This study aimed to estimate the prevalence of celiac disease in adult Saudi patients with irritable bowel syndrome (IBS) symptoms. 320 patients meeting IBS criteria underwent testing for celiac disease markers. 15 patients (4.69%) tested positive for at least one marker. These patients reported more frequent gastrointestinal symptoms. Nutritional parameters like hemoglobin and albumin were lower in positive patients and improved with a gluten-free diet. 11 of the 15 positive patients were diagnosed with celiac disease via biopsy. The results suggest minimally symptomatic celiac disease can be mistaken for IBS, and screening this patient group may help manage their symptoms.

1. Prevalence of Coeliac Disease in Adult Saudi
Patients with Symptoms of Irritable Bowel
Syndrome; pilot study.
Shendy M. Shendy* and Nihal Al-Assaly** , Naema I. El-Ashry**.
*Tropical, Hepatology and gastroenterology department, **Clinical biochemistry
dep, Theodor Bilharz research Institute.
-Accepted for publication in Journal of Arab Society for Medical
Research (JASMR), 29- 12- 2006
Abstract
Few recent studies have found higher prevalence of coeliac disease among
patients with diagnosis of irritable bowel syndrome (IBS) than general population (3-
11% vs. 0.2-0.6%). Similar studies showed that coeliac disease is as common in
Middle Eastern countries as in Europe; in both the general population and at-risk
groups. The aim of this work is to estimate the prevalence and the potential clinical
consequences of coeliac disease testing in adult Saudi patients with IBS. Materials
and methods: This is a prospective pilot study including 320 Arab patients with
features compatible with IBS as defined by Rome III criteria without any other co-morbidity.
The age of patients ranged between18-70 years. All patients were
subjected to good history taking, clinical examination, and some investigations if
needed such as stool, urine, CBC, liver enzymes, kidney function tests, ECG,
electrolytes, H pylori serology, upper and lower endoscopy when indicated. Those
diagnosed as having persistent criteria of IBS were tested for coeliac disease by IgA
and IgG anti-gliadin antibodies, anti endomysial antibodies (EMA) IgA and anti-TG2
(IgA and IgG). Upper endoscopy and duodenal biopsies were done and gluten free
diet was implemented for only those with positive serological test. The same tests
were repeated after period of about 6 months. Results: Anti-gliadin antibodies were
found positive in 15/320(4.69%) patients (14 with IgA and 13 IgG), EMA IgA in
13/320 (4.06%), anti-TG2 IgA in 12/320 (3.76%) and anti- TG2 IgG in 13/320
(4.06%). Abdominal pain, diarrhea, dyspepsia, postprandial distress, epigastric pain,
distension and chronic diarrhea were significantly higher and more common in
combinations in those with positive serology in comparison to serologically negative
patients (P < 0.05). Haemoglobin level, serum iron, albumin and calcium were found
to be significantly lower in those with positive serology in comparison to
serologically negative patients (P < 0.05). All these parameters improved
significantly after gluten free died (GFD) for about 6 months (P< 0.05). Only 11
patients (74.44% of those with positive serology and 3.49% of total patients) were
diagnosed by biopsies as compatible with coeliac disease of which, two patients have
family history of coeliac disease in first degree relatives. After gluten free died

2. (GFD) for about 6 months, seroconversion to negative tests occurred in 6 patients for
AGA-IgA, 4 for AGA- IgG, 3 for EMA IgA, 5 for Anti-TG2 IgA and 5 for Anti-TG2
IgG. Also, the grade of histopathology showed complete healing in 4 patients and
improvement to lower grades in 4 patients after GFD. Worsening occurred in one
case and still 7 cases showed the same grade of the disease. Conclusion: It is
concluded from this study that minimally symptomatic coeliac disease can easily be
mistaken for IBS. The presence of many persistent gastrointestinal symptoms in
addition to the lower serum levels of some nutritional parameters must alert the
physicians to screen for coeliac disease. Any serological test can be used for the
screening but this must be confirmed by tissue diagnosis which is the gold standard
for diagnosis. Finally, screening for coeliac disease among patients with IBS must be
considered to offer better prognosis to these patients simply by gluten free diet.
