CYCLOSPORINE FOR THE TREATMENT OF FULMINANT ULCERATIVE-COLITIS IN CHILDREN - IMMEDIATE RESPONSE, LONG-TERM RESULTS, AND IMPACT ON SURGERY

PURPOSE: Emergency surgery for fulminant colitis is often complicated by high-dose steroid therapy, poor nutrition, and psychologic maladjus tment. Cyclosporine is effective for fulminant ulcerative colitis in a dults, resulting in avoidance of immediate surgery in 75 percent of pa tients and a 55 percent long-term remission rate. Over the last five y ears, we studied the effectiveness of cyclosporine in children with fu lminant colitis. METHODS: Fourteen patients with ulcerative colitis (a ge, 7-20 years) received cyclosporine after satisfying the following c riteria: 1) greater than five bloody diarrheal stools per day; 2) seve re abdominal pain; 3) no improvement after ten days of bowel rest, 4) intravenous methylprednisolone (1-2 mg/kg/day); and 5) parenteral nutr ition. Treatment was begun with oral cyclosporine (4.6-9.6 mg/kg/day), and the dose was adjusted to achieve whole blood trough levels measur ed with a monoclonal radioimmunoassay between 150 and 300 ng/ml. If im proved, 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 t hree or less soft stools per day, and had no pain. One did not respond after ten days and underwent an ileal pouch-anal anastomosis procedur e. Two patients elected surgery after 20 days of therapy and a partial response. Of 11 patients who left the hospital, 4 had recurrent sympt oms after 2 to 11 months of taking therapeutic doses of cyclosporine a nd 3 flare ups while weaning from cyclosporine after 4 to 8 months. Th ree patients have been weaned from cyclosporine after 8 to 13 months a nd have remained in remission from six months to five years. One patie nt is about to complete a six-month course of cyclosporine. Overall te n (72 percent) have undergone surgery, including 7 of 11 who responded initially to cyclosporine and left the hospital. Weight (P < 0.001), albumin (P < 0.01), erythrocyte sedimentation rate (P > 0.05), and pre dnisone dose (P < 0.001) improved significantly in the seven patients on cyclosporine who responded initially, left the hospital, and subseq uently underwent surgery. CONCLUSIONS: Cyclosporine is effective in ac hieving clinical remission in 80 percent of children with refractory f ulminant colitis; however, within one year, most initial responders wi ll require colectomy because of a flare up of the disease. In a majori ty of patients, the role of cyclosporine therapy is to rapidly amelior ate symptoms and prevent precipitous colectomy, improve nutrition and psychologic adaptation, and reduce the steroid dose lending to surgery in a well-prepared patient.