The Clinical Utility of Specific Canine Pancreatic Lipase (Spec cPL™) Dr Remo Lobetti BVSc MMedVet(Med), ECVIM(CA) Bryanston Veterinary Hospital, 011 706 6023 AND Dr Liesel van der Merwe BVSc (Hons) MMedVet (Med) Small Animals.)

Pancreatitis is a relatively common disease with very
non-specific clinical signs such as abdominal pain,
anorexia, vomiting and diarrhoea. Currently there is
no very specific and sensitive test available to use as
a gold standard for diagnosis. Pancreatitis may present
as acute and fulminant or be more low grade
and chronic in nature. These forms will present with
different clinical signs and also cause a different degree
of cell damage and resultant lipase release by
the affected organ, depending on the degree of inflammation,
amount of fibrosis and number of cells
remaining and affected.
In a case series of canine random consecutive post
mortems the most common pancreatic lesion was
hyperplastic nodules (80.2%), followed by lymphocytic
inflammation (52.5%), fibrosis (49.5%), atrophy
(46.5%), neutrophilic inflammation (31.7%), pancreatic
fat necrosis (25.7%), pancreatic necrosis (16.8%), and
oedema (9.9%). The most common lesion, lymphocytic
inflammation, was mild in most cases. This could
help explain why histologic lesions may be more prevalent
than clinical signs of pancreatic disease.5
Clinically normal dogs have low circulating concentrations
of pancreatic lipase in the blood. On the other
hand, dogs with acute pancreatitis typically show dramatic
elevations in serum pancreatic lipase concentrations,
which remain elevated for a prolonged period.
Animals with low-grade, histopathological disease
may not show any dramatic elevations in serum lipase
and may even exhibit no clinical signs.5 Pancreatitic
lipase can be determined by either the spec cPL or
SNAP cPL test. The former is a laboratory run test,
whereas the latter is a point-of-care in-house test.
Spec cPL is generally considered the most sensitive
and specific test currently available for pancreatitis as
the specific lipase only occurs within pancreatic tissue,
as it is an enzyme that is synthesized and released
only by the pancreatic acinar cell. Assays that measure
PLI are species-specific. However, no test is perfect and the spec cPL can give both false positives and
negative results.1
SNAP cPL should be performed in any dog with acute
signs of gastrointestinal disease which does not have
an obvious diagnosis such as intestinal parasites, foreign
body, Parvo-virus infection, etc. The SNAP test
only gives either a negative or positive result and is
slightly more sensitive but less specific than the Spec
cPL. If the test is negative then pancreatitis can essentially
be ruled out as the sensitivity of the SNAP
is 93% which gives a 7% chance of a false negative.4
A positive SNAP cPL indicates a lipase value of ≥
200ug/L. However, as a positive Snap cPL, is NOT
a 100% diagnostic positive diagnosis for pancreatitis,
it is still the responsibility of the clinician to perform
a full diagnostic workup. Ideally an abdominal ultrasound
should be performed to exclude other abdominal
conditions which could cause similar clinical signs
and also cause lipase release.
In addition, measurement of Spec cPL should be done
to help confirm diagnosis of pancreatitis. The Spec
cPL is a quantitative test with 3 diagnostic ranges: normal
reference range (< 200 ug/L), questionable range
(between 200-400 ug/L), and diagnostic cut-off for
pancreatitis (≥ 400 ug/L) (IDEXX package insert). The
magnitude of elevation of serum canine pancreatic
lipase concentration does, however, not establish a
prognosis for a patient with acute pancreatitis nor is
there evidence that changes in serum concentrations
correspond to clinical improvement.1
The sensitivity of Spec cPL in various studies ranges
from 21% in dogs with histopathologically confirmed
mild pancreatitis; 71% in dogs with severe pancreatitis;
and up to 87% in some cases.4 It would appear that
the greater the pancreatic inflammation the greater
the test sensitivity, which would make sense as more
lipase is release into the bloodstream and these dogs
have more severe clinical signs thus the prevalence
in the test population is higher. Thus there is about a
15-25% possibility of having a false negative diagnosis.
The Spec cPL sensitivity has also been measured against an increase between > 200- 399 ug/L (90%)
and an increase > 400ug/L( 75%) thus it decreases as
the cutoff increases – but the specificity will increase
with an increased cutoff. The specificity is 74% for the
SNAP, 72% for Spec cPL cutoff between 200 -399ug/L
and 78% with a cutoff > 400ug/L.4
Spec cPL cannot differentiate between primary and
secondary pancreatitis — some dogs with an inflammatory
disease process in another organ in the region
of the pancreas (liver, gall bladder, mesentery, peritoneum)
may have secondary pancreatic inflammation
and animals with primary intestinal disease (foreign
body, inflammatory bowel disease, lymphoma) may
show elevated lipase values.1,2
Two recent studies investigating risk factors for pancreatitis
showed that many dogs had co-existing disease
and that there appeared to be an association
between the presence of Cushing’s disease and the
development of pancreatitis. Dogs with Cushing’s
disease and no clinically diagnosed pancreatitis had
a higher Spec cPL concentrations and more positive
SNAP cPL results than clinically healthy dogs with
normal ACTH stimulation test results. Spec cPL test
concentrations were significantly higher in dogs with
Cushing’s disease (491.1 ug/L) than in healthy dogs
(75.2 ug/L), with more abnormal Spec cPL results
in Cushing’s dogs. There were more positive SNAP
results in dogs with Cushing’s disease (55%) than in
healthy dogs (6%).3
In another study, SNAP cPL and Spec cPL was evaluated
in 3 groups of dogs: healthy dogs (n=20), those
with signs of Cushing’s disease but normal ACTH
stimulation test results (n=12), and dogs with confirmed
Cushing’s disease (n=20). Dogs were excluded
from the study if they had any clinical signs suggestive
of pancreatitis. Healthy dogs had one SNAP cPL positive
test and one Spec cPL in the 200-400g/L range.
In the second group, 3/12 dogs had a positive SNAP
cPL and 2 dogs had Spec cPL consistent with pancreatitis.
In dogs with confirmed Cushing’s disease,
11/20 had a positive SNAP cPL and 5 had a Spec cPL at the 200-400g/L range, and 7 had values >400g/L.
Yet none of the “positive” animals had clinical signs
consistent with pancreatitis.5 However, as it has been
reported that low grade pancreatitis can be present
as a post mortem histopathological diagnosis it is unknown
if these dogs had low grade clinical pancreatitis
(no biopsies were performed) or if something else
was causing the elevation in the lipase.3
Miniature Schnauzers with severe hypertriglyceridaemia
(> 9mmol/L, 900mg/dL) were 4.5x more likely
to have a Spec cPL value consistent with pancreatitis
(≥200 μg/L)4; however, these dogs did not show any
obvious clinical signs of pancreatitis.6
Pending further study, SNAP and Spec cPL test results
should be interpreted cautiously in dogs with Cushing’s
disease and hypertriglyceridaemia to avoid a
false diagnosis of concurrent pancreatitis.
In one study4, dogs were enrolled based on clinical
signs of pancreatitis and the study showed that the
SNAP test had a sensitivity of 91-94% and specificity
of 71 – 77%. Using a cutoff of 400ug/L the Spec cPL
had a sensitivity of 71-77% and a specificity of 80 –
85%.4 Another study also using a clinical diagnosis
(clinical, serum chemistry, abdominal ultrasound) of acute pancreatitis in a group of dogs presenting with
acute abdomen, the sensitivity of the SNAP cPL was
82% (18% chance of false negative result) and specificity
59% (41% false positive results).1 The false positive
result dogs may have had pancreatic inflammation
due to diffuse abdominal inflammation due to the
underlying disease process such as septic peritonitis,
conditions causing hypo-perfusion or reperfusion injury,
acute gastroenteritis, duodenal reflux and intestinal
foreign bodies. In that study, the Spec cPL had a
sensitivity of 70% and a specificity of 77% (23% false
positives) with the accuracy of the SNAP and Spec
cPL in animals with clinically diagnosed pancreatitis
calculated at 65% and 75%, respectively.
It is thus evident that is it important to have a positive
SNAP confirmed by the Spec CPL test at a laboratory.
Other conditions where Spec cPL is elevated include
Babesia rossi where 28% of hospitalised cases had a
level >400ug/L, patients with more advanced mitral
valve disease and heart failure had minor increases
(200 – 400 ug/L) and in and a small percentage of
dogs on phenobarbitone and potassium bromide
treatment which had increases between 200-400ug/
L in 13/310 cases and increases >400ug/L in 9/310
dogs.7,8,9.

