This study analyzed the frequency and relationship of extraintestinal manifestations (EIMs) with disease phenotype in 1,652 patients with inflammatory bowel disease (IBD), including 1,146 with ulcerative colitis (UC), 303 with Crohn's disease (CD), and 203 with intestinal tuberculosis (ITB) at a hospital in India between 2005-2012. The frequency of any EIM was 33.2% in UC patients, 38.3% in CD patients, and 14.3% in ITB patients. Peripheral arthropathy, erythema nodosum, and aphthous stomatitis were more common in CD than UC. Any EIM and multiple EIMs were more frequent in

1. ORIGINAL ARTICLE
Extraintestinal manifestations of inflammatory bowel disease
and intestinal tuberculosis: Frequency and relation with disease
phenotype
Bikramjit Singh & Saurabh Kedia & Gauree Konijeti & Venigalla Pratap Mouli &
Rajan Dhingra & Lalit Kurrey & Saurabh Srivastava & Rajesh Pradhan &
Govind Makharia & Vineet Ahuja
Received: 28 July 2014 /Accepted: 5 January 2015 /Published online: 7 February 2015
# Indian Society of Gastroenterology 2015
Abstract
Background Extraintestinal manifestations (EIMs) in inflam-
matory bowel disease (IBD) including ulcerative colitis (UC)
and Crohn’s disease (CD), as well as intestinal tuberculosis
(ITB) from Asia, are underreported. We, therefore, describe
the prevalence of EIMs in Indian IBD and ITB patients and
study their relationship with disease extent and severity in
IBD.
Methods This retrospective single-center study included all
IBD and ITB patients evaluated from January 2005 to
July 2012. Disease profile and frequencies of arthropathies
(peripheral and central) and ocular (episcleritis, iritis/uve-
itis), oral (aphthous stomatitis), skin (erythema nodosum,
pyoderma gangrenosum, psoriasis), hepatobiliary (primary
sclerosing cholangitis), and thromboembolic manifestations
were analyzed.
Results Of 1,652 patients (1146 UC, 303 CD, 203 ITB), fre-
quency of any EIM was 33.2 %, 38.3 %, and 14.3 % in UC,
CD, and ITB patients, respectively. Thromboembolism was
more common among UC patients with pancolitis than
proctitis (p<0.001) and left-sided colitis (p=0.02). Primary
sclerosing cholangitis was seen in 0.4 % UC patients.
Steroid-dependent UC patients had higher frequency of any
EIM, peripheral arthropathy, or thromboembolism than pa-
tients with no or infrequent steroid requirement (p<0.05). Pe-
ripheral arthropathy (p=0.02), erythema nodosum (p=0.01),
and aphthous stomatitis (p=0.004) were more common with
CD than with UC patients. Patients with colonic CD had
higher frequency of peripheral arthropathy, any EIM, and mul-
tiple EIMs than ileal or ileocolonic disease (p<0.05). Relative
to ITB, CD patients had higher frequencies of peripheral ar-
thropathy (p<0.001), aphthous stomatitis (p=0.01), any EIM
(p<0.001), and multiple EIMs (p<0.001).
Conclusions In Indian IBD and ITB patients, EIMs appear to
be related to disease severity in UC and disease location in CD
and are significantly more common in CD than in ITB. Over-
all prevalence of EIMs in these patients is similar to that of the
West.
Keywords Extraintestinal manifestations . Inflammatory
bowel diseases . Intestinal tuberculosis
Introduction
The inflammatory bowel diseases (IBDs) are premised a con-
sequence of genetic, environmental, and immunological inter-
actions between host and commensal flora of the intestine [1].
Extraintestinal manifestations (EIMs) seen in ulcerative colitis
(UC) and Crohn’s disease (CD) can be either immune-
mediated or occur as a result of severe intestinal inflammation
or extensive resection [2]. Typically, EIMs in UC and CD
include arthropathies, mucocutaneous and ophthalmological
manifestations, and conditions affecting the hepatobiliary sys-
tem. There are several published studies on the prevalence of
Electronic supplementary material The online version of this article
(doi:10.1007/s12664-015-0538-7) contains supplementary material,
which is available to authorized users.
