Diagnostic Value of Calprotectin in Irritable Bowel Syndrome
and in Inflammatory Bowel Disease
C. GRAD1, LILIANA DAVID1, P. PORTINCASA2, D.L. DUMITRAŞCU1
1“Iuliu Haţieganu” University of Medicine and Pharmacy, 2nd Medical Clinic, Cluj-Napoca, Romania
2“Aldo Moro” University, “A. Murri” Clinica Medica, Dept. of Interdisciplinary Medicine (DIM), Bari, Italy
The inflammation is an important component of the bowel wall structure. The amount of
inflammation is gradually increased from normal state, to functional bowel disorders and to
inflammatory bowel disease. Calprotectin is a recently established marker for intestinal inflammation.
This paper surveys the present knowledge on fecal calprotectin testing as predictor of intestinal
inflammation. We also show on a sample of patients that inflammation as tested with fecal
calprotectin test may also be found, in lower degree, in irritable bowel syndrome. In inflammatory
bowel disease, the calprotectin fecal test shows higher intensity values.
Key words: Calprotectin, fecal test, inflammation, inflammatory bowel disease, irritable bowel
Irritable bowel syndrome (IBS), which has
abdominal pain as its cardinal symptom, is one of
the most common functional gastrointestinal disorders,
with an estimated prevalence of 8–22% in the
general population .
Despite a number of biological triggers for
the onset of IBS have been proposed, including
bacterial gastroenteritis and alterations of gut
microflora , the pathophysiology of IBS remains
uncertain. Hereditary and environmental factors are
likely to play a role . Many studies have reported
abnormal gastrointestinal motility, visceral hyper-
sensitivity, psychologic dysfunction, and emotional
stress in patients with IBS. Results, however, have
often been conflicting and no organic, functional or
psychological abnormality has been found to be
specific for this disorder.
Microscopic inflammation – detailed immuno-
histologic investigation has revealed mucosal immune
system activation in a subset of patients with IBS
(mostly those with the diarrhea predominant type)
. Similar observations have been made in patients
with presumed postinfectious IBS, suggesting a
possible common link. A study in which full-thickness
jejunal biopsies were obtained in 10 patients with
severe IBS found increased lymphocyte infiltration
in the myenteric plexus in 9 patients and neuron
degeneration in 6 patients . The extent to which
such abnormalities might contribute to the patho-
genesis of IBS in the general population remains
unclear as only a small number of patients have
been studied. Furthermore, most of patients were
studied in tertiary referral centers. Other studies
have demonstrated a correlation between abdominal
pain in IBS and the presence of activated mast cells
in proximity to colonic nerves .
The development of IBS following infectious
enteritis has been suspected clinically based upon a
history of an acute diarrheal illness preceding the
onset of IBS in some patients . Presence of
abnormal bacterial flora in the feces, signs of chronic
inflammation in the intestinal mucosa, positive
lactulose breath test and beneficial effect of
probiotics and antibiotics serve as a proof of the
bacterial etiology in postinfectious IBS . Few
controlled studies have investigated this topic in
detail, but persistent IBS have been noted in
approximately 10 to 30 percent of patients after
acute bacterial infection [11–14].
The role of chronic inflammation in the
pathophysiology of postinfectious IBS is underlined
by the presence of lymphocytic infiltration in the
intestinal mucosa and of increased expression of
inflammatory components in intestinal mucosa and
blood (cytokines, mastocytes and serotonin) .
Interleukin 8 is an important modulator of
the inflammatory process. Its activity is inhibited
by its natural antagonist IL 1. The equilibrium
between these two cytokines is the one dictating
the biological disponibility of the IL 8 and its
contribution to the inflammation. The expression of
IL 8 was enhanced during the acute infection and it
continued to be increased in the patients who
suffered from postinfectious IBS compared to
ROM. J. INTERN. MED., 2012, 50, 1, 3–6
4 C. Grad et al. 2
patients who did not develop IBS and presented
with decreased level of cytokines after the acute
Enteroendocrine cells in patients with post-
infectious IBS appear to secrete high levels of
serotonin. These patients have postprandial increased
serotonin levels compared to healthy individuals
and patients with IBS with constipation who have
normal levels of serotonin after meals .
Mastocytes have a role in increasing intestinal
mucosa permeability – a phenomenon that has been
also reported in postinfectious IBS patients. The
increased permeability implies a disruption of
normal barrier, which allows bacteria to invade in
lamina propria and provides a mechanism for
Assessing the presence and degree of intestinal
inflammation objectively, simply, and reliably is a
significant problem in gastroenterology. For assessing
intestinal inflammation it can be used an immuno-
histologic exam and also fecal calprotectin and
fecal lactoferin as non-invasive methods.
Calprotectin is a zinc and calcium binding
protein that is derived mostly from neutrophils and
monocytes with antimicrobial and antiproliferative
activities . It can be detected in tissue samples,
body fluids, and stools, making it a potentially
valuable marker of neutrophil activity . Initial
studies show that fecal calprotectin levels are increased
in intestinal inflammation and may be useful for
distinguishing inflammatory from noninflam-
matory causes of chronic diarrhea [20–22]. Other
potential roles have also been proposed for
calprotectin, including colorectal cancer screening
[23–25], follow-up of inflammatory bowel diseases.
