Protein Losing Enteropathy (PLE)
(December 2003)
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Protein Losing Enteropathy.pdf)
Protein losing enteropathy (PLE) is a condition where increased protein loss through the bowel lining causes reduced serum protein levels. This syndrome can be the result of many disease states. Diagnosis of PLE should be considered in patients in whom hypoproteinaemia is present and when other causes have been excluded (see "Suggested Algorithm" below for other causes of protein loss).
Increased intestinal loss of protein occurs via one of two mechanisms:
- Mucosal dysfunction (injury or inflammation)
- Lymphatic dysfunction:
- granulomatous/neoplastic involvement
- congestive heart failure
- constrictive pericarditis
The anatomical site of protein loss varies, dependent on the underlying pathology, but can be anywhere from the stomach to the colon.
Causes of Protein Losing Enteropathy (PLE)
| Inflammatory exudation from mucosal erosion / ulceration | Mucosal disease without erosion or ulceration | Lymphatic Obstruction |
|---|
| Inflammatory bowel disease |
Coeliac disease |
Intestinal lymphangectasia, inc. yellow-nail syndrome |
Gastrointestinal malignancy: - Gastric carcinoma
- Lymphoma
- Kapos's sarcoma
- Alpha chain disease/IPSID
|
Infections: - Bacterial overgrowth
- Acute viral infection
- Parasitic
- Tropical sprue
- Whipple's disease
|
Right sided heart failure: - Congestive Heart Failure
- Constrictive pericarditis
- Congenital heart disease
|
| Behcet's disease |
Hypertrophic gastropathy |
Cirrhosis |
| Carcinoid syndrome |
Secretory hypertrophic gastropathy |
Hepatic or mesenteric venous obstruction |
| AriaNeurofibromatosis |
Rheumatic diseases: - Systemic Lupus Erythematosus
- Rheumatoid Arthritis
- Mixed Connective Tissue Disease
|
Enteric-lymphatic fistula |
| Waldenstrom's macroglobulinaemia |
Allergic gastroenteropathy |
Mesenteric Tuberculosis or sarcoidosis |
| Pseudomembraneous colitis |
Eosinophilic gastroenteritis |
Intestinal lymphoma |
| Amyloidosis (can have both urine & gastrointestinal protein loss) |
Vitamin B12 deficiency |
Chronic pancreatitis with pseudocysts |
| Erosive gastritis |
Henoch-Schonlein purpura |
Crohn's disease |
| NSAID enteropathy |
Lymphocytic colitis |
Systemic Lupus Erythematosus |
| Graft versus host disease |
Collagenous colitis |
Intestinal Endometriosis |
| Post chemotherapy |
|
Whipple's disease |
Laboratory Findings
The serum concentration of total protein will fall when the net gastrointestinal (GI) loss of protein is greater than the hepatic synthesis. Patients with PLE have normal or slightly increased hepatic protein synthesis, reflected by a normal or slightly increased prealbumin* level. Serum levels of individual proteins that normally have a rapid turnover (insulin, IgE, prealbumin) will be affected less with PLE states than those which have a slow turnover (albumin, IgM, IgA, IgG).
Pathological findings will also include those of the underlying disease.
Hypoalbuminaemia without:
- Proteinuria
- Reduced protein synthesis (prealbumin and prothrombin time)
- Reduced nutritional markers (ferritin, red cell folate, B12, zinc, calcium)
(Though these may be present, if secondary to the underlying disease process)
Low levels of:
- Gamma globulins
- Cholesterol
- Alpha 1 antitrypsin
- Fibrinogen
- Caeruloplasmin
Lymphopaenia - if marked can impair cellular mediated immunity.
Malabsorption of fat and fat-soluble vitamins.
Diagnosis / Investigations
Faecal alpha-1 antitrypsin levels are no longer performed by HAPS. The assay had limited accuracy and was falsely positive in patients with diarrhoea or GI blood loss.
Alternative Investigations to Consider
- Faecal Fat - globule size & quantitative faecal fat estimation
- Radiographic studies of the GI tract
- Endoscopy (upper, lower) and biopsy - consider asking for stains for Whipple's disease
- Consider CT / lymphangiography or lymphoscintigraphy
Prealbumin
Prealbumin (or transthyretin) is a serum transport protein for thyroxine and retinol-binding protein, and is not a precursor molecule of albumin. The prefix "pre-" refers to the position on serum protein electrophoresis, as it migrates in front of albumin. It has a half-life of 2-3 days, as compared to albumin, which has a half-life of 18-20 days. Levels of prealbumin can be lowered slightly during an acute phase (inflammatory) response. Prealbumin is involved in some types of amyloid disease.
Quantification of prealbumin requires a serum sample, approximately 0.5mL. Plasma is not suitable for quantification of this analyte
Suggested Algorithm for Investigation of Suspected PLE
About the Authors
Dr Theo de Malmanche, an Immunopathology Registrar, is the primary author of this HAPS Communique. HAPS Immunology would like to acknowledge Dr Ann Duggan, Gastroenterology Hunter Health, for her contribution. If you have any questions regarding this topic the Immunology staff would be happy to assist you on Telephone: (02) 49214000, Facsimile: (02) 49214400.
Immunology Clinical Contacts
Dr Theo de Malmanche - Registrar - 49214000
Professor Robert Clancy - 49236135
Dr Glenn Reeves - 49214000
Immunology Laboratory - 49214018