Makindo Medical Notes

Long-term complications of Protein Losing Enteropathy (PLE) include severe malnutrition, recurrent infections due to immunoglobulin loss, thromboembolic events resulting from hypoproteinemia, and progressive organ dysfunction—particularly in cases where cardiac or lymphatic causes are involved.

About

• Protein Losing Enteropathy (PLE): A condition characterized by excessive loss of serum proteins, including albumin, across the gastrointestinal mucosa.
• Protein loss exceeds synthesis: The rate of protein loss surpasses the body’s ability to synthesize new proteins, leading to hypoproteinemia.

Aetiology (Mechanisms of PLE)

• Lymphatic obstruction: Conditions affecting the lymphatic system can lead to impaired lymphatic drainage, causing protein leakage into the gastrointestinal tract.
• Abnormal mucosal integrity: Damage to the intestinal mucosa, often due to inflammation or ulceration, allows proteins to escape from the bloodstream into the GI tract.
• Localized ulceration: Ulcers or erosions in the GI mucosa, common in inflammatory or infectious conditions, can also lead to significant protein loss.

Causes of Protein Losing Enteropathy

• Inflammatory Bowel Disease (IBD): Crohn’s disease and ulcerative colitis can both result in significant protein loss through inflamed or ulcerated bowel walls.
• Menetrier's disease: A rare condition affecting the gastric mucosa, leading to large folds in the stomach and significant protein loss.
• Coeliac disease: Malabsorption caused by gluten sensitivity can lead to damage of the small intestine and subsequent protein loss.
• Intestinal lymphangiectasia: A condition where dilated lymphatic vessels in the intestine lead to protein leakage into the gut.
• Amyloidosis: Deposition of amyloid protein in the gastrointestinal tract can lead to protein loss through the mucosa.
• Pseudomembranous colitis: Inflammation of the colon, often due to Clostridium difficile infection, can lead to protein loss.
• Tuberculosis and Sarcoidosis: Both granulomatous diseases can affect the GI tract, leading to protein loss through inflammation and ulceration.
• Whipple’s disease: A rare bacterial infection affecting the GI tract, resulting in protein loss.
• AIDS: Advanced HIV infection can damage the immune system and gastrointestinal mucosa, leading to protein loss.

Clinical Features

• Anasarca: Generalized edema due to low serum albumin levels, resulting in fluid accumulation in tissues.
• Weight loss and diarrhoea: Progressive weight loss and chronic diarrhoea are common symptoms.
• Cachexia: Severe malnutrition in advanced cases, leading to muscle wasting and general weakness.
• Fat-soluble vitamin deficiencies: Due to malabsorption, patients may develop deficiencies in vitamins A, D, E, and K.
• Recurrent infections: Hypogammaglobulinemia, resulting from the loss of immunoglobulins in the gut, predisposes patients to recurrent infections.

Investigations

• Serum Albumin and Total Protein: Typically low, reflecting the protein loss through the gastrointestinal tract.
• Faecal Alpha-1 Antitrypsin Clearance Test: Elevated levels indicate excessive protein loss via the gut. This test helps confirm the diagnosis of PLE.
• Serum Immunoglobulins: Hypogammaglobulinemia, particularly of IgG, may be observed, indicating immunoglobulin loss through the GI tract.
• Lymphocyte Count: Lymphopenia (low lymphocyte count) may be seen, particularly in cases of intestinal lymphangiectasia or lymphatic obstruction.
• CT or MRI of the Abdomen: Imaging studies can detect masses, intestinal lymphangiectasia, or retroperitoneal fibrosis, all of which can cause PLE.
• Echocardiography: Used to rule out constrictive pericarditis, which can cause PLE through impaired lymphatic drainage from the heart.
• Lymphangiography: This specialized imaging is useful in cases where lymphatic obstruction or malformation is suspected as the cause of protein loss.
• Upper Endoscopy and Colonoscopy with Biopsy: Essential for diagnosing underlying gastrointestinal diseases such as IBD, coeliac disease, or GI malignancies.
• Capsule Endoscopy: A valuable tool for visualizing the small intestine, which is difficult to access with conventional endoscopy.

Management

• Nutrition and protein supplementation: A high-protein diet is recommended, and in severe cases, albumin infusions may be necessary to correct hypoproteinemia.
• Vitamin and mineral replacement: Supplementation with fat-soluble vitamins (A, D, E, K) and minerals such as calcium and magnesium is often required. Total parenteral nutrition (TPN) may be necessary in cases where oral intake is inadequate.
• Coeliac disease: A strict gluten-free diet is essential for managing PLE associated with coeliac disease.
• Inflammatory Bowel Disease (IBD): Treatment may include immunosuppressants, biologic therapies, and anti-inflammatory agents to control disease activity and reduce protein loss.
• Intestinal lymphangiectasia: A low-fat diet supplemented with medium-chain triglycerides (MCTs) is recommended to reduce lymphatic pressure and protein loss. Octreotide, a somatostatin analog, may also help in reducing protein loss in some cases.
• Surgical intervention: In cases of localized lymphatic obstruction or GI tumours, surgery may be required to relieve the obstruction and reduce protein loss.
• Immunoglobulin replacement therapy: In cases of severe hypogammaglobulinemia with recurrent infections, immunoglobulin replacement may be necessary to boost the immune system.