Normalization of fecal calprotectin seems to be a
strong indicator of mucosal healing. Fecal calprotectin
values can be used to evaluate the response to
treatment, to screen asymptomatic patients ,
and to predict inflammatory bowel disease relapses
. Fecal calprotectin correlated closest with
Simple Endoscopic Score for Crohn’s disease
(SES-CD), followed by CRP, blood leukocytes,
and the Crohn’s disease activity index (CDAI).
Furthermore, fecal calprotectin was the only marker
that reliably discriminated inactive from mild,
moderate, and highly active Crohn’s disease, which
underlines its usefulness for activity monitoring
Calprotectin level of greater than 10 mg/L
was most useful in the prediction of organic disease
with a sensitivity of 89%, and a specificity of 79%.
Elevations in calprotectin and lactoferrin are seen,
not only in IBD, but in other organic gastro-
intestinal diseases such as diverticular disease,
infectious enterocolitis, nonsteroidal antiinflam-
matory drug (NSAID) enteropathy, and cancer.
Stool markers are appropriate, then, as a screening
test to determine which patients with gastrointestinal
symptoms require further invasive testing as opposed
to those with likely IBS or functional disease. This
is perhaps most useful in the pediatric patients in
whom invasive testing is more difficult to perform;
several studies suggest that calprotectin may be
useful in this patient group .
With a cut-off point of 30 mg/L fecal cal-
protectin has100% sensitivity and 97% specificity
in discriminating between active Crohn’s disease
and IBS .
Taking into account these aspects, we assessed
fecal calprotectin in patients with IBS and IBD and
results were correlated with the presence of small
intestinal bacterial overgrowth (SIBO). Forty
patients with IBS (28 females, 12 males, mean age
43 ± SD15 yrs), diagnosed according to Rome III
criteria (3) [REF], were investigated by fecal
calprotectin with a semiquantitative commercially
available test (SOFAR, Trezzano Rosa, Italy). A
group of 20 sex- and age-matched patients with
inflammatory bowel disease (IBD) served as control
(15 ulcerative colitis, 3 Crohn, 2 unspecific IBD) (8
females, 12 males, 47 ± 13 yrs). IBS patients were
tested for SIBO with the oral glucose and lactulose
H2 breath test, according to previously published
The results showed that Calprotectin test was
positive in all 20 IBD patients with 16/20 (80%)
with severe inflammation. In IBS, calprotectin was
mildly positive in 14/40 (35%) patients (p < 0.01
vs. IBD). The prevalence of SIBO was significantly
greater in IBS patients with intestinal inflammation
than in IBS patients without intestinal inflammation
(71% vs. 8%, respectively, p < 0.001), as assessed
by calprotectin test.
As a conclusion we can state that fecal
calprotectin is a test which can differentiate
between IBD and IBS patients. SIBO is associated
with mild intestinal inflammation in IBS, as
suggested by calprotectin fecal test.
Fecal calprotectin has been proposed as a
non-invasive surrogate marker of intestinal
inflammation in inflammatory bowel disease. A close
3 Diagnostic value of calprotectin in irritable bowel syndrome and in inflammatory bowel disease 5
correlation between fecal calprotectin concentration
and fecal leukocyte excretion quantified with 
indium has been described. This fecal marker can
be detected using simple and cheap techniques.
Fecal calprotectin has a good diagnostic precision
for separating organic and functional intestinal
diseases. However, the specificity for the diagnosis
of inflammatory bowel disease is lower than desirable,
as several diseases other than inflammatory bowel
disease, specially colorectal neoplasia and gastro-
intestinal infection, can also increase fecal calprotectin.
High concentration of calprotectin in feces is a
strong argument to carry out a colonoscopy in
order to rule out the presence of inflammatory
bowel disease or other organic diseases. A parallelism
Inflamaţia reprezintă o componentă importantă a structurilor parietale
intestinale. Cantitatea de inflamaţie este crescută treptat, de la starea normală, la
tulburările funcţionale intestinale şi la bolile inflamatorii intestinale. Calprotectina
este un marker al inflamaţiei intestinale recunoscut relativ mai recent. Această
lucrarea prezintă cunoştinţele actuale despre testarea calprotectinei fecale pentru
inflamaţia intestinală. Arătăm de asemenea că inflamaţia, determinată cu testul
fecal de calprotectină, se întâlneşte, în grad redus, în intestinul iritabil. În bolile
inflamatorii intestinale, testul fecal de calprotectină arată nivele crescute ale
intensităţii inflamaţiei intestinale.
between faecal calprotectin levels and inflammatory
bowel disease activity has been confirmed, although
this fecal marker appears to better reflect the
disease activity in ulcerative colitis than in Crohn’s
disease. Fecal calprotectin’s capacity to predict
inflammatory bowel diseases relapse is promising.
It has been suggested that in inflammatory bowel
disease patients receiving treatment, a normalization or
decrease in fecal calprotectin concentrations is an
accurate indicator of endoscopic healing. A greater
fecal calprotectin concentration has been shown in
asymptomatic first-degree relatives of patients with
inflammatory bowel disease, suggesting that there
is a high prevalence of subclinical intestinal in-
flammation in them .
Corresponding author: D.L. Dumitraşcu, Professor
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Received December 20, 2011