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What

Protein losing enteropathy (PLE) is a disorder of the gastro-intestinal (GI) tract that involves excessive loss of important plasma proteins into the intestines. The body is not able to produce enough proteins to make up for the loss. This leads to severe bouts of diarrhea and clinical signs indicating low protein levels, such as swelling, malnutrition and immune system problems. PLE can result from any sort of process that causes damage to the lining of the GI tract.

Who

PLE can affect people of any age, race, or sex. How often protein losing enteropathy occurs in children is unknown. Some people with certain disease processes, which are mentioned below, are at increased risk of developing protein losing enteropathy.

Signs and Symptoms

Proteins are important components found in the body’s cells, tissues, blood and lymphatic systems. They keep plasma flowing in the blood and lymphatic vessels, so low protein levels cause all the plasma to leak out of the vessels and we see swelling in the child. Some other proteins called immunoglobulins are important components of the body’s immune system, which is used to fight off infection. Low immunoglobulin levels may lead to increased risk of infection. Signs and symptoms of PLE develop because of the body’s loss of proteins and immunoglobulins, which can be seen in • Edema - swelling of the legs and abdomen. Sometimes there is swelling of the face if the lymphatic system is obstructed. • Gastrointestinal complaints – diarrhea, abdominal pain • Weight loss • Symptoms of fat malabsorption and fat-soluble vitamin deficiency - vision changes and night blindness (vitamin A), rickets (vitamin D), anemia and neurological problems (vitamin E), and increased bruising (vitamin K). • Very rarely, increased susceptibility to infection • And in severe cases, the low protein level may cause fluid to leak around the heart and lungs, causing cardiac and respiratory emergencies

Possible Causes

Any process that leads to profound leakage of proteins in the GI tract can lead to protein-losing enteropathy. There are three main mechanisms that lead to protein-losing enteropathy, described here followed by examples of possible diseases that will lead to the protein leakage. 1. Lymphatic obstruction: The lymphatic system is helpful in the body’s defense against infection, filtering out organisms that cause disease as well as producing white blood cells and antibodies to fight infection. It consists of a network of tiny ducts that drain tissue fluid to lymph nodes and ultimately back to the bloodstream. Lymphatic fluid also contains proteins and fats. A large part of the lymphatic system is found in the walls of the intestines. Any obstruction of the lymphatics can produce increased pressure throughout the lymphatic system in the GI tract. This leads to loss of lymphatic fluid, which contains proteins and white blood cells, into the GI tract. Causes include: • Primary intestinal lymphangiectasia – Children are born with abnormal lymphatic drainage from the intestines, and subsequently protein leaks out into the GI tract. Children with Turner syndrome or Noonan syndrome seem at increased risk of developing primary intestinal lymphangiectasia. • Cardiac diseases like congestive heart failure or constrictive pericarditis - Children who received the Fontan surgery for heart malformations are also at risk of developing protein-losing enteropathy. • Inflammatory bowel disease • Lymphoenteric fistula • Lymphoma • Rarer causes like tuberculosis, sarcoidosis, and retroperitoneal fibrosis 2. Intestinal erosions or ulcerations: The walls of the GI tract are disrupted, leading to increased leakage of proteins. These patients often do not have low immunoglobulin or white blood cell levels because their lymphatic systems are intact. • Erosions or ulcerations of the esophagus, stomach, or intestines • Graft versus host disease, which is a GI complication following bone marrow transplant • Pseudomembranous colitis, which is a GI complication from infection by the bacteria C. dificile • Ulcerative colitis, which is an example of inflammatory bowel disease • Other rarer causes include carcinoid syndrome, neurofibromatosis, and protein dyscrasias 3. Intestinal permeability (leakiness) without erosions or ulcerations: The cells of the GI tract are damaged or lost, leading to increased leakage of protein into the intestines. • Tropical sprue • Celiac sprue • Eosinophilic gastroenteritis • Intestinal parasites • Small intestinal bacterial overgrowth • Henoch-Schonlein purpura • Other rarer causes like lymphocytic colitis, Menetrier’s disease, and lupus

Diagnosis

Your doctor will ask for a detailed diet history in your child when evaluating for possible protein losing enteropathy. There are numerous blood tests that help lead to the diagnosis of PLE. Children may have low levels of two important types of blood proteins: albumin and immunoglobulins. The white blood cell count may also be low if there is lymphatic obstruction. Your doctor will also check the stool for alpha 1 anti-trypsin, a protein that is not normally found in the stool. A radiological study using radionuclide-labeled serum albumin can be given intravenously and doctors can check the stool to see if the labeled albumin was excreted. If your doctors are looking for a specific cause to the protein-losing enteropathy, they may want further studies. CT (computed tomography) studies and lymphangiograms may be ordered to look for signs of lymphatic obstruction. Chest X-rays and echocardiograms will help diagnose heart disease. Endoscopies and mucosal biopsies will help diagnose erosive or ulcerative GI conditions.

Treatment

Treatment involves taking care of the primary disease process that is leading to the PLE. Patients with intestinal parasites need antibiotics. Patients with congestive heart failure will need medications to relieve the heart disease. Corticosteroids and a blood thinner called heparin have been used to treat children who had a Fontan procedure and developed PLE. Surgery to relieve the lymphatic obstruction may be indicated. Diet modification is also important. A low-fat, high protein diet supplemented with a particular class of fats called medium chain triglycerides may help in those patients with lymphatic obstruction who are experiencing fat malabsorption. This diet will be designed by a nutritionist. Supplementation with the fat-soluble vitamins A, D, E, and K will help with growth and development. Those with celiac sprue will benefit from a gluten-free diet. Other supportive therapy includes support stockings or diuretics to reduce the swelling in the legs. Careful, regular, inspection of the skin and attention to preventing areas of pressure is needed to prevent infection and skin breakdown. Exercise to reduce development of blood clots is encouraged.

Prognosis

The goal of therapy is to identify the cause and develop appropriate dietary, medical, and, if necessary, surgical interventions to control the primary process leading to PLE. While prognosis depends upon the underlying disease, more than half of patients with PLE will eventually reach partial or complete remission. These patients are able to continue on with their lives but will need to be closely followed by their doctors to maintain an optimal nutritional status and normal blood protein levels.

Connect with other parents

In the spirit of community and support, Madisons Foundation offers the unique service of connecting parents of children with rare diseases. If you would like to be connected to other parents of children with this disease, please fill out this brief form.

Weblinks

Yahoo! Health Encyclopedia
Brief description of protein-losing enteropathy with illustration.

Emedicine
Detailed website using medical terminology explaining the causes, diagnosis, and treatment of PLE.

Protein Losing Enteropathy After the Fontan Operation
Information from the congenital Heart Network for parents of children born with cardiac disease who had the Fontan operation and subsequently developed protein losing enteropathy.

Google Search for Protein Losing Enteropathy (PLE)

References and Sources

Wershil, BK & Garcia A (2002). Pediatric Protein Losing Enteropathy. www.emedicine.com/ped/topic1909.htm Kim K (2002). Protein-Losing Gastroenteropathy. In Feldman: Sleisenger & Fordtran (eds) Gastrointestinal and Liver Disease, 7th ed. Elsevier, p 446-452. Wright R (2003). Protein Losing Enteropathy. http://www.emedicine.com/med/topic1926.htm Garcia-Careaga M & Kerner JA (2004). Malabsorptive Disorders. In: Behrman RE, Kliegman RM, Jenson HB (eds) Nelson Textbook of Pediatrics. 17th ed. WB Saunders, p1266.