B. Singh :S. Kedia :V. P. Mouli :R. Dhingra :L. Kurrey :
S. Srivastava :R. Pradhan :G. Makharia :V. Ahuja (*)
Department of Gastroenterology and Human Nutrition, All India
Institute of Medical Sciences, Ansari Nagar, New Delhi 110 029,
India
e-mail: vins_ahuja@hotmail.com
G. Konijeti
Gastrointestinal Unit, Massachusetts General Hospital, Boston, USA
Indian J Gastroenterol (January–February 2015) 34(1):43–50
DOI 10.1007/s12664-015-0538-7

2. EIMs in IBD patients from the West [3–5]. However, reports
on the same from Asian countries are scarce [6]. This might
reflect the previously low prevalence of IBD in this region,
although recent studies now report increasing incidence of
both disorders [7, 8]. Secondly, prior studies included smaller
numbers and heterogeneous patient sample populations, lim-
iting accurate assessment [9, 10]. Further, detailed descrip-
tions of the relationship between EIMs and disease extent
and severity in this region are lacking. Therefore, the overall
burden and impact of EIMs in IBD patients in Asian countries
remains ambiguous.
Patients with intestinal tuberculosis (ITB) have also been
reported to have EIMs, although the prevalence of EIMs
in ITB has not been systematically investigated. Crohn’s
disease and ITB are similar granulomatous disorders with
different etiologies. The ability of TB to affect multiple
extraintestinal sites, along with associated immunological
phenomena, accounts for the involvement of joints, skin,
eye, and liver in these patients in endemic regions. These
disorders include immune-mediated reactive polyarthritis
(Poncet’s disease), erythema nodosum, and uveitis. There
are several reports examining clinical, endoscopic, and
histological differences between ITB and CD, but data
including prevalence rates of EIMs in patients with ITB
and CD are scarce, incongruous, and include small
numbers [11–13].
The All India Institute of Medical Sciences (AIIMS)
in New Delhi is a tertiary care center where patients
with IBD are referred to from all parts of India. Our
Inflammatory Bowel Disease Clinic (IBDC) has main-
tained records on patients with UC, CD, and ITB since
2005. The present study was therefore designed to de-
scribe and compare the prevalence of EIMs in Indian
patients with IBD and ITB and to study the relationship
of EIMs with disease extent and severity.
Methods
Patient population
All patients with UC, CD, and ITB in attendance at the
AIIMS, IBDC from January 2005 to July 2012 were included
in the study. Patients with IBD or ITB who first came to
us in July 2012 or beyond were not included because of
limited follow up data. Many patients with a diagnostic
dilemma between ITB and CD were given a therapeutic
trial of antitubercular therapy (ATT) for 6 months, and the
final diagnosis was based on clinical, radiographic, and
endoscopic response to ATT. Therefore, a minimum follow
up of 6 months was required before these patients could
be included.
Study design
Demographic and clinical data for all patients with UC,
CD, and ITB were retrieved from medical records in
this retrospective study. Our medical records comprised
a paper file system where each patient was assigned an
IBD number, mentioned on the face of the file, along
with patient name, age, sex, and diagnosis, and the lat-
ter was also mentioned on the first page of the file.
Each file contained all dated information concerning
the patient’s disease, including a detailed history, medi-
cal exam, relevant test findings, and follow up symptom
assessment. A team of physicians maintained the files,
and the parameters used for assessment were consistent
between physicians and throughout the 7-year study pe-
riod. In the absence of flares, patients were asked to
follow up every 6 months. Complete confidentiality
was ensured during the review process for the purpose
of the study. Data was compiled on an Excel sheet and
statistically analyzed. We specifically looked at the du-
ration of symptoms at presentation, disease extent ac-
cording to Montreal classification [14], disease behavior
in patients with ITB and CD [14], and frequency of
various EIMs. The EIMs examined included musculo-
skeletal (peripheral joint pain, inflammatory backache,
ankylosing spondylitis), dermatological (pyoderma
gangrenosum, erythema nodosum, psoriasis), ocular
(episcleritis, uveitis/iritis), hepatobiliary [primary scle-
rosing cholangitis (PSC)], and thromboembolic manifes-
tations and were assessed at the time of initial presen-
tation as well as during follow up visits. Patients who
developed rheumatologic, dermatologic, or ocular com-
plications were referred to an appropriate specialist
(rheumatologist/dermatologist/ophthalmologist). Final di-
agnosis and treatment of these complications was done
as per the advice of concerned specialist. Institutional
ethics committee approved the study protocol.
