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.
