Sections

Sections Pediatric Protein-Losing Enteropathy
Overview
Presentation
DDx
Workup
Treatment
Medication
Follow-up
References

Treatment

Medical Care

Therapeutic approaches for protein-losing enteropathy (PLE) depend on the underlying etiology. In PLE associated with primary intestinal lymphangiectasia or lymphatic obstruction, relieving the pressure in the lymphatic system decreases lymphatic flow and intestinal protein loss. Obstruction of lymphatics has been reported with structural heart disease, constrictive pericarditis, cardiomyopathy, and surgical repair of congenital heart disease. When losses from the intra-abdominal lymphatic system are the cause of PLE, removal of long-chain triglycerides from the diet decreases the pressure in the lacteals and the lymphatic circulation. Replacing fat in the diet with medium-chain triglycerides (MCTs) increases net fat absorption and the nutritional status of the patient. The use of MCT oil in these cases does not relieve any inflammation, but because MCT oil is not absorbed via the lymphatic system, it reduces the pressure of the lacteals. Fat soluble (ADEK) vitamin supplementation is required as their absorption is attenuated by the compromise in the lymphatic flow.

PLE that results after heart surgery (with increased pressure in the right side) is a known postoperative complication of the Fontan procedure that has been a challenge to the surgical procedure's long-term success. Multiple treatments have been used, including corticosteroids, heparin, and additional surgical intervention (baffle fenestration or heart transplantation).^[48]

As many as 13.4% of patients undergoing a Fontan procedure develop PLE within 10 years of surgery, and the mortality rate associated with this complication has been reported to be as high as 56% in 5 years.

The use of steroids has produced temporary clinical and pathological resolution of PLE.

A single-center retrospective review examined the use of budesonide, an oral steroid with extensive first pass metabolism, for 6 months or longer in Fontan-related PLE patients. This treatment was associated with significant symptomatic improvement and sustained increases in serum albumin but did not markedly change the ultimate outcome and was associated with significant side effects.^[49]

Heparin has also been reported to improve PLE in children after the Fontan procedure. Heparin is thought to possibly have a stabilizing effect on the capillary endothelium, reducing protein leakage into the extravascular space and gut lumen, although the precise mechanism of action is unknown. Although heparin has been successfully used to treat some patients with PLE that develops after the Fontan procedure, it is by no means the treatment of choice for all the etiologies of PLE.

A retrospective review of 42 patients with PLE following the Fontan procedure found that treatments used more frequently in survivors included spironolactone (68%), octreotide (21%), sildenafil (19%), and surgical intervention (71%).^[17]

Corticosteroids, including budesonide, have been used in patients with PLE associated with collagen vascular diseases, inflammatory bowel disease, heart surgery, and others. Sporadic case reports have documented the successful use of other agents such as cyclosporine for PLE. Immunosuppressive drugs should never be used in cases of PLE secondary to infections.

Case reports have described success in patients with PLE secondary to primary intestinal lymphangiectasia (Waldmann disease) using everolimus^[50] and rapamycin in a child with tuberous sclerosis complex.^[51]

Surgical Care

Conner et al reported a case in which localized resection of the involved bowel successfully treated the condition.^[52]

In patients who have undergone a Fontan procedure, fenestration of the baffle that separates the systemic venous pathway from the pulmonary venous atrium has been performed to treat PLE, and in some cases the symptoms have resolved, presumably because of the decrease in systemic venous pressure.

Cardiac transplantation has also been performed for the management of intractable PLE related to previous Fontan surgery, with complete resolution of symptoms in most cases and with survival comparable to patients with other indications for undergoing transplantation.^[53]

In another case series of 3 patients who presented with PLE after undergoing the Fontan procedure and 2 patients after undergoing thoracic duct ligation, abnormal lymphatics visualized on lymphatic imaging were percutaneously accessed and embolized with lipiodol or n-BCA glue. This resulted in improvement in albumin level and symptoms.^[47]

Pericardiectomy resulted in significant improvement of severe hypoalbuminemia in patients with constrictive pericarditis-associated PLE.^[54]

Diet

In patients whose PLE is related to lymphatic pathology, decreasing the lymphatic circulation provides some benefit. This requires dietary limitation of long-chain triglycerides because their absorption from the gut stimulates lymphatic flow. In order to provide adequate energy, medium-chain triglycerides must be added as an alternative source of lipid calories.