Definitions
Diagnosis of ulcerative colitis
The patients were diagnosed as UC on the basis of the Euro-
pean Crohn’s and Colitis Organization (ECCO) guidelines,
employing a combination of clinical, endoscopic, and histo-
logical features [15].
Diagnosis of Crohn’s disease
The patients were diagnosed as CD on the basis of ECCO
guidelines, using a combination of clinical, endoscopic, and
histological features [16].
44 Indian J Gastroenterol (January–February 2015) 34(1):43–50

3. Diagnosis of intestinal tuberculosis
The diagnosis of ITB was made on the basis of characteristic
clinical features (abdominal pain, constitutional symptoms,
and intestinal obstruction), endoscopic features (ileocecal area
involvement, ulcerations, nodularity, and strictures), histolo-
gical features (presence of granulomas) and microbiological
tests (presence of acid-fast bacilli on smear examination or
culture), and response to ATT (Paustian’s criteria with Logan’s
modification) [17, 18].
Indeterminate cases
In patients who did not fulfill the gold standards for CD or
ITB, empirical ATT was given. A diagnosis of ITB was made
if the patient showed clinical and endoscopic response to ATT
within 6 months. A diagnosis of Crohn’s disease was made if
the patient showed no improvement, or his condition wors-
ened, or worsened after initial improvement with standard
ATT and subsequently showed clinical and/or endoscopic re-
sponse to oral steroids [19, 20].
Disease extent and course in ulcerative colitis
Disease extent was classified according to the Montreal clas-
sification. Disease course was divided into three types based
on the frequency of steroid use at most recent follow up
(which would be an indirect marker of disease activity)
(Table 1).
Disease location and behavior in Crohn’s disease
Both location and behavior were classified according to the
Montreal classification (Table 1).
Statistical analysis
Continuous variables were expressed as mean±standard devia-
tion or median (interquartile range) depending on normal or
non-normal distribution. Categorical variables were expressed
as percentages. The comparison between categorical variables
was done using chi-square test or Fisher’s exact test as appro-
priate. Continuous variables were compared with Student t test
or Mann-Whitney U test as relevant. Comparisons for EIMs
were also done with respect to disease extent of UC and CD,
disease severity of UC, and disease behavior of CD. SPPS soft-
ware version 17.0 was used for analysis. All analyses were two-
sided and p-value <0.05 was taken as statistically significant.
Results
Baseline clinical and demographic characteristics
A total of 1,449 patients with IBD (1146 UC and 303 CD) and
203 patients with ITB were included. There were no signifi-
cant differences in age or gender distribution between patients
with UC, ITB, and CD (Supplementary Table 1).
More than half (55.8 %) UC patients had left-sided colitis,
30.7 % had pancolitis, and 13.5 % had proctitis alone. Almost
7 % of UC patients were steroid-dependent, and 36.8 % pa-
tients never required steroids (Supplementary Table 1). Colon-
ic (35.3 %) and ileocolonic (41.3 %) were the most common
disease locations in CD patients. Inflammatory (50.2 %) and
stricturing (43.9 %) phenotypes were the most frequent dis-
ease behaviors (Supplementary Table 1).
Extraintestinal features in patients with inflammatory bowel
disease and intestinal tuberculosis
The frequencies of EIMs which included any one of joint, eye,
skin, hepatobiliary, or thromboembolic manifestations (any
Table 1 Definitions of disease extent and course in patients with ulcerative colitis and disease location and behavior in patients with Crohn’s disease
Disease extent and course in ulcerative colitis Disease location and behavior in Crohn’s disease
Extent Location
• Proctitis (E1) • Involvement limited to the rectum • L1 • Ileal
• Left-sided colitis (E2) • Involvement limited to a proportion of the colorectum distal
to the splenic flexure
• L2 • Colonic
• Pancolitis (E3) • Involvement extends proximal to the splenic flexure • L3 • Ileocolonic
• L4 • Isolated upper gut disease
Course Behavior
• Type 1 • Never required steroids • B1 • Non-stricturing, non-penetrating
• Type 2 • Required steroids infrequently (<2 times in a year) • B2 • Stricturing
• Type 3 • Steroid dependent • B3 • Penetrating
• P • Perianal disease modifier
Indian J Gastroenterol (January–February 2015) 34(1):43–50 45

4. EIM), were 33.2 %, 38.3 %, and 14.3 % in patients with UC,
CD, and ITB, respectively (Tables 2 and 3).
