Celiac disease in adult population in
Tuzla region of Bosnia and Herzegovina:
a 3-year surveillance (2007-2009)
Zoran Tosic1, Nermin Salkic2, Natasa Krizic2, Samed Djedovic3, Mirela Fijuljanin1,
Devla Barakovic1
General Hospital Brcko, Brcko, Bosnia and Herzegovina1
Department of Gastroenterology and Hepatology, University Clinical Center Tuzla,
Tuzla, Bosnia and Herzegovina2
BH Heart Center Tuzla, Tuzla, Bosnia and Herzegovina 3
Corresponding author: Zoran Tosic, MD. Department for Internal medicine, General hospital Brcko, Brcko, Bosna i Hercegovina. Phone: +387
66 801 457; Email: drtosic@gmail.com:
Abstract. Background: there is no epidemiological estimation of the incidence and
prevalence of CD in the adult population in Bosnia and Herzegovina (BiH), nor
there are reports about the clinical presentation of CDin patients in BiH. Aim: to
assess the epidemiological and clinical characteristics of CD in the adult
population in Tuzla Canton in northeast of Bosnia and Herzegovina. Methods: we
retrospectively analyzed all hospital records of both adult inpatients and
outpatients evaluated in University Clinical Center Tuzla, with suspected CD and
residing in Tuzla Canton of B&H between 1.1.2007 and 31.12.2009. Results:
during the 3-year period we registered 42 cases of celiac disease (CD) with 31/42
(73.8%) of female and 11/42 (26.2%) of male patients – male to female ratio 1 to
2.82. The average annual crude incidence of CD during the observed period was
2.55/105 population (%95 CI=1.74-3.36). The average crude incidence in men was
1.51/105 and 4.08/105 in women. The average annual standardized incidence
during the time period 2007-2009 was 1.89/105 (%95 CI=1.32-2.56).The sum
prevalence during the study period was 7.66/105 population. Prevalence among
men was 4.53/105 and 12.23/105among women. Conclusions: The incidence of
CD in our region is demonstrating a steep rise and apparently low prevalence in
our region is merely a result of poor availability of diagnostics in previous years.
Keywords: celiac disease, gluten enteropathy, epidemiology, incidence, prevalence,
Bosnia and Herzegovina.
1. INTRODUCTION
Celiac (coeliac) disease is a chronic disease which involves the small intestine and
caused by inadequate immune reaction in contact with glutenin genetically predisposed
people. Celiac disease was once considered a rare disease with a prevalence of 1 per
3345 residents. However, studies have shown a prevalence of 1 per 266 of residents
based on serological screening (1).
Although initially associated primarily with the children’s age, the disease can
clinically manifest at any age with high incidence registered even in the fifth or sixth
decade of life (2). It is estimated that in the Croatian pediatric population incidence of
celiac disease is 1.9 : 1000 births, while in adult population there are nearly 40000
unidentified patients with celiac disease (3). It is believed that the ratio of diagnosed
and undiagnosed cases of the disease in Europe is 1 to 5-13 residents, while there is a
reliable report that this ratio may be much higher in USA (1:53) (4, 5).
The true prevalence of celiac disease is difficult to grasp, because many patients
have atypical symptoms or no symptoms at all. According to available data, there is no
epidemiological estimation of the incidence and prevalence of celiac disease in the
adult population in Bosnia and Herzegovina(B&H), nor there are reports about the
clinical presentation of celiac disease in patients in B&H.
Therefore, we aimed to assess the epidemiological and clinical characteristics of
celiac disease in the adult population in Tuzla Canton in northeast of Bosnia and
Herzegovina.
2. PATIENTS AND METHODS
We retrospectively analyzed all hospital records of both inpatients and outpatients
evaluated in Department of Gastroenterology and Hepatology, Endoscopy Unit and
Department of Pathology in University Clinical Center Tuzla, with suspected celiac
disease and residing in Tuzla Canton of B&H between 1.1.2007 and 31.12.2009. We
included adult patients with age over 18 years. We excluded all patients that did not
reside in Tuzla Canton.
