Transcript Inflammatory Bowel Disease in Iran

Inflammatory Bowel
Disease in Iran
Inflammatory bowel disease IBD

Including Ulcerative Colitis (UC) and Crohn’s
Disease (CD), is a chronic and recurrent disease
triggered by genetic, environmental, and
immunologic factors.

UC can be histologicaly distinguished from CD
by the localized inflammation in the superficial
layer of the colonic mucosa.
Inflammatory bowel disease IBD
Considerable variation in the epidemiology of
IBD has been observed around the world, with a
wide range of both within and between
geographic regions.
IBD is reported more common in developed
countries than developing countries according
to previous articles.
With the highest incidence and prevalence
rates in North America and Europe.
Evolution in Epidemiology of IBD

As developing nations have become more
industrialized, the incidence of IBD has
increased.

Several studies have reported that the
incidence of IBD has increased markedly over
the latter part of the 20th century.
Evolution in Epidemiology of IBD

Studies have shown that individuals emigrating
from low prevalent regions (eg, Asia) to higher
prevalent countries eg, England, are at
increased risk for developing IBD, particularly
among first-generation children.

The emergence of IBD in traditionally low
prevalent regions (eg, in Hispanic and Asia)
suggests that the development of IBD may be
influenced by environmental risk factors.
Geographic Patterns

In the developing world, defining incidence
and prevalence is considerably more difficult
because many countries lack health care
systems administrative databases.

Also, care is centralized in hospitals;

thus, hospitalization records may more
accurately reflect prevalence of disease as
compared with hospitalization records from the
developed world.
Geographic Patterns

Where outpatient management of IBD is more
common.

To properly interpret the incidence or
prevalence data and evaluate time trends, a
systematic review of all population- based
studies is needed.
Time trend in IBD

Since The etiology and pathogenesis of IBD is not
fully understood.

Insight into the worldwide epidemiology of IBD is
important :

To identify Geographic patterns and time trends

To highlight the burden of IBD globally,

To determinant Possible environmental role in
IBD
Epidemiology of IBD in Iran

The objectives of our study were to conduct a
time trends patterns of IBD in Iran.

To evaluate the change in incidence .

Compare with systematic review of the
worldwide incidence and prevalence of UC and
CD ,
Prevalence Rate for UC and CD

in Europe ,the UC estimates ranged from 4.9 to
505 per 100,000,

in Asia and the Middle East, 4.9 to 168.3 per
100,000

in North America, 37.5 to 248.6 per 100,000
 The
CD estimates ranged from 0.6 to 322 per
100,000 in Europe,

0.88 to 67.9 per 100,000 in Asia and the Middle
East, and 16.7 to 318.5 per 100,000 in North
America
Epidemiology of IBD in Iran

1985- Ulcerative colitis in Iran: a review of 112
cases, by Mir-Madjlessi et al. 1973-1982 They reported the
extreme rarity of Crohn's disease in Iran.
2005- Inflammatory bowel disease in Iran: A
review of 457 cases, by Aaghazadeh , Zali, et al.
Including 401 UC, 47 CD and 9 IC

2008- Epidemiology of Inflammatory Bowel
Disease in Iran: A review of 803 cases by
Derakhshan et al. Gastroenterology and Hepatology from bed to
bench. 2008;1(1):19-24

1992-2007 Including 671 UC, 109 CD and 23 IC
Epidemiology of IBD in Iran
2009- Epidemiologic Characteristics of 500
Patients with IBD in Iran Studied from 2004
through 2007, by Vahedi et al. Arch Iranian Med
.

2012- Epidemiology of Pediatric Inflammatory
Bowel Diseases in Southern Iran, by Dehghani et
al. 2001-2007 36 IBD including 26 UC and 9 CD

2013- Epidemiological and Clinical
Characteristics of Inflammatory Bowel Disease in
Patients from Northwestern Iran, by Masnadi Shirazi et al.
Middle East Journal of Digestive Diseases, Vol.5, No.2, April 2013 2005-2007
200 IBD patients including 183
UC and 17 CD
IBD Registry and epidemiological
research in RCGLD
 IBD
Registry in
 Taleghani
Hospital, Shahid Beheshti University,
Tehran, Iran
 Private
clinic
IBD Registry and epidemiological
research in RCGLD (cont.)

During 10 years, between 1992 and 2012 we
recorded patient’s data in a questionnaire

Demographic information

Medical, familial and habitual history

Diagnosis identification

Signs and symptoms at onset and visit date

Extra-intestinal manifestations

Complications

Colonoscopy reports
IBD Registry and epidemiological
research in RCGLD (cont.)

The interview was performed face to face by trained
practitioners.

General information was retrieved from medical records of
patients by gastroenterologists.

The patients were followed up by telephone who required
proper information.

Gastroenterologists confirmed IBD in patients based on
clinical, radiological, endoscopic and pathological criteria.
IBD Registry and epidemiological
research in RCGLD (cont.)

