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WORLD GASTROENTEROLOGY NEWS APRIL 2018
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Appropriate use of Fecal Calprotectin
VG Naidoo, MD
Principal Specialist
Department of Gastroenterology; Nelson R Mandela School of
Medicine, University of KwaZulu-Natal
Durban, South Africa
Introduction
In patients presenting with chronic
gastrointestinal symptoms, distinguishing
between functional and
organic disorders is essential. Assessing
for markers of inflammation such as
an erythrocyte sedimentation rate or
C-reactive protein may help select patients
for further investigation to rule
out organic disease. However, these
are tests of systemic inflammation and
not gut specific. The emergence and
availability of fecal calprotectin (FC)
as a non-invasive test of intestinal
inflammation places great power in
the hands of clinicians. However, with
great power comes great responsibility.
Every diagnostic test ordered has
cost implications that nibble away
at the finite healthcare budget. It is
thus imperative that whenever a new
test finds its way into daily practice,
clinicians should receive guidance regarding
its appropriate use. This is of
particular importance in resource-limited
settings. This paper will focus on
the appropriate use of FC in patients
with suspected diarrhea predominant
irritable bowel syndrome (IBS) and
as a monitoring tool in patients with
inflammatory bowel disease (IBD).
FC in general practice
Primary care physicians are often
the first port of call for patients with
symptoms suggestive of IBS. Distinguishing
these symptoms from early
IBD can be challenging and IBS to a
degree remains a diagnosis of exclusion.
Clinical skill and judgement
remain the most cost effective diagnostic
modality. FC is a useful screening
test to select patients for specialist
referral and potentially avoid unnecessary,
invasive and expensive endoscopic
examinations. A combination of low
C-reactive protein (CRP) and fecal
calprotectin makes IBD unlikely.1 This
potentially reduces the procedure load
on endoscopy services.2 Additionally,
it provides the primary care physician
with an objective degree of reassurance
of not having overlooked serious bowel
pathology. However, it should not
replace traditional clinical evaluation
that includes an assessment for alarm
features. Patients with IBS symptoms
or altered bowel habit that have alarm
symptoms or other features such as
iron deficiency anemia, weight loss and
/ or blood in their stools do not require
FC testing. If an appropriate indication
for endoscopic examination exists then
fecal calprotectin becomes superfluous
and is an unnecessary additive expense
to the diagnostic work-up. Thus, if
a clinician has already decided that
endoscopic examination is warranted
then FC testing is not required.
In a British primary care study of
962 patients (18 to 45 years of age)
with persistent gastrointestinal symptoms,
using a FC cut-off of 50mg/g
yielded a negative predictive value
of 98% and positive predictive value
of 28% for organic disease.3 Three
percent of patients with a negative
FC using this low cut-off value had
organic disease. Mild ulcerative colitis
(proctitis only) and celiac disease
accounted for most of the false negative
results. Overall, there was a low
prevalence of organic disease in this
study population and increasing the
cut-off value to 150mg/g would have
improved the positive predictive value
to 71% but at the cost of a slight
reduction in negative predictive value.
It is not clear what the appropriate
cut-off value should be in different
populations. In general, accepting
a cut-off value of 50mg/g ensures a
high sensitivity. A Ugandan study in
children found FC levels comparable
to those reported in the developed
world.4 There is a need for further research
in developing countries where
there is a higher burden of infectious
diseases such as HIV, tuberculosis and
parasites to help define the role of FC
use in these contexts.5, 6
False positives and negatives
FC has a false positive rate of up to
9% based on negative upper and lower
gastrointestinal endoscopic findings
in patients with elevated FC without
taking into account the possibility of
significant small bowel pathology.7 A
small bowel video capsule study of 55
patients labelled as having false posi-
FC is a useful screening
test to select patients
for specialist referral
and potentially avoid
unnecessary, invasive
and expensive endoscopic
examinations.