Protein Losing Enteropathy

Description

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

• Disruption to the intestinal wall due to inflammation or infiltrative disease
• Congestion caused by portal hypertension, posterior caval syndrome or right-sided heart failure
• Gastro-intestinal haemorrhage

Hence, there are numerous causes of PLE in cats and dogs , including lymphangiectasia, infectious causes, structural causes, neoplasia, inflammation, endoparasites and gastrointestinal haemorrhage.

The major causes of PLE in adult dogs are inflammatory bowel disease (IBD), alimentary tract lymphoma, fungal infections (e.g. histoplasmosis). Other causes include ulcerations or erosions, severe disease of intestinal crypts and parasites. The most common causes in very young dogs are hookworms and chronic intussusception. Chronic intussusception results from acute enteritis which has not resolved completely. The animal shows some clinical improvement but diarrhoea still continues. PLE is less common in cats than dogs, and most often caused by alimentary tract lymphoma and IBD. Cats almost never suffer from lymphangiectasia, and rarely have severe parasitic infection severe enough to cause PLE. Non-intestinal diseases can be associated with PLE include ]congestive heart failure, caval obstruction and portal hypertension. However, these animals usually present with ascites rather than diarrhoea.

Signalment

The following breeds of dog may be afflicted:

• Basenji
• Lundehund
• Soft-Coated Wheaten Terrier
  • May have concurrent protein-losing nephropathy
  • Related to chronic granulomatous lymphangitis and enteritis
  • Most affected animals have a common ancestor
  • Females are more commonly affected that males
• Yorkshire Terrier
• Shar Pei

• 

  Basenji

  WikiCommons

• 

  Shar Pei

  WikiCommons

• 

  Soft Coated Wheaten Terrier

  WikiCommons

• 

  Yorkshire Terrier

  WikiCommons

Diagnosis

Clinical Signs

• Weight loss (predominant feature).
• Vomiting and diarrhoea ± melaena.
• Oedema, ascites and pleural effusion due to reduced plasma oncotic pressure.
• Thickened intestines related to the pathological process.
• Thromboembolic disease due to the loss of anticoagulants such as antithrombin III.
• Hypocalcaemic tetany due to a reduced ability to absorb vitamin D.

Laboratory Tests

Haematology

• Lymphopaenia

Biochemistry

• Panhypoproteinaemia
  • Hypoglobulinaemia with hypoalbuminaemia is a pattern more suggestive of PLE as albumin is lost in excess of globulin in protein-losing nephropathy.
• Hypocholesterolaemia
• Hypocalcaemia
  • Ionised calcium concentration should be measured to determine the significance of this finding as serum calcium concentration will fall as protein levels fall.

Other Tests

• Measurement of faecal alpha1-protease inhibitor

Diagnostic Imaging

Radiography

• Abdominal radiographs are usually unremarkable.
• Thoracic radiographs may show pleural effusion, metastatic neoplasia or eveidence of histoplasmosis).

Ultrasonography

• This may reveal thickening of intestines, mesenteric lymphadenopathy or abdominal effusion.

Histopathology

• Endoscopically-guided multiple biopsies are useful. Surgical biopsy may be required for a 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.
• Animals with PLE have a greater risk of biopsy site dehiscence with the subsequent development of peritonitis.

Treatment

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

Plasma transfusion

• This may be used to increase plasma volume. However, much of the albumin is lost in the gut and a substantial amount fails to remain in the intravascular compartment. Therefore, the extent of increase in serum albumin level is not great.
• Administration of colloid may be more suitable if it is essential to increase the plasma oncotic pressure.

Diuretics

• These can be used to reduce any ascites or pleural effusion.
• Spironolactone may be more effective than frusemide.

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.

From Pathology

Causes of PLE

• Severe inflammatory disease.
  • Protein is lost in exudate.
• Lymphangiectasia.
  • Loss of protein-rich lymph due to obstruction of gut lymphatics.
• Increased mucosal permeability.
  • E.g. erosions, loss of tight junctions, lymphosarcoma.
• Increased loss of enterocytes (less important).
• Also:
  • Immunoproliferative enteropathy
  • Lymphocytic plasmacytic enteritis
  • Eosinophilic enteritis
  • GI ulceration/erosion
  • Giardiasis
  • Chronic intussusception
  • Small intestinal bacterial overgrowth
  • Neoplasia
  • Hypoalbunimaemia causing mural oedema
  • Increased activation of tissue plasminogen activator
  • Systemic lupus erythematosis (SLE)
  • Vascular lesion in the GI mucosa
  • Chemotherapy/radiotherapy.

Pathology

• Lesions include:
  • Inflammatory bowel disease
  • Dilated lymphatics
  • Lipogranulomatous lymphangitis.
• Intestinal crypts become dilated with mucus, sloughed epithelial cells with or without inflammatory cells.
• PLE is also 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.

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.