As described below, fat soluble vitamins must also be supplemented because their absorption is compromised in these patients.

Long-Term Monitoring

Serial measurements of albumin, immunogloblins, lymphocytes, cholesterol, and fat soluble vitamins should be incorporated into the management of any patients with previous history or risk factors for PLE.

Medication

Cakir M, Ersoz S, Akbulut UE. Disseminated cytomegalovirus infection and protein losing enteropathy as presenting feature of pediatric patient with Crohn's disease. Pediatr Gastroenterol Hepatol Nutr. 2015 Mar. 18 (1):60-5. [Medline].
Magdo HS, Stillwell TL, Greenhawt MJ, Stringer KA, Yu S, Fifer CG, et al. Immune Abnormalities in Fontan Protein-Losing Enteropathy: A Case-Control Study. J Pediatr. 2015 Aug. 167 (2):331-7. [Medline].
Schumacher KR, Stringer KA, Donohue JE, Yu S, Shaver A, Caruthers RL, et al. Fontan-associated protein-losing enteropathy and plastic bronchitis. J Pediatr. 2015 Apr. 166 (4):970-7. [Medline].
Elkadri A, Thoeni C, Deharvengt SJ, Murchie R, Guo C, Stavropoulos JD, et al. Mutations in Plasmalemma Vesicle Associated Protein Result in Sieving Protein-Losing Enteropathy Characterized by Hypoproteinemia, Hypoalbuminemia, and Hypertriglyceridemia. Cell Mol Gastroenterol Hepatol. 2015 Jul. 1 (4):381-394.e7. [Medline].
Damen G, de Klerk H, Huijmans J, den Hollander J, Sinaasappel M. Gastrointestinal and other clinical manifestations in 17 children with congenital disorders of glycosylation type Ia, Ib, and Ic. J Pediatr Gastroenterol Nutr. 2004 Mar. 38(3):282-7. [Medline].
Bode L, Freeze HH. Applied glycoproteomics--approaches to study genetic-environmental collisions causing protein-losing enteropathy. Biochim Biophys Acta. 2006 Apr. 1760(4):547-59. [Medline].
Warnes CA, Williams RG, Bashore TM, Child JS, Connolly HM, Dearani JA, et al. ACC/AHA 2008 Guidelines for the Management of Adults with Congenital Heart Disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing committee to develop guidelines on the management of adults with congenital heart disease). Circulation. 2008 Dec 2. 118 (23):e714-833. [Medline].
Meadows J, Jenkins K. Protein-losing enteropathy: integrating a new disease paradigm into recommendations for prevention and treatment. Cardiol Young. 2011 Aug. 21(4):363-77. [Medline].
Ohuchi H, Yasuda K, Miyazaki A, Kitano M, Sakaguchi H, Yazaki S, et al. Haemodynamic characteristics before and after the onset of protein losing enteropathy in patients after the Fontan operation. Eur J Cardiothorac Surg. 2013 Mar. 43(3):e49-57. [Medline].
Yu JJ, Yun TJ, Yun SC, Im YM, Lee SC, Shin HJ, et al. Low pulmonary vascular compliance predisposes post-Fontan patients to protein-losing enteropathy. Int J Cardiol. 2011 Sep 22. [Medline].
Kim GB, Kwon BS, Bae EJ, Noh CI, Choi JY. Significance of circulating hepatocyte growth factor in protein-losing enteropathy after Fontan operation. Pediatr Cardiol. 2011 Oct. 32(7):917-23. [Medline].
Mertens L, Hagler DJ, Sauer U, Somerville J, Gewillig M. Protein-losing enteropathy after the Fontan operation: an international multicenter study. PLE study group. J Thorac Cardiovasc Surg. 1998 May. 115(5):1063-73. [Medline].
Ono M, Kasnar-Samprec J, Hager A, Cleuziou J, Burri M, Langenbach C, et al. Clinical outcome following total cavopulmonary connection: a 20-year single-centre experience. Eur J Cardiothorac Surg. 2016 Mar 23. [Medline].
Patel JK, Loomes KM, Goldberg DJ, Mercer-Rosa L, Dodds K, Rychik J. Early Impact of Fontan Operation on Enteric Protein Loss. Ann Thorac Surg. 2016 Mar. 101 (3):1025-30. [Medline].
Magdo HS, Stillwell TL, Greenhawt MJ, Stringer KA, Yu S, Fifer CG, et al. Immune Abnormalities in Fontan Protein-Losing Enteropathy: A Case-Control Study. J Pediatr. 2015 Aug. 167 (2):331-7. [Medline].