After that, we selected all patients with histological and serological confirmation
of celiac disease. We also recorded age, gender, date of initial diagnosis, clinical
representation, body mass index, presence of anemia and other relevant clinical
symptoms. We excluded patients with incomplete records.
3. STATISTICAL ANALYSIS
Statistical analysis was performed using SPSS 20.0 (SPSS, Chicago, IL, USA).
Descriptive statistics has been used for determination of baseline characteristics. The
year of diagnosis was used to date incidence. Calculations of incidence have been
performed based on the appropriate (December 31st, 2009) population estimates in our
region obtained from the Federal Office of Statistics, Federation of Bosnia and
Herzegovina, Sarajevo. Ninety five per cent confidence intervals (95% CI) of incidence
rates were estimated assuming a Poisson distribution of cases. Crude annual incidence
rates were calculated based on the number of patients diagnosed and the number of
inhabitants for both sexes while average incidence rate during observed period was
calculated based on number of study years. Age standardized incidence rates were
calculated using European standard population weights (4, 7, 11, 14, 22) for each of
our age group (6). Prevalence estimate during observed period was estimated based on
the total number of cases detected and the number of inhabitants according to latest
population estimates. Statistical level of 95% (p<0.05) was considered as significant for
all performed tests.
4. RESULTS
During the 3-year period we registered 42 cases of celiac disease (CD) with 31/42
(73.8%) of female and 11/42 (26.2%) of male patients – male to female ratio 1 to 2.82.
The median age in all patients with celiac disease was 36 years (interquartile range
29 to 42 years) with a range spanning from 19 to 58 years. There was no significant age
difference (t=0.10; df=40; p=0.92) between men (36±12 years) and women (36±10
years).
Clinical characteristics of celiac disease at the moment of detection are presented
in Table 1.
Table 1. Clinical characteristics of celiac disease in patients detected in Tuzla Canton from year 2007 to 2009
Clinical characteristics
N
Percentage
Anemia
25/42
59.5%
Body Mass Index below normal
27/42
64.3%
AGA antibodies present
39/42
92.9%
EMA antibodies present
41/42
97.6%
Comorbidities (hypothyreosis)
6/42
14.3%
Diarrhoea
35/42
83.3%
Abdominal cramps
4/42
9.6%
Weight loss
3/42
7.1%
Dominant symptom
The average annual crude incidence of celiac disease during the observed period
was 2.55/105 population (%95 CI=1.74-3.36). The average crude incidence in men was
1.51/105 and 4.08/105 in women. After we performed standardization according to
standard European population, the average annual standardized incidence during the
time period 2007-2009 was 1.89/105 (%95 CI=1.32-2.56). The sum prevalence during
the study period calculated for population numbers on 31.12.2009, was 7.66/105
population. Prevalence among men was 4.53/105 and 12.23/105 among women.
The annual incidence for men and women and complete sample is depicted in
Figure 1. As demonstrated incidence rates are demonstrating steady increase.
Figure 1. Annual incidence of celiac disease in Tuzla region of Bosnia and Herzegovina during the period
2007-2009 in both gender and complete sample.
The graphic display of incidence according to gender and age is presented in
Figure 2. The largest incidence was found in women age 26-35, while peak incidence
in men was in older age group of 36-45.
Figure 2. Incidence of celiac disease according to age at the time of diagnosis and gender of the patient.
5. DISCUSSION
Until the late 1970s global prevalence of celiac disease was greatly underestimated
with reported rates of 0.03% in general population (7). Nowadays, estimated
prevalence in general population in Europe and USA is around 1%, ranging from 0.5 to
1.26% (8). Approximately 3 million people in Europe and another 3 million people in
the United States are estimated to be affected by celiac disease with higher prevalence
in European countries with temperate climates.