The frequency of peripheral arthropathy (26.1 % vs.
19.8 %, p=0.02), erythema nodosum (1.3 % vs. 0.2 %, p=
0.01), and aphthous stomatitis (8.6 % vs. 4.5 %, p=0.004)
were significantly higher in patients with CD than UC
(Table 2). There was no difference in the frequency of
the other EIMs. PSC was seen in 0.4 % patients with
UC. The frequencies of any EIM (38.3 % vs. 33.2 %,
p=0.09) and multiple EIMs (6.9 % vs. 4.7 %, p=0.14)
were slightly higher in patients with CD than in those
with UC.
The frequencies of any EIM (38.3 % vs. 14.3 %, p<0.001),
multiple EIMs (6.9 % vs. 1.5 %, p<0.001), peripheral arthrop-
athy (26.1 % vs. 7.9 %, p<0.001), and aphthous stomatitis
(8.6 % vs. 3 %, p=0.01) were significantly higher in CD than
in ITB patients (Table 3). Although the prevalence of all other
EIMs was also higher in CD than in ITB, the difference was
not significant because of lower frequencies of these EIMs.
No patient with either CD or ITB had PSC.
Frequency of extraintestinal manifestations with respect
to disease severity and disease extent in ulcerative colitis
The frequencies of EIMs, except for thromboembolic mani-
festations and PSC, were not significantly different with re-
spect to disease extent in patients with UC (Supplementary
Table 2). Thromboembolic manifestation was significantly
more common in patients with pancolitis than in those with
proctitis (3.1 % vs. 0 %, p<0.001) and left-sided colitis (3.1 %
vs. 0.3 %, p=0.02). All patients with PSC had pancolitis.
Steroid-dependent UC patients had significantly higher fre-
quency of any EIM (40.5 % vs. 28.9 %, p=0.04), thromboem-
bolism (3.8 % vs. 0.2 %, p=0.01), and peripheral arthropathy
(30.4 % vs. 17.5 %, p=0.01) than patients with no steroid re-
quirement (Fig. 1). Although these EIMs in steroid-dependent
patients were more common than those in patients with less
frequent steroid requirement, only the peripheral arthropathy
reached statistical significance. There was no difference in the
frequency of other EIMs between the three subgroups.
Frequency of extraintestinal manifestations with respect
to disease location and disease behavior in Crohn’s disease
Patients with colonic (L2) CD had the highest frequency of
peripheral arthropathy [39.3 % vs. 16.1 % (L1) and 20.8 %
(L3)], any EIM [(52.3 % vs. 27.9 % (L1) and 33.6 % (L3)],
and multiple EIMs [(11.2 % vs. 6.6 % (L1) and 4 % (L3)] than
ileal (L1) or ileocolonic (L3) disease (p<0.05 for all, Fig. 2).
Although the frequencies of other EIMs (except thromboem-
bolism) were highest in patients with colonic disease, the dif-
ference with respect to ileal and ileocolonic disease was not
significant (Supplementary Table 3).
Overall, any one EIM was significantly more common in
inflammatory CD than in stricturing (46.1 % vs. 32.3 %, p=
0.02) and penetrating disease (46.1 % vs. 16.7 %, p=0.02)
(Supplementary Table 3).