Schumacher KR, Gossett J, Guleserian K, Naftel DC, Pruitt E, Dodd D, et al. Fontan-associated protein-losing enteropathy and heart transplant: A Pediatric Heart Transplant Study analysis. J Heart Lung Transplant. 2015 Sep. 34 (9):1169-76. [Medline].
John AS, Johnson JA, Khan M, Driscoll DJ, Warnes CA, Cetta F. Clinical outcomes and improved survival in patients with protein-losing enteropathy after the Fontan operation. J Am Coll Cardiol. 2014 Jul 8. 64 (1):54-62. [Medline].
Mahjoub F, Sani MN, Tabari AK, Monajemzadeh M, Zandieh S. An unusual cause of protein losing enteropathy in a 2.5-year-old girl: meso-intestinal fibrosis. European J Pediatr Surg Rep. 2014 Jun. 2 (1):29-31. [Medline]. [Full Text].
Weng MT, Wong JM, Shin SR, Yao M, Wei SC. Papillary thyroid cancer associated with light-chain amyloidosis initially presenting with small-bowel bleeding and protein-losing enteropathy. J Clin Oncol. 2010 Oct 10. 28(29):e557-9. [Medline].
Hwang YY, Leung AY, Ng IO, Chan GS, Chan KW, Tse E, et al. Protein-losing enteropathy due to T-cell large granular lymphocyte leukemia. J Clin Oncol. 2009 Apr 20. 27(12):2097-8. [Medline].
Burrow TA, Cohen MB, Bokulic R, et al. Gaucher disease: progressive mesenteric and mediastinal lymphadenopathy despite enzyme therapy. J Pediatr. 2007 Feb. 150(2):202-6. [Medline].
Damry N, Hottat N, Azzi N, Ferster A, Avni F. Unusual findings in two cases of Langerhans' cell histiocytosis. Pediatr Radiol. 2000 Mar. 30(3):196-9. [Medline].
Alreheili K, AlMehaidib A, Alsaleem K, Banemi M, Aldekhail W, Al-Mayouf SM. Intestinal lymphangiectasia in a patient with infantile systemic hyalinosis syndrome: a rare cause of protein-losing enteropathy. Ann Saudi Med. 2012 Mar-Apr. 32(2):206-8. [Medline].
Gökçe I, Gökçe S, Kiliç A, Bozlar U, Kocaoglu M, Ongürü O. Familial Mediteranean fever with protein-losing enteropathy due to constrictive pericarditis. World J Pediatr. 2011 Nov. 7(4):365-7. [Medline].
Peters B, Schuurs-Hoeijmakers JH, Fuijkschot J, Reimer A, van der Flier M, Lugtenberg D, et al. Protein-losing enteropathy in camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome. Pediatr Rheumatol Online J. 2016 May 25. 14 (1):32. [Medline].
Yamashita K, Saito M, Itoh M, et al. Juvenile polyposis complicated with protein losing gastropathy. Intern Med. 2009. 48(5):335-8. [Medline].
Kok J, Chen SC, Anderson L, et al. Protein-losing enteropathy and hypogammaglobulinaemia as first manifestations of disseminated histoplasmosis coincident with Nocardia infection. J Med Microbiol. 2010 May. 59:610-3. [Medline].
Ogawa E, Murata M, Unno M, et al. Protein-losing enteropathy during highly active antiretroviral therapy in a patient with AIDS-related disseminated Mycobacterial avium complex infection. J Infect Chemother. 2009 Aug. 15(4):252-6. [Medline].
Berni AD, Elias Júnior E, Arão Filho A, Paniago AM. Protein-losing enteropathy in paracoccidioidomycosis identified by scintigraphy: report of three cases. Braz J Infect Dis. 2010 Sep-Oct. 14(5):540-3. [Medline].
Yamamoto M, Nishibuchi I, Matsuyama A, et al. Gastric carcinoma with protein-losing gastroenteropathy: report of a case. Surg Today. 2011 Jan. 41(1):125-9. [Medline].
Nishino A, Hanaoka M, Katsumata Y, Kawaguchi Y, Yamanaka H. Technetium-99m Albumin Scintigraphy in Protein-Losing Gastroenteropathy With Systemic Lupus Erythematosus: Typical Diagnostic Pattern of Radiotracer Leakage and Chronological Improvement by Treatment. J Clin Rheumatol. 2017 Jan. 23 (1):41-42. [Medline].
Salstrom JL, Kent M, Liang X, Wang M. Toddlers with anasarca and severe anemia: a lesson in preventive medicine. Curr Opin Pediatr. 2012 Feb. 24(1):129-33. [Medline].
Hourigan SK, Anders RA, Mitchell SE, Schwarz KB, Lau H, Karnsakul W. Chronic diarrhea, ascites, and protein-losing enteropathy in an infant with hepatic venous outflow obstruction after liver transplantation. Pediatr Transplant. 2012 Nov. 16(7):E328-31. [Medline].