Introduction:
Irritable bowel syndrome (IBS) is a highly prevalent, multi-symptomatic,
gastrointestinal motility disorder that has a wide clinical spectrum. This disease
is associated with gastrointestinal dysmotility and/or visceral hypersensitivity.
Recent studies suggest that the prevalence of coeliac disease, a gluten-sensitive
enteropathy characterized by intestinal villous blunting and
malabsorption, is 3-11% among patients diagnosed with IBS, compared with
0.02-0.65% in the general population. Coeliac disease may be present in patients
with IBS-like symptoms with diarrhoea or constipation predominance, or
alternating bowel habit. Recent studies showed that coeliac disease is as
common in Middle Eastern countries as in Europe; in both the general
population and at-risk groups, e.g. patients with irritable bowel syndrome or
type 1 diabetes. Also, these studies showed that presentation with non-specific
symptoms or no symptoms is as common in the Middle East as in Europe
Measurement of IgA antibody to human recombinant tissue transglutaminase
(TTG) is recommended for initial testing for CD. Although as accurate as TTG,
measurement of IgA antibody to endomysium (EMA) is observer dependent and
therefore more subject to interpretation error. It is recommended that
confirmation of the diagnosis of CD require an intestinal biopsy in all cases.
Because the histologic changes in CD may be patchy, it is recommended that
multiple biopsy specimens be obtained from the second or more distal part of
the duodenum. There is good evidence that villous atrophy (Marsh type 3) is a
characteristic histopathological feature of CD (34). The presence of infiltrative
changes with crypt hyperplasia (Marsh type 2) on intestinal biopsy is
compatible with CD but with less clear evidence. The presence of infiltrative
changes alone (Marsh type 1) on intestinal biopsy is not specific for CD in
children. Concomitant positive serological tests for CD (TTG or EMA) increases

3. the likelihood such an individual has CD. In circumstances where the diagnosis
is uncertain additional strategies can be considered, including determination of
the HLA type, repeat biopsy or a trial of treatment with a gluten-free diet
(GFD) and repeat serology and biopsy. The diagnosis of CD is considered
definitive when there is complete symptom resolution after treatment with a
strict GFD in a previously symptomatic individual with characteristic histologic
changes on small intestinal biopsy. A positive serological test that reverts to
negative after treatment with a strict GFD in such cases is further supportive
evidence for the diagnosis of CD.
Our aims were to estimate the prevalence and the potential clinical
consequences of coeliac disease testing in adult Saudi patients with IBS.
Materials and methods:
This is a prospective pilot study evaluating adult patients attending GIT
outpatient clinic in Riyadh city in SA. Those patients with symptoms suggestive
of IBS and those also diagnosed after exclusion as IBS were included in the
study. The study included 320 patients. All patients were Arabs. They were 184
males and 136 females. Their age ranged from 18-67 years. They were chronic
patients attending the clinic for more than 6 months complaining of abdominal
pain with features compatible with IBS as defined by Rome III criteria.
Exclusion criteria:
1- Those with age below 18 years or above 70 years
2- Presence of red flag signs or alarm features as severe unrelenting
diarrhoea, nocturnal symptoms, unintentional weight loss, haematochezia, a
family history of organic gastrointestinal diseases such as IBD, celiac sprue or
malignancy
3- Symptoms or signs of coeliac disease or those already on gluten free
diet being diagnosed already as coeliac disease.
4- Those with other medical illnesses or on chronic medications for
organic disease.
5- Those who did not agree to continue follow up and giving consent to
study.