Discussion
The present study describes the prevalence of EIMs in
Indian patients as 33.2 % in UC, 38.3 % in CD, and
Table 2 Comparison of
frequency of extraintestinal
manifestations in ulcerative colitis
and Crohn’s disease
UC ulcerative colitis, CD Crohn’s
disease, PSC primary sclerosing
cholangitis, EIM extraintestinal
manifestations
UC (n=1146) CD (n=303) p-value Odds ratio
N (%) N (%)
Peripheral arthropathy 227 (19.8) 79 (26.1) 0.02 1.4 (1.1–1.9)
Central arthralgia
Ankylosing spondylitis 25 (2.2) 10 (3.3) 0.26 1.5 (0.8–3.2)
Inflammatory backache 157 (13.7) 32 (10.6) 0.15 0.7 (0.5–1.1)
Dermatological
Pyoderma gangrenosum 8 (0.7) 2 (0.7) 1 0.9 (0.2–4.5)
Erythema nodosum 2 (0.2) 4 (1.3) 0.02 7.6 (1.4–41.9)
Psoriasis 4 (0.3) 3 (1) 0.16 2.8 (0.6–12.8)
Aphthous stomatitis 51 (4.5) 26 (8.6) 0.004 2 (1.2–3.3)
Ocular
Episcleritis 10 (0.9) 4 (1.3) 0.51 1.5 (0.5–4.9)
Uveitis 16 (1.4) 2 (0.7) 0.39 0.5 (0.1–2.1)
PSC 5 (0.4) 0 0.59 0.0?
Thromboembolic events 13 (1.1) 6 (2) 0.25 1.8 (0.7–4.7)
Any EIM 380 (33.2) 116 (38.3) 0.09 1.2 (0.9–1.6)
Multiple EIM 54 (4.7) 21 (6.9) 0.14 1.5 (0.9–2.5)
46 Indian J Gastroenterol (January–February 2015) 34(1):43–50

5. 14.3 % in ITB. The prevalence of EIMs was significantly
higher in patients with CD as compared to those with ITB.
Likewise, the prevalence of multiple EIMs was highest
among patients with CD (6.9 %), followed by UC (4.7 %)
and ITB (1.5 %).
The prevalence of EIMs in UC and CD in Western studies
[21, 22] has varied from 36 % to 51.5 % and 24 % to 42.2 %,
respectively. The prevalence of multiple EIMs in CD has been
reported as 6 % [5]. The overall frequencies of EIMs in our
Indian cohort matched with those documented in the Western
literature. The prevalence of EIMs in our population was sim-
ilar to that described in other studies from India [9, 10, 23, 24]
and Iran [6] but was higher compared to China [25], Korea
[26], Thailand [27], and Puerto Rico [28].
Peripheral arthropathy was the most common EIM in both
our UC and CD patients. However, it was significantly more
prevalent in patients with CD than in those with UC. Because
of the nature of patient records, we could not subclassify
peripheral arthropathy into arthralgia and arthritis or into type
1 and type 2 arthritis. The prevalence of peripheral arthropathy
in the present study was similar to that previously reported in
the Western literature [5, 21]. However, the prevalence of
peripheral arthropathy was higher than that reported in earlier
Indian [9, 10] and other Asian studies (both Western and
South Eastern Asia) [6, 25, 26]. This could be due to differ-
ences in study design, definitions of peripheral arthralgia, and
inclusion criteria for these studies.
The prevalence of ankylosing spondylitis (AS) in the pres-
ent study is similar to previously published reports in the
Western [5] and Asian literature [6]. Similar to other studies
[3, 6, 21], we did not observe a significant difference in the
prevalence of AS between CD and UC.