Camarero Salces C, Enes Romero P, Redondo C, Rizo Pascual JM, Roy Ariño G. Collagenous colitis and collagenous gastritis in a 9 year old girl: a case report and review of the literature. Acta Gastroenterol Belg. 2011 Sep. 74(3):468-74. [Medline].
Morava E, Tiemes V, Thiel C, et al. ALG6-CDG: a recognizable phenotype with epilepsy, proximal muscle weakness, ataxia and behavioral and limb anomalies. J Inherit Metab Dis. 2016 Jun 10. [Medline].
Yang C, Dehner LP. Protein-losing enteropathy with intestinal lymphangiectasia in skeletal dysplasia with Lys650Met mutation. Am J Med Genet A. 2016 May 23. [Medline].
Stephen J, Vilboux T, Haberman Y, Pri-Chen H, Pode-Shakked B, Mazaheri S, et al. Congenital protein losing enteropathy: an inborn error of lipid metabolism due to DGAT1 mutations. Eur J Hum Genet. 2016 Feb 17. [Medline].
McMillan T. Neonatal diabetes and protein losing enteropathy: a case report. BMC Medical genetics.
Jackson CC, Best L, Lorenzo L, Casanova JL, Wacker J, Bertz S, et al. A Multiplex Kindred with Hennekam Syndrome due to Homozygosity for a CCBE1 Mutation that does not Prevent Protein Expression. J Clin Immunol. 2016 Jan. 36 (1):19-27. [Medline].
Frosk P, Chodirker B, Simard L, El-Matary W, Hanlon-Dearman A, Schwartzentruber J, et al. A novel CCBE1 mutation leading to a mild form of hennekam syndrome: case report and review of the literature. BMC Med Genet. 2015 Apr 30. 16:28. [Medline].
Berges-Raso I, Capel I, Caixàs A, Trallero R, Rigla M. Hypothyroidism and protein-losing enteropathy: A case report. Endocrinol Nutr. 2016 Feb. 63 (2):95-6. [Medline].
Higuchi R, Booka M, Suzuki H, Tsuno H. Protein-losing enteropathy and erythema caused by egg allergy in a breast-fed infant. Pediatr Int. 2016 May. 58 (5):422-424. [Medline].
Liu NF, Lu Q, Wang CG, Zhou JG. Magnetic resonance imaging as a new method to diagnose protein losing enteropathy. Lymphology. 2008 Sep. 41(3):111-5. [Medline].
Kinsell L, Margen S, Tarver H. J Clin Invest. 1950. 29:238.
Gordon RS. J Polym Sci. 1957. 31:191.
Martinez-Sanchis B, Cortés-Vizcaíno V, Frontado-Morales L, Sopena-Novales P. Intestinal uptake of (99m)Tc-MDP: a case report of protein-losing enteropathy correlated with pathology findings from autopsy. Ann Nucl Med. 2011 Feb. 25(2):139-41. [Medline].
Itkin M. Protein-losing enteropathy: redefining the anatomy and pathophysiology and providing novel therapy. Journal of Vascular and Interventional Radiology. 2017. 28:S135-S136.
Liu M, Liu L, Zhou HM. [Reversal of protein-losing enteropathy with heparin therapy in a patient after Fontan operation]. Zhonghua Er Ke Za Zhi. 2009 Jan. 47(1):76-7. [Medline].
Schumacher KR, Cools M, Goldstein BH, Ioffe-Dahan V, King K, Gaffney D, et al. Oral budesonide treatment for protein-losing enteropathy in Fontan-palliated patients. Pediatr Cardiol. 2011 Oct. 32(7):966-71. [Medline].
Ozeki M, Hori T, Kanda K, Kawamoto N, Ibuka T, Miyazaki T, et al. Everolimus for Primary Intestinal Lymphangiectasia With Protein-Losing Enteropathy. Pediatrics. 2016 Mar. 137 (3):e20152562. [Medline].
Pollack SF, Geffrey AL, Thiele EA, Shah U. Primary intestinal lymphangiectasia treated with rapamycin in a child with tuberous sclerosis complex (TSC). Am J Med Genet A. 2015 Sep. 167A (9):2209-12. [Medline].
Bac DJ, Van Hagen PM, Postema PT, et al. Octreotide for protein-losing enteropathy with intestinal lymphangiectasia. Lancet. 1995 Jun 24. 345(8965):1639. [Medline].
Bai JC, Sambuelli A, Niveloni S, et al. Alpha 1-antitrypsin clearance as an aid in the management of patients with celiac disease. Am J Gastroenterol. 1991 Aug. 86(8):986-91. [Medline].
Moriyama H, Kohno T, Nishiyama T, Hattori O, Maekawa Y, Yoshida K, et al. Constrictive Pericarditis and Protein-Losing Enteropathy: Is Extremely Severe Hypoalbuminemia Reversible by Pericardiectomy?. Circ Heart Fail. 2016 Dec. 9 (12):[Medline].