Sensitivity of a test means “positivity in disease”, which means a sensitive test has no or few false negatives. The more
sensitive a test the more likely you are to get false positives if your test population is not properly selected.

Specificity means” negativity in health” – which means few or no false positive test results. The more specific a test is
the more likely you are to get a false positive in a poorly selected test population.

With the Spec cPL test: We know that histopathological pancreatic inflammation is present in many animals, which
have mild or no signs of disease. So if we use histopathological changes as the gold standard for pancreatitis the
test may be very specific (very few false positives) but if we were to use “clinically confirmed” pancreatitis using best
available clinical, biochemistry and abdominal ultrasound evidence as our gold standard the specificity will be lower,
more positives in the absence of clinical disease. This makes sense as we know some animals walk around with mild
inflammation and no clinical signs. These numbers are not written in stone as they vary depending on what they are
measured against.

 

Take Home Message
• A negative SNAP test makes pancreatitis highly unlikely and thus consider other causes for the
clinical presentation.
• The Spec cPL and SNAP tests are more sensitive and specific in acute pancreatitis.
• Even if it is a true positive result and the dog does have pancreatitis, it does not mean that it is the
only condition present. Pancreatitis can be both primary and secondary and neither the SNAP
nor the Spec cPL can differentiate between the two. Secondary causes of pancreatitis such as
septic peritonitis or intestinal foreign body will need to be specifically addressed. These tests are
meant to be PART of the diagnostic evaluation and not the initial test to place the patient into a
pancreatitis positive/negative group.
• There are some other disease conditions which appear to cause false positive results and thus
decrease the specificity of the test. Cushing’s disease, chronic glucocorticoid treatment and
elevated triglycerides in Miniature Schnauzers have been shown to cause increased numbers of
positive Snap and Spec cPL results in the absence of clinical pancreatitis. Thus a positive SNAP
and Spec CPL is not diagnostic for pancreatitis.

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