Although pyoderma gangrenosum has been more com-
monly reported in UC [21], we found similar proportions in
both UC and CD. The reported prevalence rates vary from
0.5 % to 5 % for UC [4, 29] and 0.6 % to 1.2 % for CD
Table 3 Comparison of
frequency of extraintestinal
manifestations in Crohn’s disease
and intestinal tuberculosis
CD Crohn’s disease, ITB
intestinal tuberculosis, PSC
primary sclerosing cholangitis,
EIM extraintestinal
manifestations
CD (n=303) ITB (n=203) p-value Odds ratio
N (%) N (%)
Peripheral arthropathy 79 (26.1) 16 (7.9) <0.001 4.1 (2.3–7.3)
Central arthralgia
Ankylosing spondylitis 10 (3.3) 1 (0.5) 0.057 6.9 (0.9–54.2)
Inflammatory backache 32 (10.6) 13 (6.4) 0.11 1.7 (0.9–3.3)
Dermatological
Pyoderma gangrenosum 2 (0.7) 0 0.52 2.7 (0.3–24.3)
Erythema nodosum 4 (1.3) 1 (0.5) 0.65
Psoriasis 3 (1) 0 0.21
Aphthous stomatitis 26 (8.6) 6 (3) 0.01 3.1 (1.2–7.6)
Ocular
Episcleritis 4 (1.3) 1 (0.5) 0.65 2.7 (0.3–2 4.3)
Uveitis 2 (0.7) 1 (0.5) 1.0 1.3 (0.1–14.9)
PSC 0 0
Thromboembolic 6 (2) 0 0.09 1.8 (0.7–4.7)
Any EIM 116 (38.3) 29 (14.3) <0.001 3.7 (2.4–5.9)
Multiple EIM 21 (6.9) 3 (1.5) <0.001 4.9 (1.5–16.9)
17.5*
0.2*
28.9*
4
20*
1.4
35
4.8
30.4
3.8
40.5
7.6
0
5
10
15
20
25
30
35
40
45
Peripheral
arthropathy
Thromboembolism Any EIM Multiple EIMs
FrequenciesofEIMs(%)
No steroid
requirement
Infrequent
steroid
requirement
Steroid
dependent
Fig. 1 Comparison of
extraintestinal manifestations
with respect to disease course in
patients with ulcerative colitis
Indian J Gastroenterol (January–February 2015) 34(1):43–50 47

6. [30]. Frequency of erythema nodosum in our study was higher
in CD (1.3 %) than in UC (0.2 %). However, the overall prev-
alence of dermatologic manifestations was lower in our patients
compared to previous studies in the Western and Asian litera-
ture. The reported prevalence rates of erythema nodosum for
UC vary from 0.9 % to 4 % [22, 31] and for CD vary from
1.9 % to 5.6 % [21, 30]. Psoriasis has also been reported as
more common in IBD patients than in the general population.
The prevalence of psoriasis in IBD in a Turkish study [32] was
3.1 %. In the present study, psoriasis was seen in 0.5 % of IBD
patients. Reported prevalence of aphthous stomatitis varies
from 1.3 % to 13 % in the literature [6, 9, 21]. In our study,
aphthous stomatitis was more common in patients with CD
than in those with UC (8.6 % vs. 4.5 %, p=0.004).
Ocular manifestations have been reported in 0.3 % to 5 % of
all IBD patients [33]. Patients with colonic involvement are
affected more frequently [34], as too are patients with other
EIMs, particularly peripheral arthritis. In the present study, oc-
ular involvement was seen in 2 .3 % and 2 % patients with UC
and CD, respectively. As reported previously as well, in the
present study, the prevalence of ocular involvement was
highest in patients with colonic CD (although the difference
was not significant because of lower frequency) and more fre-
quent in patients with peripheral arthropathy (4.9 % vs. 1.5 %).
PSC has been strongly associated with IBD, particularly
UC, and the reported prevalence of PSC in UC ranges from
2.4 % to 7.4 % in the Western literature [35]. The prevalence
of PSC in patients with UC in Asian reports varies from 1.3 %
to 3.9 % [6, 9]. The prevalence of PSC varies, owing to dif-
ferences in definition or methods of diagnosis. We included
patients who had ERCP or MRCP evidence of PSC, in addi-
tion to biochemical abnormalities. PSC was seen in only
0.4 % patients of UC and it was not seen in any patient with
CD. The reason for such low prevalence of PSC in our study
might be due to the overall low prevalence rate of autoimmune
liver disease in Indian patients. Autoimmune liver diseases
accounted for only 1 .7 % to 5.7 % of all chronic liver disease
in published reports from India [36, 37]. Among them, PSC
accounted for only 5.2 % of all autoimmune liver disease and
0.2 % of all chronic liver disease.
There is a threefold increased risk of venous thromboem-
bolism (VTE) in patients with IBD [38]. There are multiple
factors that account for this, including disease activity, immo-
bility, and corticosteroid use [39]. However, there are very few
studies which have reported the prevalence of VTE in IBD,
which varies from 0.9 % to 2 % [9]. We too observed a VTE
prevalence of 1.1 % and 2 % in patients with UC and CD,
respectively.
