The protein-losing enteropathies (PLE) comprise a collection of intestinal, usually small intestinal, diseases typically associated with weight loss, hypoproteinemia caused by hypoalbuminemia or panhypoproteinemia, and variable signs of weight loss, vomiting and diarrhea. In dogs, PLE is most often a consequence of lymphocytic/plasmacytic enteritis (LPE) or other inflammatory infiltrative intestinal disease, intestinal lymphangiectasia (IL), or intestinal lymphoma; these diseases are the focus of this discussion. Because the presenting clinical findings and diagnostic features are similar for all three, they will be considered as a group with key differences pointed out where relevant. Readers should be aware that other diseases can contribute to the clinical manifestation of a PLE including hypoadrenocorticism, gastrointestinal ulcerative disease, other intestinal neoplasms, intestinal histoplasmosis and other chronic infections, gastrointestinal parasites, and chronic intestinal intussusception.

Etiological considerations

PLE can develop in animals of any age. Dog breeds that seem predisposed to the development of PLE include basenjis, Lundehunds, soft-coated wheaten terriers, Chinese Shar Peis, Rottweilers, German shepherds and Yorkshire terriers. Dogs are affected with PLE more often than cats despite the overlap in histological diagnoses of chronic intestinal diseases that exist between the species.

The clinical signs of PLE can be quite variable. Many dogs with PLE exhibit nonspecific signs, such as anorexia or lethargy and weight loss; some dogs may exhibit polyphagia. Diarrhea is one of the most consistent clinical signs referable to the GI tract, but is not seen in all patients with PLE. Those patients with diarrhea typically lack large bowel features such as mucus, fresh blood and tenesmus thus localizing to the small bowel. When diarrhea is not a presenting complaint, PLE should not necessarily be ruled out if otherwise compatible signs, such as weight loss, edema, or ascites, are present. Vomiting is also a frequent clinical sign in dogs with PLE. Dilation of intestinal lymphatics alone in dogs with IL does not seem to cause vomiting, but because many dogs with IL have intestinal inflammation, vomiting likely results from inflammatory stimuli.

Ascites, subcutaneous dependent edema, and pleural effusion are common in PLE patients. In most cases, fluid accumulates secondary to decreased colloid oncotic pressure from hypoproteinemia, particularly hypoalbuminemia. Effusions or edema may develop when serum albumin concentrations fall below 1.5 g/dl; effusions in these situations are usually pure transudates (low protein content, often less than 1 g/dl, and low nucleated cell counts). However, pure transudates in abdominal effusion can sometimes be seen in the context of serum albumin concentrations higher than 1.5 g/dl, suggesting that other pathophysiological factors that govern the formation of effusions, such as increased hydrostatic pressure or lymphatic obstruction, may contribute to fluid accumulation. It is important to remember that pure transudates in the abdomen can also be a consequence of portal hypertension. Chylothorax, and possibly chyloabdomen, can be seen in some patients with PLE secondary to IL.

In some dogs, clinical signs of thromboembolic disease, such as tachypnea and hyperpnea due to pulmonary thromboemboli, can develop; the author has also seen dogs with PLE die acutely from thromboembolic complications. The coagulation abnormalities that lead to thromboembolism in dogs with PLE are poorly characterized and understood but are attributed to imbalances between pro- and anti-coagulant factors, increased platelet aggregability or vascular endothelial injury, which have been documented in humans with inflammatory bowel diseases.

Diagnostic testing

Laboratory abnormalities in dogs with PLE can be quite variable. Anemia of chronic inflammation and neutrophilic leukocytosis secondary to stress or chronic inflammation may be observed in some dogs. Some dogs with IL have lymphopenia, but lymphopenia could also be a component of stress leukograms in such patients. Platelet counts may increase from chronic inflammation. Thrombocytopenia in a dog with PLE is unusual and suggests a complication of the disease, such as thromboembolism or disseminated intravascular coagulation.

Hypoalbuminemia is the most consistent laboratory abnormality in canine PLE. Some dogs, however, have normal albumin levels. Commonly, serum globulin concentration is also low. Globulins can be increased, or remain normal in the face of enteric protein loss, secondary to increased production associated with the inflammatory process. Total serum calcium level is often decreased as an artifact of low serum albumin concentration. Occasionally, the total corrected calcium concentration remains abnormally low, and some dogs will have persistently low ionized calcium concentrations.