The data base were updated through referring IBD
patients for determining any other changes such as;

Hospitalization

Drug use

Colonoscopy

Pathology

Laboratory tests

New disease
Results of IBD registry studies in RCGLD


From 1992 to 2012, 2257 patients with IBD were
confirmed in this study.
The result of the data registry system concluded
1914
343
with UC (84.8 %)
with CD (15.2 %)
Prevalence of IBD

The prevalence of UC was 5 times higher than
CD.

Similar to the fourfold higher incidence of
ulcerative colitis than Crohn's disease in
Japanese, Korean, and Chinese cohorts

According to recent studies, both diseases have
been reported with an increase in number in
eastern countries.
Male to female graph in IBD (%)
Mean age at onset
Mean age at diagnosis
Characteristics of IBD

CD was diagnosed at a younger age than UC
and IC.

The peak age of onset in this study appears to
be in the 2nd and 3rd decades of life in UC and
CD patients, consistence with findings in the
West and Asia for IBD.
Results of IBD registry studies in RCGLD


Never smoked
 93.5%
patients with UC
 90.2%
with CD
Current smokers
 6.5%
patients with UC 10.8% with CD
 Appendectomy
 4.4%
UC patients,
 14.2%
CD patients
was carried out in
Level of Education and IBD
Results of IBD registry studies in RCGLD

UC presented with
 diarrhea
(75.3%)
 hematochesia
 bloody
(73%)
diarrhea (64.8%)
 abdominal
pain (57.4%)
 weakness
(56.8%)
 tenesmus
(55.8%)
UC presentation
Results of IBD registry studies in RCGLD

CD patients complained of
 abdominal
 diarrhea
(62.3%)
 weakness
 weight
pain (72.6%)
(52.1%)
loss (55.8%)
CD presentation
Results of IBD registry studies in RCGLD


Extension of disease was evaluated with colonoscopy
procedure in UC patients as follows:

10.9% proctitis

14.3% proctosigmoiditis

13.8% left side colitis

5.9% pancolitis
Colonoscopy was performed in CD patients in which
71.8% were categorized as having ileocolitis and terminal
ileum was affected in 21.8% of patients.
Extension of disease in UC
Results of IBD registry studies in RCGLD

Major complications of UC were
 severe
bleeding (3.4%)
 dysplasia
(1.1%)
 pouchitis
(0.2%)
 intestinal
perforation (0.5%)
 toxic
mega colon (0.4%)
 stenosis
(0.9%)
Results of IBD registry studies in RCGLD

Extraintestinal manifestations were reported in

59.9% of UC patients

64.2% of CD

Musculoskeletal (26.8%) and skin (18.2%) disorders were
the most common affected sites in IBD patients.

Sclerosing cholangitis was diagnosed in 8.1% of IBD
patients
Results of IBD registry studies in RCGLD

The mean lag time between age of onset and age of
diagnosis was

8 months in UC

20 months in CD

In CD patients 25.6% had documented fistula.

Colectomy rate was 2.8% UC patients and 15.8% CD
patients .

Colorectal cancer was determined in 1% of IBD patients
(UC and CD patients).
Previous study on appendectomy and
tonsillectomy in Iranian IBD patients

2006- Appendectomy, tonsillectomy, and risk of
inflammatory bowel disease: a case control study in Iran.
Int J Colorectal Dis (2006) 21: 155–159.

382 UC and 46 CD were studied.

382 controls for UC and 184 controls for CD were enrolled.

Appendectomy is protective in UC, but a risk factor in CD
among Iranian population.

Tonsillectomy was not associated with either UC or CD disease.
UC, but not CD, is a disease of non- smokers.

The inverse association between ulcerative colitis and OCP or
NSAID in the Iranian population is noted.
Results of IBD registry studies in RCGLD

Familial history of IBD was presented in
 14.2%
UC patients, of whom 57.9% had a positive
family history in first-degree and 42.1% in seconddegree relatives.
 IBD
was affected 15.8% cases of CD patients,
identifying 57.1% in first- and 42.9% in second-degree
relatives.
IBD Genetics research in RCGLD


2007- The frequency of C3435T MDR1 gene
polymorphism in Iranian patients with ulcerative colitis. Int
J Colorectal Dis. 2007 Sep; 22(9):999-1003.

300 UC and 300 controls

C3435T polymorphism of the MDR1 gene has an association with
UC in Iranian population as in western countries.
2008- Frequency of three common mutations of
CARD15/NOD2 gene in Iranian IBD patients. Indian
journal of Gastroenterology, 2008, Vol. 27, No 1: 9-11.

100 UC, 40 CD and 100 controls

R702W mutation of CARD15/NOD2 gene was more frequent in
CD patients than controls
IBD Genetics research in RCGLD (cont.)