6- Females during pregnancy or breast feeding
All patients were subjected to good history taking, clinical examination, and
some investigations if needed such as stool, urine, CBC, liver enzymes, kidney
function tests, ECG, electrolytes, H pylori serology, upper and lower endoscopy
when indicated. Those with mixed or atypical presentation were investigated
properly for other diagnoses and then managed accordingly. Those diagnosed as
having persistent criteria of IBS were included in the study. As serological tests

4. and small bowel biopsy remain the cornerstones of diagnosis of coeliac disease
(23), these patients were subjected to:
1- Serum IgA and IgG anti-gliadin antibodies (AGA), Anti endomysial
antibodies (EMA) IgA (The test result is reported simply as positive or
negative, since even low titers of serum IgA endomysial antibodies are
specific for CD) and Anti-TG2 (IgA and IgG).
2- Upper endoscopy for those with positive serology and histopathology of
duodenal biopsy.
3- Gluten free diet for those with positive serology.
4- All the above tests were repeated after period of 6-12 months.
During endoscopy of patients with any positive serological tests, 4 to 6
duodenal biopsies were obtained. An experienced pathologist who was blinded
to the patient’s history and antibody assay results assessed the mucosal biopsy
sections for pathologic features of CD. Diagnosis of CD was made when there
were an increased number of intraepithelial lymphocytes with associated
subtotal or total villous atrophy (32). Histological grading was done according the
conventional system which grades the mucosal findings as normal, slight partial
villous atrophy, marked partial villous atrophy, subtotal and total villous
atrophy and Marsh system (34) which classified the histological changes of CD as
Type 0 or preinfiltrative stage (normal), Type 1 or infiltrative lesion (increased
intraepithelial lymphocytes), Type 2 or hyperplastic lesion (Type 1+
hyperplastic crypts), Type 3 or destructive lesion (Type 2 + variable degree of
villous atrophy) and Type 4 or hypoplastic lesion (total villous atrophy with
crypt hypoplasia). Type 3 has been modified to include Type 3a (partial villous
atrophy), Type 3b (subtotal villous atrophy) and Type 3c (total villous atrophy)
(35).
Patients can be considered as one of two groups - 'silent' celiac disease when
the patients are symptom free and serologically negative but bear the hallmarks
of the disease on histological grounds, and 'latent' celiac disease when
serological tests are positive but there are no or minimal histological changes,
such as increased density of intraepithelial lymphocytes (IELs) (25).
Statistical analysis
Results were analysed using SPSS 12 for windows software.
This study included 320 patients; 184 males and 136 females. Age ranged from
18-56 years
Table 1: clinical presentation in all patients.
Complaints Males
N=184
Females
N=136
Total
N=320
Complaints Males
N=184
Females
N=136
Total
N=320
Abdominal pain
Frequent or loose stool
Hard or infrequent stool
Altered stool habits
Other stool abnormalities*
78
35
21
26
32
98
16
46
20
27
176
51
67
46
95
Dyspepsia
Postprandial distress.
Epigastric pain
Abdominal distension
Eructation.
Chronic Anorexia
52
38
64
41
18
4
22
18
47
45
21
11
74
56
101
86
39
15

5. Other stool abnormalities*: straining during a bowel movement ,urgency (having to
rush to have a bowel movement) , feeling of incomplete bowel movement or anorectal
obstruction, passing mucus (white material) during bowel movement , abdominal
fullness, bloating or swelling.
Table 2: clinical presentation in all patients according sero-positivity.
Complaints Serologically
negative
(n=305)
Serologically
positive
(n=15)
Complaints Serologically
negative
(n=305)
Serologically
positive
(n=15)
Abdominal pain
Frequent or loose stool
Hard or infrequent stool
Altered stool habits
Other stool abnormalities
164 (53.8%)
43(14.1%)
66(21.6%)
45(14.8%)
93(30.5%)+
12 (80.0%)*
8 (53.3%)*
1 (6.7%)
1 (6.7%)
2 (13.3%)
Dyspepsia
Postprandial distress.
Epigastric pain
Abdominal distension
Eructation.
Chronic Anorexia
64(21.0%)
55(18.0%)
91(29.8%)
87(28.5%)
34(14.1%)
11(3.6%)
10 (66.7%)*
11 (73.3%)*
10 (66.7%)*
9 (60.0%)*
5 (33.3%)*
4 (26.7%)*
Significantly higher in comparison to serologically negative (P < 0.05).
