Protein Losing Enteropathy

Description

Protein-losing enteropathy (PLE) refers to the loss of plasma proteins into the gastro-intestinal (GI) tract, exceeding the absorptive capacity of the intestines. PLE can be caused by:

• Disruption to the intestinal wall due to inflammation or infiltrative disease
• Venous congestion of the GI tract
• GI haemorrhage

Hence, there are numerous causes of PLE in cats and dogs, including:

• Inflammation
  • Inflammatory Bowel Disease (including lymphocytic-plasmacytic enteritis, eosinophilic enteritis, granulomatous enteritis and histiocytic-ulcerative colitis)
  • Infectious disease
    • Giardia duodenalis
    • Hookworm
    • Histoplasmosis
  • Chronic intussusception in juvenile animals
• Lymphangiectasia
• Infiltrative disease
  • Alimentary lymphoma
• Venous congestion
  • Portal hypertension
  • Posterior caval syndrome
  • Right-sided congestive heart failure
• GI haemorrhage
  • This may occur with hypoadrenocorticism or with other causes of GI ulceration

Inflammatory bowel disease and lymphoma are the most common causes of PLE in both cats and dogs but lymphangiectasia occurs much more commonly in dogs than in cats. Chronic intussuscepta (usually occurring secondary to acute enteritis) and endoparasite infection are the most common causes of PLE in juvenile cats and dogs.

Rare causes of PLE include:

• Small intestinal bacterial overgrowth (SIBO)
• Hypoalbunimaemia causing intestinal mural oedema
• Increased activation of tissue plasminogen activator
• Systemic lupus erythematosis (SLE)
• Chemotherapy or radiotherapy

Signalment

The following breeds of dog show a predisposition for PLE:

• Basenji, related to secretory enteropathy
• Lundehund
• Soft-Coated Wheaten Terriers, which may have concurrent protein-losing nephropathy. Most affected animals of this breed have a common ancestor (thought to have lived in the USA) and females are more commonly affected than males
• Yorkshire Terrier
• Shar Pei

• 

  Basenji

  WikiCommons

• 

  Shar Pei

  WikiCommons

• 

  Soft Coated Wheaten Terrier

  WikiCommons

• 

  Yorkshire Terrier

  WikiCommons

Diagnosis

Clinical Signs

• Weight loss is the most evident sign.
• Diarrhoea occurs due to the loss of protein into the GI tract and subsequent osmotic movement of fluid. Melaena may occur with GI haemorrhage.
• Oedema, ascites and pleural effusion due to reduced plasma oncotic pressure.
• Thickened intestines may be detectable on abdominal palpation and this finding may be related to the primary pathological process.
• Thromboembolic disease due to the loss of plasma anticoagulants such as antithrombin III.
• Hypocalcaemic tetany due to a reduced ability to absorb the fat soluble vitamin D.

Laboratory Tests

Haematology

• Lymphopaenia occurs with lymphangiectasia due to the loss of lymph.

Biochemistry

• Panhypoproteinaemia
  • Hypoglobulinaemia with hypoalbuminaemia is a pattern more suggestive of PLE.
  • Albumin is usually lost in excess of globulin in protein losing nephropathy.
• Hypocholesterolaemia, especially in lymphangiectasia.
• Hypocalcaemia
  • Ionised calcium concentration should be measured to determine the significance of this finding as serum calcium concentration is closely related to total protein level.

Other Tests

• Measurement of faecal alpha1-protease inhibitor
  • This marker has a similar molecular weight to albumin and it is lost into the GI tract in PLE. Its concentration can therefore be measured in faeces as it is not degraded by GI enzymes. Faecal samples must be frozen on collection before submission to a laboratory in the USA.

• Administration of 51-Chromium labelled albumin
  • A radioactive marker (51-Chromium) is attached to recombinant albumin molecules before injection into animal. Faecal samples are collected to determine whether the labelled albumin is being lost into the GI tract. Although this test represents the 'gold standard' test, it is available only at a limited number of referral institutes.

Diagnostic Imaging

Radiography

The results of abdominal radiographs are usually unremarkable but discrete mass lesions or ascites may be evident. Thoracic radiographs may show the presence of pleural effusion, metastatic neoplasia or evidence of histoplasmosis).

Ultrasonography

• This may reveal:
  • Changes to intestinal wall structure, including:
    • Thickening without loss of normal layers (as with inflammatory bowel disease)
    • Thickening with loss of layers (as with infiltrative intestinal neoplasia)
    • 'Tiger stripes', an unreliable indicator of lymphangiectasia
  • Ascites or pleural effusion
  • Mesenteric lymphadenopathy

Histopathology

Endoscopy can be used to visualise the proximal intestinal luminal surface and to obtain grab biopsies. Surgical biopsies may be obtained for definitive diagnosis of lymphoma and secondary lymphangiectasia. A small fatty meal could be given the night before biopsy to increase the chance of diagnosing lymphangiectasia. Care should be taken with this procedure as animals with PLE have a greater risk of surgical wound dehiscence with the subsequent development of peritonitis.

Lesions that may be observed on histopathological analysis of biopsy samples include:

• • Signs of inflammatory bowel disease
  • Dilated lymphatics
  • Lipogranulomatous lymphangitis, especially in Soft-coated Wheaten terriers

• PLE may also be associated with protein losing nephropathy (PLN).
  • PLN may be a chronic sequelae to the PLE.
  • Follows immune complex deposition in the glomerulus, causing glomerulonephritis or glomerulosclerosis.
  • PLN causes hypoalbunaemian and hypercholesterolaemia.
  • Similar PLN and PLE lesions seen in young Besenjis with immunoproliferative enteropathy and glomerulosclerosis.

Treatment

Treatment of the underlying cause of disease should be initiated, if possible.

Plasma transfusion

This may be used to increase plasma volume but, as much of the albumin is lost into the gut, there may be a disappointing increase in serum albumin concentration after transfusion. Large colloids (such as hetastarch) may also be administered to try to maintain plasma oncotic pressure.

Diuretics

These may be used to reduce any ascites or pleural effusion and it has been suggested that spironolactone may be more effective than frusemide for this purpose.

Antithrombotic therapy

Treatment may be initiated with low dose aspirin to prevent the development of thrombo-embolism.

Dietary Supplementation with Calcium

Calcium carbonate may be added to the diet if a low serum concentration of ionised calcium is documented.

Prognosis

This depends on the underlying cause but Soft-coated Wheaten terriers are known to have a median survival time of five months after diagnosis of PLE and of two months if they suffer from concurrent protein-losing nephropathy.

References

• Ettinger, S.J. and Feldman, E. C. (2000) Textbook of Veterinary Internal Medicine Diseases of the Dog and Cat Volume 2 (Fifth Edition) W.B. Saunders Company.
• Hall, E.J, Simpson, J.W. and Williams, D.A. (2005) BSAVA Manual of Canine and Feline Gastroenterology (2nd Edition) BSAVA.
• Nelson, R.W. and Couto, C.G. (2009) Small Animal Internal Medicine (Fourth Edition) Mosby Elsevier.
• Willard, M. (2005) Protein-Losing Enteropathy in Dogs and Cats 30th World Congress of the WSAVA.