Association of vitamin D receptor gene
polymorphisms in Iranian patients with
inflammatory bowel disease. J Gastroenterol.
Hepatol. 2008 Dec;23(12):1816-22.
 150
A
UC, 80 CD and 150 controls
probable association of the Fok I polymorphism in
VDR receptor gene and Crohn's susceptibility in
Iranian population was observed.
IBD Genetics research in RCGLD (cont.)

2011- NOD2 exonic variations in Iranian Crohn's
disease patients. Int J Colorectal Dis (2011)
26:775–781.
 90
CD and 120 controls
 21
sequence variations were identified among all
exonic regions of the NOD2 gene, of which eight had
an allele frequency of more than 5%.
 Eight
new mutations (one in exon 2 and seven in exon
4) were observed.
IBD Genetics research in RCGLD (cont.)

The three main variants (R702W, G908R, and 1007fs)
showed allele frequencies of 13.3%, 2.2%, and 1.7%,
respectively.

Three new variations (P371T, A794P, and Q908H) and
R702W mutation were significantly more frequent in Crohn's
disease patients compared to controls.

Eight novel mutations were identified in the NOD2 exons,
but the pathophysiological importance of these variants
remains unclear.

Iranian patients with their different genetic reservoirs may
demonstrate some novel characteristics for disease
susceptibility.
Genetic Factors

Among the 100 IBD genes and loci defined,

only nucleotide binding oligomerization domain
protein 2 (NOD2) (5% penetrance or 20-fold risk
in mutation homozygotes, has a meaningful
contribution to CD risk alone.


All remaining genes and loci contribute
modestly to IBD risks, However, the exact
relationship between genetic susceptibility and
the role of the environment in the pathogenesis
of IBD still largely remains a mystery
Time Trends of IBD types In Iran
Changing Environment


The clinical picture of a patient with IBD results
from a complex interaction of
genetic,

environmental,

developmental and disease course factors,

such as the patient’s age, nutritional status and
presence of co-morbidities.
Genetic Factors

Genetic susceptibility plays a key role in IBD
development.

8- to 10-fold greater risk of IBD among relatives of
ulcerative colitis ,and Crohn’s disease.

To be involved in the ethiology of IBD,

Are associated with immune functions,

Mucosal transport functions, or bacterial
recognition.
Environmental Factors


Given the patho-physiologic complexity inherent
in IBD,
it is unlikely that genetics alone will provide

sufficient information for time trend in IBD.

Rates of appendectomies have decreased in
developed countries, whereas the incidence of
UC has remained constant.
Health Care Improvement

The rising incidence of IBD during the 20th
century may be explained by environmental
exposures that result from increasing

urbanization;

For example, IBD occurs more commonly in
urban versus rural regions.
Environmental Risk Factors

Individuals raised in urban areas are exposed to
considerably different environmental risk factors
than those living outside these regions.,

microbial exposures,

sanitation,

occupations,

Diet, lifestyle behaviors, medications, and

pollution exposures, which have all been
implicated as potential environmental risk
factors for IBD.
Access to Medical Services
however, this increase could be due to.
Increased awareness of IBD by physicians
and the public,
Advancements in diagnostic methods for IBD
Such as access to medical services,
Access to colonoscopies,
Withy greater differentiation of CD from UC.
Environmental Factors

Smoking cannot explain worldwide increases in
CD; as the incidence of CD is low in several
populations of heavy smokers (Asia, Africa) and
high in some populations of mild smokers.

Dysbiosis, Microbiota etc.,

However, these parameters cannot account for
all variations in IBD incidence and prevalence;
Where Do we Stand Now?
The Global Prevalence

The incidence of IBD is increasing or stable in
virtually every region of the world.

Since 1980, 56% of CD and 29% of UC studies
have shown a statistically significant increasing
incidence.

Because mortality in IBD is low, and the disease is
most often diagnosed in the Young,

These findings suggest that the global
prevalence of IBD will continue to increase
substantially.
Treatment Target IBD are Evolving

Increasing use of immunomodulators, such as
thiopurines,

the introduction of infliximab in 1998

From Clinical Remission to Mucosal healing

Deep Remission.

Has changed the course of disease in many
patients.
Future Direction

To advance our understanding of the

key determinants of IBD in the developed and
developing world,

future population-based studies should focus on

Reporting incidence and/or prevalence of IBD
stratified by gene-environment-phenotype
interactions.
Conclusions (1)

As we move forward into the next two to three

decades of IBD, we will face a series of

challenges. We must:

1. Identify disease targets and patients who will

benefit the most by certain classes of drugs.

2. Design treatment strategies that will decrease

loss of response to therapy.
Conclusions (2)

3. Identify individual risk factors for aggressive

disease and treat those patients accordingly to

change the natural history of disease.

4. Develop strategies that will minimize

neoplastic and infectious risks of our targeted

drug therapies.
Future Direction of IBD