The main aims of therapy for inflammatory bowel disease (Crohn disease) in children and adolescents are (1) the induction and maintenance of remission, (2) the correction of nutrient deficits and (3) the restoration of growth and maturation. These goals are reached with the use of a combination of therapeutic methods, including pharmacologic agents, nutritional and psychological support, and surgical intervention. The commonly used drugs sulfasalazine, corticosteroids and metronidazole have all been shown to be safe and efficacious when given to children. Newer steroid preparations that are rapidly degraded either in the target tissue or elsewhere are being studied. Of these, budesonide currently shows promise as an efficacious drug with few side effects, but its use in children needs further study. Newer 5-amino-salicylate preparations such as Asacol have been shown to be effective in children, but the number of patients studied is small. Immunomodulatory drugs such as azathioprine and 6-mercaptopurine appear to be safe and efficacious for children; cyclosporine has been used infrequently to treat refractory Crohn disease in children. The use of other agents such as methotrexate, tacrolimus, monoclonal antibodies to cytokines, antibiotics and specific dietary products such as fish oils have not been intensively studied in children with Crohn disease. Nutritional therapy remains a mainstay of treatment because it corrects nutritional deficits, replaces losses and stimulates growth.
BackgroundGrowth failure frequently complicates Crohn's disease in childhood. Abnormalities in the growth hormone (GH)/insulin-like growth factor-1 axis may occur. The effects of administered GH on growth have not been studied previously in a randomized trial.
Abstract: Tacrolimus is a macrolide agent that is now the primary immunosuppressant used in prevention of graft rejection in transplant recipients. It has been found to be superior to cyclosporine (CSA) for rescue therapy as well as for earlier weaning of steroids. Both tacrolimus and CSA share similar toxicity profiles; however, their gastrointestinal side effects have received little attention. We report three cases of eosinophilic colitis in liver transplant recipients, maintained on tacrolimus as immunosuppressive medication post‐liver transplantation. These patients also had high serum immunoglobulin (Ig)E levels, eosinophilia and IgE‐positive radioallergosorbent test for milk proteins. The colitis appeared to be mediated by food allergies. Each patient had symptomatic improvement following reduced immunosuppression and an appropriately restricted diet. We conclude that tacrolimus may play a role in the initiation of food allergies, leading to eosinophilic colitis. More studies are needed in a controlled setting to identify the prevalence of similar findings among other pediatric liver transplant recipients.
108 FK506 is a macrolide immunosuppressive that is increasingly being used for prevention of graft rejection in transplant recipients. It shares similar toxicity profiles with cyclosporine (CSA). However, very little is reported about its GI side effects. We retrospectively identified 3 patients who were started on FK506 post OLT and developed biopsy proven colitis, thought to be allergic in nature. Case 1 underwent OLT after a failed Kasai procedure for biliary atresia; 20 mos later, he developed guaiac positive diarrhea, neg for pathogens. Colonoscopy revealed focal colitis. He was also noted to have peripheral eosinophilia (24%) and positive RAST for milk protein. CSA was substituted for FK506 with resolution of symptoms on a milk restricted diet. Case 2 received OLT for Alagille syndrome at 33 mos of age (CSA primary therapy). FK506 was started a month later for mild rejection. He developed diarrhea 23 mos later, negative for pathogens. Flexible sigmoidoscopy revealed active as well as chronic inflammation. He had mild eosinophilia but normal IgE levels. A month later he developed PTLD along with marked eosinophilia (32%) and was switched to CSA as well as a milk restricted diet with resolution of symptoms. Case 3 underwent OLT for fulminant hepatic failure of unknown etiology, followed 4 mos later by BMT for aplastic anemia. 17 mos after OLT, he developed guaiac positive diarrhea, negative for pathogens. Peripheral eosinophilia (∼9%) was also found. Colonoscopy revealed increased mucosal eosinophils without activity or evidence of GVHD. RASTs were positive for milk, wheat, eggs, and oats. He was placed on a restricted diet but persistence of symptoms necessitated switch to CSA with subsequent resolution of symptoms. Conclusions: In these patients, FK506 was associated with the induction of allergic colitis. Therapy was facilitated by discontinuation of FK506 and switch to CSA. More studies are needed in a controlled setting to identify the prevalence of similar findings among pediatric liver transplant recipients.
Summary The aim of this study was to assess whether in steroid-resistant patients with pediatric inflammatory bowel disease (IBD) a combination of cyclosporine and azathioprine (or 6-mercaptopurine) could induce remission and subsequently permit maintenance on azathioprine/6-mercaptopurine as the sole immunosuppressive agent. Two boys and six girls (six with ulcerative colitis and two with Crohn's disease; ages 3-17 years) received 100-200 μg/kg/day cyclosporine intravenously and then 4-10 mg/kg/day orally. Doses were adjusted to achieve trough serum cyclosporine levels of 100-200μ/L (Abbott's TDX assay). Seven of the eight patients received azathioprine/6-mercaptopurine, and all were given a 5-aminosalicylate preparation and corticosteroids. The latter drugs were continued and then tapered off as clinical status allowed. Cyclosporine was continued for 3-10 months in those who responded. In seven of eight patients, there was a rapid clinical response; one patient showed a transient response, but recurrent bleeding led to total colectomy 9 days after starting cyclosporine. Of the seven responders, three were able to discontinue prednisone and cyclosporine and are doing well on azathioprine at long-term follow-up (2-5 years). One who did not receive azathioprine/6-mercaptopurine maintained remission for 2 years after cyclosporine was stopped, one experienced a disease flare-up 5 months after start of cyclosporine treatment and required colectomy, one who did not tolerate 6-mercaptopurine had a flare-up during cyclosporine tapering and underwent surgery at 6 months, and one started to flare up with cyclosporine tapering at 6 months and was scheduled for surgery. No significant complications of treatment were observed. Seven patients had an initial response and four of them have so far not required surgery. These preliminary findings suggest that azathioprine/6-mercaptopurine can be used safely to maintain cyclosporine-induced remission in children with IBD.
