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Diagnosing and managing cases of PLE

by
01 February 2014, at 12:00am

Jayne Laycock reports on her ‘pick of the month’ CPD webinar, Protein losing enteropathy due to lymphangiectasia in dogs, presented by Dr Jane Armstrong for The Webinar Vet

PROTEIN losing enteropathy (PLE) is a complex syndrome associated with the abnormal loss of protein through gastrointestinal mucosa where the loss of albumin cannot be compensated by the liver.

There are a number of underlying diseases which cause PLE including lymphangiectasia, inflammatory bowel disease (IBD) and gastrointestinal lymphoma. Diagnosis of PLE and its underlying causes can be challenging but Dr Armstrong managed to guide us with ease through the process of diagnosis, offering some great advice on how to manage these cases with as much success as possible.

PLE needs to be considered in any dog suffering from hypoalbuminaemia. Dr Armstrong noted that PLE is very uncommon in cats regardless of the type of bowel disease they develop. Often dogs with PLE will have a history of digestive problems such as weight loss, vomiting and/or diarrhoea.

Jane was keen to stress that not every case of PLE has overt gastrointestinal signs and should be considered in every hypoalbuminaemic dog, even without a history of obvious digestive problems. Profoundly hypoalbuminaemic dogs may have ascites and/or pleural effusion and these signs may be the sole complaint of the owner.

Other underlying causes of hypoalbuminaemia need to be ruled out including liver failure, protein losing nephropathy (PLN) and gastrointestinal haemorrhage. PLN can be ruled out by performing a urinalysis and, if protein is present, measuring the protein:creatinine ratio which should not be more than 0.5.

Also, dogs suffering from PLN will only be hypoalbuminaemic and not hypoglobulinaemic as globulin molecules are too large to pass through the glomerulus. Dogs suffering from PLE are more likely to be hypoproteinaemic, suffering from both hypoalbuminaemia and hypoglobulinaemia. Liver diseases that may cause hypoalbuminaemia, including portosystemic shunts, can usually be readily excluded if serum bile acids (pre- and post-prandial) are normal.

Other possible biochemical changes associated with cases of PLE include hypocholesterolaemia, lymphopaenia, low serum cobalamin and hypocalcaemia. Some cases of PLE may have a low ionised calcium secondary to poor absorption of vitamin D.

If severe enough, this can lead to muscle weakness, tremors and tetanic seizures. Rubbing and scratching of the face is another clinical sign associated with hypocalcaemia and should not be overlooked when investigating these cases.

Dogs suffering from PLE are also prone to developing thrombo-embolic disease as a complication of gastrointestinal loss of another blood protein, antithrombin! Dyspnoea or sudden death may be seen with pulmonary embolism and acute oedema of a limb and/or acute posterior paresis can be seen with other thrombo-embolic events.

Dr Armstrong treats her cases of PLE with a low dose of aspirin (0.5- 1mg/kg/day) for its antithrombotic effect but she states this may still not be adequate to prevent a thrombo- embolic event.

In some cases, determining whether the loss of albumin is via the gastrointestinal tract can be very difficult with no history or laboratory findings indicating PLE. Dr Armstrong suggests carrying out a faecal alpha1 proteinase inhibitor (a1- PI) test performed on samples of faecal samples collected on three consecutive days. Alpha1-PI is a plasma protein which is lost in the gastrointestinal tract at the same rate as albumin. 

Albumin is degraded by enzymes within the gut and is therefore not present within faeces. However, a1-PI resists degradation by digestive and bacterial proteinases within the gastrointestinal tract and its presence in excess in faeces is a good indicator of protein loss through the gastrointestinal tract.

Intestinal lymphangiectasia

Lymphangiectasia causes PLE and is characterised by dilation of lymphatics and leakage of lymph from villi. Yorkshire Terriers are a breed predisposed to lymphangiectasia and have a 10:1 odds ratio of developing this condition compared with other breeds.

In a study performed on Yorkshire terriers with intestinal lymphangiectasia, two thirds had diarrhoea and one third of cases had no signs of diarrhoea at all. This reiterates the point made earlier by Dr Armstrong that PLE cannot be ruled out based on the lack of clinical signs alone.

Congenital lymphangiectasia can be seen but more often lymphangiectasia is secondary to disease which causes an increase of hydrostatic pressure within lymphatic vessels. This could be due to inflammatory and neoplastic conditions such as inflammatory bowel disease (IBD) and lymphoma respectively.

It is important to remember that an increase in venous pressure can also cause this effect and may be seen in dogs with conditions such as right sided heart failure and pericardial effusion.

Ultrasound can be very useful in these cases as intestinal hyperechoic mucosal striations can be seen associated with lacteal dilation. These present as vertical linear striations within the gut wall and studies have shown a 96% positive association between mucosal striations and lymphangiectasia. There is also a 78% positive association with clinical PLE.

Dr Armstrong also wanted to point out that lymphangiectasia cannot be reliably recognised endoscopically – it provides only 68% sensitivity and 42% specificity.

This means intestinal biopsies are always necessary to make a definitive diagnosis. She prefers endoscopic biopsy, when possible, over surgical biopsies because of the risk of impaired wound healing and infection in hypoproteinaemic animals.

Treatment

Diet is key to treatment and Dr Armstrong advises using an ultra- low fat diet which is palatable, high in protein and has a high calorific density. She also advises feeding an unlimited amount at least two to three times a day. Novel protein diets may also be used successfully.

Treatment of concurrent disease such as IBD is also crucial. Prednisone at a dose of 1-2mg/kg/day or 30mg/m2 in larger dogs. Early adjunctive treatment with the immunosuppressive drug, cyclosporine, at a dose of 5mg/kg/day should also be considered, especially in dogs with ascites or pleural effusion.

If the side effects associated with prednisone are not well tolerated, an alternative steroid, budesonide (Entocort) should be the drug of choice. It has excellent mucosal effects and has a high percentage metabolism of first pass through the liver allowing the avoidance of many side effects associated with steroids.

For these reasons, Dr Armstrong considers this the treatment of choice, especially since a recent paper confirmed it has equivalent efficacy to prednisone therapy.

Oedema and cavitory effusion also need to be managed. Judicious use of spironolactone can be helpful but if ineffective, low dose furosemide will need to be added. If symptomatic pleural effusion is present, thoracocentesis may be necessary.

However, Dr Armstrong advises not rushing in to perform therapeutic abdominocentesis unless the pressure of the fluid within the abdomen is physically impeding respiration. If abdominocentesis is performed, there is a chance that fluid could leak at the site of aspiration, forming a plaque of fluid along the ventral abdomen and even down the hind and forelimbs, which could predispose to infection.

It is also important to manage other deficiencies including low calcium and cobalamin. Treatment of symptomatic hypocalcaemia should be with IV calcium therapy and/or oral calcitriol. Low cobalamin levels can be treated with subcutaneous injections of vitamin B12 at a dose of 250-1,500mcg per week. As discussed previously, low dose aspirin can also be administered to minimise the risk of thrombo- embolism.

Summary

Dr Armstrong led an extremely interesting and informative webinar providing great tips on how to diagnose and manage cases of PLE associated with lymphangiectasia.

There were some very important take-home messages including never ruling out PLE based on a lack of overt gastrointestinal signs, and also to take on board the more unusual signs seen with PLE such as facial irritation caused by hypocalcaemia.

Once again, this report really doesn’t do justice to Dr Armstrong’s comprehensive webinar covering protein losing enteropathy and this really is one of those webinars you must not miss out on.