Table 3: clinical presentation in sero-positive patients before and after
Gluten Free Diet (GFD):
Complaints
Serologically positive (n=15)
Complaints
Serologically positive (n=15)
Before GFD After GFD Before GFD After GFD
Abdominal pain
Frequent or loose stool
Hard or infrequent stool
Altered stool habits
Other stool abnormalities
12 (80.0%)
8 (53.3%)
1 (6.7%)
1 (6.7%)
2 (13.3%)
3(20.0%) *
2(13.3%) *
2 (13.3%)
3 (20.0%)
4 (26.7%)
Dyspepsia
Postprandial distress.
Epigastric pain
Abdominal distension
Eructation.
Chronic Anorexia
10 (66.7%)
11 (73.3%)
10 (66.7%)
9 (60.0%)
5 (33.3%)
4 (26.7%)
4 (26.7%) *
2 (13.3%) *
3 (30.0%) *
2 (13.3%) *
1 (6.7%)
1 (6.7%)
* Significant decrease in the number of patients after GFD in comparison to
before GFD (P < 0.05).
Table 4: Haemoglobin, serum iron, and liver enzymes in serologically negative and
serologically positive patients before and after gluten free diet.
Factor Serologically negative
patients Serologically Positive patients
At diagnosis At diagnosis After GFD
Hb (g/dl) 14.53 ± 03.45 13.21 ± 3.72* 14.25 ± 3.25+
S. iron (μg/dl) 72.63 ± 29.32 55.65 ±23.72* 65.34 ±20.76+
ALT (units/dl) 25.61 ± 11.34 27.23 ± 13.52 26.53 ± 13.84
AST (units/dl) 22.16 ± 10.35 26.35 ± 11.72 24.73 ± 11.51
Alk. Phosphatase (U/dl)
* Significant differences in comparison with serologically negative patients at
diagnosis (P< 0.05).
+ Significant differences in comparison with serologically positive patients at
diagnosis (P< 0.05).
Table 5: Blood levels of albumin, calcium, cholesterol and triglycerides in
serologically negative and serologically positive patients before and after gluten free
diet.
Factor Serologically negative
patients Serologically Positive patients
At diagnosis At diagnosis After GFD
S. albumin (g/dl) 4.30 ± 00.65 3.51 ± 00.71* 4.22 ± 0.51+
S calcium (mg/dl) 10.13 ± 1.20 8.35 ± 1.41* 9.02 ± 4.52+
Blood Cholesterol
(mg/dl) 169.50 ±21.37 151.28±23.56 158.40±22.64
Triglycerides (mg/dl) 153.28 ± 32.62 146.53±28.35 150.24 ±23.52

6. * Significant differences in comparison with serologically negative patients at diagnosis (P<
0.05).
+ Significant differences in comparison with serologically positive patients at diagnosis (P<
0.05).