Correlation between the prevalence of EIMs and disease
extent in UC has varied in published reports because some
studies have assessed this in the context of disease extent
while others have not. In the present study, except for throm-
boembolism, there was no effect of disease extent on the prev-
alence of EIMs. Thromboembolism was most common in
patients with UC pancolitis. We classified the disease severity
on the basis of steroid use, into steroid-dependent, infrequent
steroid requirement (<2/year), or no steroid requirement. The
prevalence of any EIM, multiple EIMs, peripheral arthropa-
thy, and thromboembolism was significantly higher in steroid-
dependent patients. Previous studies also have found a higher
prevalence of EIMs with increased disease severity, although
the definition of disease severity has varied among them [40].
Studies have also correlated the prevalence of EIMs with
disease location in CD patients, with the highest prevalence
being reported in patients with colonic disease [21]. Similarly
in the present study, the prevalence of peripheral arthropathy,
any EIM, and multiple EIMs was highest in patients with
colonic CD. The frequency of other EIMs (except thrombo-
embolism) was also highest in patients with colonic CD, al-
though the difference with respect to ileal and ileocolonic
disease was not significant. We also found an increased prev-
alence of any EIM in CD patients with inflammatory disease
behavior. This may be due to the higher proportions of colonic
disease in our CD patients with inflammatory behavior
[(44.3 % vs. 26 % (B2) and 33 % (B3)].
Although there are few studies which have compared the
overall prevalence of EIM between patients with CD (10.9 %
to 61.5 %) and those with ITB (1.8 % to 23.1 %) [12, 13],
there is only one study which has compared the individual
EIMs between the two diseases [12]. However, this was a
16.1*
27.9*
6.6*
39.3
52.3
11.2
20.8*
33.6*
4 *
0
10
20
30
40
50
60
Peripheral arthropathy Any EIM Multiple EIMs
FrequenciesofEIMs(%)
Ileal
Colonic
Ileocolonic
Fig. 2 Comparison of
extraintestinal manifestations
with respect to disease location in
patients with Crohn’s disease
48 Indian J Gastroenterol (January–February 2015) 34(1):43–50

7. small study with only 26 patients in each group. However, as
seen in this study, we too noticed that EIMs were more com-
mon in CD compared to ITB (38.3 % vs. 14.3 %, p<0.001).
Among patients with ITB, peripheral arthropathy was the
most common EIM (7.9 %), followed by aphthous ulcers
(3 %). The following EIMs were seen in only 0.5 % of
patients: erythema nodosum, episcleritis, uveitis, and AS.
We did not observe pyoderma gangrenosum, PSC, or throm-
boembolism in any patient with ITB. Thus, although we did
observe the reported immune-mediated EIMs in patients with
ITB, they were at a much lower frequency compared to CD.
This is the largest single-center study from Asia, which has
systematically reported the prevalence of EIMs in patients
with IBD as well as ITB. It is also the only study from Asia
that has correlated EIMs with disease extent and severity in
UC patients and disease location in patients with CD and
compared EIMs between CD and ITB in a large number of
patients.
The limitations of our study include a retrospective design
with the data being extracted from medical records. Therefore,
we could not correlate the prevalence of EIM with disease du-
ration. However, the median duration of symptoms at first visit
was 28 and 42 months in patients with UC and CD, respectively,
and this was significantly longer in patients with EIM than in
those without (36 vs. 27.6 months, p=0.037). We also did not
look for less frequent EIMs including renal, pulmonary, and
neurological involvement.
We may thus draw the following conclusions: first, the
prevalence of EIMs in Indian patients with IBD is similar to
that in the West and in some Asian countries, although there
are differences in individual EIMs; second, EIMs are related
to disease severity in UC, and they were more common in
patients with steroid-dependent UC; third, EIMs were more
common in patients with colonic CD; and last, EIMs were
significantly more common in patients with CD than in those
with ITB.
Conflict of interest BS, SK, GK, VPM, RD, LK, SS, RP, GM, and VA
confirm that they have no conflicts of interest to declare.
Ethics statement The study was performed in a manner to conform
with the Helsinki Declaration of 1975, as revised in 2000 and 2008
concerning Human and Animal Rights, and the authors followed the
policy concerning informed consent as shown on Springer.com.
Financial support The study did not receive any financial support.
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