Media Gallery

of 0

Author

Simon S Rabinowitz, MD, PhD, FAAP Professor of Clinical Pediatrics, Vice Chairman, Clinical Practice Development, Pediatric Gastroenterology, Hepatology, and Nutrition, State University of New York Downstate College of Medicine, The Children's Hospital at Downstate

Simon S Rabinowitz, MD, PhD, FAAP is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American College of Gastroenterology, American Gastroenterological Association, American Medical Association, New York Academy of Sciences, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, Phi Beta Kappa, Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

Coauthor(s)

Nonyelum Erica Ebigbo, MBBS Resident Physician, Department of Pediatrics, Richmond University Medical Center

Nonyelum Erica Ebigbo, MBBS is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

David A Piccoli, MD Chief of Pediatric Gastroenterology, Hepatology and Nutrition, The Children's Hospital of Philadelphia; Professor, University of Pennsylvania School of Medicine

David A Piccoli, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition

Disclosure: Nothing to disclose.

Chief Editor

Carmen Cuffari, MD Associate Professor, Department of Pediatrics, Division of Gastroenterology/Nutrition, Johns Hopkins University School of Medicine

Carmen Cuffari, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, Royal College of Physicians and Surgeons of Canada

Disclosure: Received honoraria from Prometheus Laboratories for speaking and teaching; Received honoraria from Abbott Nutritionals for speaking and teaching. for: Abbott Nutritional, Abbvie, speakers' bureau.

Additional Contributors

Robert Baldassano, MD Director, Center for Pediatric Inflammatory Bowel Disease, Children's Hospital of Philadelphia; Professor, Department of Pediatrics, Division of Gastroenterology and Nutrition, University of Pennsylvania School of Medicine

Robert Baldassano, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition

Disclosure: Received consulting fee from Abbott, Inc for consulting.

Brianna Devito University at Buffalo, The State University of New York

Disclosure: Nothing to disclose.

Jessica A Epstein State University of New York Downstate College of Medicine

Jessica A Epstein is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Psychiatric Association

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author Barry K Wershil, MD, to the original writing and development of this article.

Sections Pediatric Protein-Losing Enteropathy
Overview
Presentation
DDx
Workup
Treatment
Medication
Follow-up
References

Pediatric Protein-Losing Enteropathy Treatment & Management

Medical Care

Surgical Care

Diet

Long-Term Monitoring

About

Membership

Apps

WebMD Network

Editions

Pediatric Protein-Losing Enteropathy Treatment & Management

Medical Care

Surgical Care

Diet

Long-Term Monitoring

References

Tables

Contributor Information and Disclosures

What would you like to print?

Find Us On

About

Membership

Apps

WebMD Network

Editions