun with oral cyclosporine (4.6–9.6 mg/kg/day), and the dose was adjusted to achieve whole blood trough levels measured with a monoclonal radioimmunoassay between 150 and 300 ng/ml. If improved, patients were discharged on oral cyclosporine, prednisone, and a regular diet. RESULTS: Eleven of 14 patients (78 percent) responded within two to nine days and were able to consume a normal diet, had three or less soft stools per day, and had no pain. One did not respond after ten days and underwent an ileal pouch-anal anastomosis procedure. Two patients elected surgery after 20 days of therapy and a partial response. Of 11 patients who left the hospital, 4 had recurrent symptoms after 2 to 11 months of taking therapeutic doses of cyclosporine and 3 flare ups while weaning from cyclosporine after 4 to 8 months. Three patients have been weaned from cyclosporine after 8 to 13 months and have remained in remission from six months to five years. One patient is about to complete a six-month course of cyclosporine. Overall ten (72 percent) have undergone surgery, including 7 of 11 who responded initially to cyclosporine and left the hospital. Weight (P 0.05), and prednisone dose (P<0.001) improved significantly in the seven patients on cyclosporine who responded initially, left the hospital, and subsequently underwent surgery. CONCLUSIONS: Cyclosporine is effective in achieving clinical remission in 80 percent of children with refractory fulminant colitis; however, within one year, most initial responders will require colectomy because of a flare up of the disease. In a majority of patients, the role of cyclosporine therapy is to rapidly ameliorate symptoms and prevent precipitous colectomy, improve nutrition and psychologic adaptation, and reduce the steroid dose leading to surgery in a well-prepared patient.
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