Although the actual occurrence of celiac disease has been underestimated for years,
the prevalence of the disease is increasing, mainly due to the advances in diagnostic
methods and improvements in screening. This is especially valid for developing
countries such as Bosnia and Herzegovina. Unfortunately, as with many other
conditions, the data about epidemiology of celiac disease in Bosnia and Herzegovina is
non-existing and this is valid for both pediatric and adult population. The
improvements of diagnostic tools along with the improved awareness especially in the
adult population are producing increasing number of patients – number that we don’t
know about. Therefore it was our intention to make as accurate assessment of the
epidemiology of celiac disease in adult population in a well-defined region of Bosnia
and Herzegovina.
Of course, it is not possible to compare our prevalence rates since they are
calculated only for a three-year period of the present study, however the exceptionally
well executed study from USA estimated that there are 53 undiagnosed patients for
each celiac disease patient (5). And this is the case for a country with highly developed
health system. As visible from Figure 1, the incidence rates in our region in a 3-year
period are in a accelerated rise, as a result of a better ascertainment and availability of
diagnostics in our region. We estimate that the prevalence of celiac disease in our
region is comparable with surrounding countries.
As with many other autoimmune diseases, celiac disease is more common in
women with a female to male ratio of between 2:1 and 3:1 (9, 10). According to our
study, there is also a comparable predominance of female patients with similar ratio.
There is a speculation that some genetic loci are gender-influenced and
immunoregulation is subject to hormones, which might explain gender differences (11).
Interestingly, patients over 60 who are diagnosed with celiac disease are more
commonly male (12).
Celiac disease can be diagnosed at any age with a peak at early childhood and at
the fourth and fifth decade of life. One must bear in mind that our study observed only
adult population and we detected peak incidence in age group 36 to 45 years. However
it is important to note that peak incidence for women in our study spans toward the age
group of 26 to 35 years. The diagnosis of celiac disease in advanced age is probably a
result of a diagnostic delay, rather than a result of possible late onset of the disease.
Nevertheless there are contradictory reports with some studies in favour of diagnostic
delay and other in favor of late development (13, 14, 15).
Celiac disease along with classical symptoms of diarrhea, steatorrhoea and weight
loss may encompass a broad spectrum of other clinical manifestations especially in
adult population. These symptoms are associated with a large variety of changes in the
intestinal mucosa (16, 17). According to a survey in the pediatric population in the area
of Punjabin northern India, malnutrition was clinically apparent in 83% children (18)
and other study reported prevalence of 65% of patients with different degrees of
malnutrition. Our patients were also malnourished in around 2/3 of cases according to
the BMI value.
6. CONLUSION
Numerous studies have shown a high degree of interest in the frequency of
symptoms and signs of celiac disease, given the pathophysiological disorder that
ultimately leads to a decrease in intestinal absorption. Diarrhoea as a dominant
symptom is established in numerous studies, some of which reported diarrhea as the
first symptom in around 90% of patients (19). Nonspecific abdominal pain still persist
in about half of patients and weight loss was recorded in least one-third of patients (20).
Apparently, our patients do fit into described pattern of clinical representation with
most of them presenting with diarrhea as a first clinical symptom, with anaemia and
weight loss present in around 2/3 of patients.
There are several limitations of our study that need to be addressed. This is a
hospital-based series and there is a possible limitation of referral bias. Also, it is based
on patient records from a single hospital. Yet, our hospital is the only centre in our
region with the full diagnostic capability for diagnosing of celiac disease so almost all
patients eventually end up in our centre. Nevertheless, we allow for possibility that
small number of patients remains undetected.
At the end, as with many other countries, we feel that we in Bosnia and
Herzegovina are only uncovering the top of the iceberg when dealing with celiac
disease. The incidence in our region is demonstrating a steep rise and apparently low
prevalence in our region is merely a result of poor availability of diagnostic in previous
years. Celiac disease in adult population is more frequent than previously imagined and
should be taken into account in each patient with possible signs of intestinal disease.
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