Table 6: the results of serology in all patients
Serological tests total Positivity Positivity (males) Positivity (female)
Anti-gliadin antibodies (IgA/G) 15/320 (4.69% 7 (2.19%) 8 (2.50%)
EMA IgA 13/320 (4.06%) 6 (1.88%) 7 (2.19%)
Anti-TG2 IgA 12/320 (3.76%) 5 (1.57%) 7(2.19%)
Anti- TG2 IgG 13/320 (4.06%) 6 (1.88%) 7 (2.19%)
Table 7: IgA and IgG anti-gliadin antibody titres in those with positive tests (15
patients):
IgA anti-gliadin titre IgG anti-gliadin titre
Optical density Number of patients Optical
density
Number of patients
At the diagnosis After GFD At the diagnosis After GFD
>0.875
0.75-0.875
0.625–0.75
0.5–0.625
0.375–0.5
0.25–0.375
0.125–0.25
0.0–0.125 (-)*
52133001
01122125
>1.0
0.9-1.0
0.8–0.9
0.7–0.8
0.6–0.7
0.5–0.6
0.4–0.5
0.3–0.4
0.1-0.3
0.0-0.1 (-)*
3221121102
0011013117
Titre is expressed as optical density. GFD: gluten free diet. 14 patients were positive for IgA,
and 13 were positive for IgG. Those who were negative for any of them are positive for the
other. * = negative values
Table 8: Serology and histopathology in all positive cases (Before/After GFD):
AGA EMA IgA Anti-TG2 Histopathology (Marsh
classification)**
IgA IgG IgA IgG At diagnosis After GFD*
12
3 +
456789
10
11+
12
13
14
15
Total
positivity
+/+
+/-
+/+
+/-
+/-
+/+
+/+
+/-
+/-
-/-
+/+
+/+
+/+
+/+
+/-
14/8
+/+
+/+
+/+
+/+
-/-
+/+
+/+
+/-
+/-
+/-
+/+
+/+
-/-
+/+
+/-
13/9
+/+
+/+
+/+
+/-
+/-
+/+
+/+
+/-
+/+
-/-
+/+
+/+
-/-
+/+
+/+
13/10
+/-
+/+
+/-
+/+
-/-
+/-
+/+
+/+
+/+
-/+
+/-
+/-
-/-
+/+
+/-
12/7
+/-
+/+
+/+
+/+
+/-
+/+
+/+
+/-
+/-
-/+
+/-
+/+
-/-
+/+
+/-
13/8
Type 1
Type2
Type3a
Type 1
Normal
Type3b
Type2
Type2
Type 1
Normal
Type1
Type2
Normal
Type2
Normal
11
Normal
Type 2
Normal
Normal
Normal
Type 2
Type 2
Type 1
Type2
Normal
Normal
Type 1
Normal
Type1
Normal
7

7. After gluten free died for about 6 months, seroconversion to negative tests occurred in 6
patients for AGA-IgA, 4 for AGA- IgG, 3 for EMA IgA, 5 for Anti-TG2 IgA and 5 for Anti-
TG2 IgG. * GFD: gluten-free diet. + these patients have family history of coeliac disease in
first degree relatives.
It is clear from these results that patients number 10, and 13 were only positive for one
test (IgG-AGA and IgA-AGA respectively) and patient number 5 is positive for three of the
five tests; IgA AGA, EMA and IgG anti-TG2. The three patients showed normal
histopathology in addition to patient number15. Thus, only 11 patients (74.44% of those
with positive serology and 3.49% of total patients) were diagnosed by biopsies as compatible
with coeliac disease. Two patients have family history of coeliac disease in first degree
relatives. One of them; patient number 3 was found to have positive serology for all tests
and type 3a histopathology. The other patient had similar serology but type 1
histopathology. All patients with positive serology were subjected to GFD for at least 6
months. Then all serological tests and tissue biopsies were repeated and showed some
improvement.
Table 9: Summery of histopathological findings in the 15 AGA positive patients:
Normal Positive histopathology
Type 1 Type 2 Type 3 Type 4 Total
At diagnosis 4 4 5 2 0 11 (74.44%)
After GFD 8 3 4 0 0 7 (46.67%)
The grade of histopathology showed complete healing in 4 patients and
improvement to lower grades in 4 patients (one type 3 changed to type 1 and 3
cases of type 2 changed to type 1). Worsening occurred in one case from type 1 to
type 2. 7 cases still showed type 1 or type 2 diseases.
It is concluded from this study that minimally
symptomatic coeliac disease can easily be mistaken for IBS.
The presence of many persistent gastrointestinal symptoms
in addition to signs and lower serum levels of some
nutritional parameters must alert the physicians to screen
for coeliac disease. Any serological test can be used for the
screening but this must be confirmed by tissue diagnosis
which is the gold standard for diagnosis of this disease.
Finally, screening for this disease among patients with IBS
must be considered to offer better prognosis to these patients
simply by gluten free diet.