Invited Commentary

Abstract

Protein-losing enteropathy (PLE) is an enigmatic ailment that strikes children and young adults after a Fontan operation. Over the past 20 years myriad treatments have been proposed ranging from ameliorating the circulatory failure of the Fontan circuit through fenestration creation to the use of medications such as steroidal agents, unfractionated heparin, and high-dose spironolactone. For each of these strategies, great initial enthusiasm has ultimately been tempered by the finding of only modest utility with limited long-term efficacy. Data suggest that inflammation may play an important role in PLE after a Fontan operation. On theoretical grounds, oral controlled-release budesonide is an ideal intestinal antiinflammatory agent. Unlike prednisone, it has high enteric affinity and is 90% metabolized at first pass through the liver, theoretically reducing the risk of steroid-related systemic side effects. Borrowing from a broad experience in children with inflammatory bowel disease, we reported in The Annals of Thoracic Surgery in 2010 on the successful use of budesonide in raising serum protein levels in patients treated at a median age of 15 years (range, 4 to 29 years). John and colleagues [1John A.S. Driscoll D.J. Warnes C.A. Phillips S.D. Cetta F. The use of oral budesonide in adolescents and adults with protein-losing enteropathy after the Fontan operation.Ann Thorac Surg. 2011; 92: 1451-1456Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar] from the Mayo Clinic now report their experience with budesonide in a group of patients treated at a median age of 20 years (range, 16 to 32 years) They found a high rate of steroid-related side effects as well as a high rate of treatment failure. The high rate of side effects likely reflects indolent progressive hepatic dysfunction related to time after Fontan operation. The high failure rate suggests a resistance to disease treatment in those with long-standing illness, perhaps related to chronic changes in the gut lumen over time. The growing experience with oral budesonide as treatment for PLE provides a number of lessons. There is clearly a subgroup of patients who respond well, with the ability to wean to low doses with improvement in symptoms and quality of life, and a subgroup that does not respond. Budesonide is a potentially useful agent but should be tried with caution. If serious side effects are noted, or no response is seen within a limited time (3 to 6 months), weaning and discontinuation is indicated. More effective strategies for this debilitating disease await a clearer fundamental understanding of the mechanism of the disorder, which to date continues to elude us. The Use of Oral Budesonide in Adolescents and Adults With Protein-Losing Enteropathy After the Fontan OperationThe Annals of Thoracic SurgeryVol. 92Issue 4PreviewApproximately 5% to 15% of patients develop protein-losing enteropathy (PLE) after the Fontan operation. Oral controlled release (CR) budesonide has been used as a treatment strategy, but its use in the older Fontan population has not been described. Full-Text PDF