ORIGINAL ARTICLE

Inflammatory bowel disease is associated

with an increased risk of inflammatory
skin diseases: A population-based
cross-sectional study
Miri Kim, MD, PhD,a Kwang Hyun Choi, MD,b Se Won Hwang, MD,a Young Bok Lee, MD, PhD,a
Hyun Jeong Park, MD, PhD,a and Jung Min Bae, MD, PhDa
Seoul, Korea

Background: Inflammatory bowel disease (IBD) is a chronic disease of the gastrointestinal tract attributed
to aberrant activity of the immune system. Increasing evidence suggests that patients with IBD are at an
increased risk of inflammatory skin diseases (ISDs).

Objective: We sought to clarify the association between IBD and ISDs using a nationwide health claims
database maintained in Korea.

Methods: We interrogated Korean health claim database data from 2009 to 2013. We enrolled all patients
with IBD, and age- and sex-matched control subjects, and evaluated the risks of ISDs, including psoriasis,
rosacea, and atopic dermatitis, and the risks of autoimmune skin diseases, including vitiligo and alopecia
areata. We used multivariable logistic regression to this end.

Results: ISDs including rosacea, psoriasis, and atopic dermatitis were significantly associated with IBD,
whereas the associations between IBD and autoimmune skin diseases including vitiligo and alopecia areata
were less marked or nonexistent. Ulcerative colitis and Crohns disease were both associated with ISDs.

Limitations: We were unable to distinguish phenotypes and severities of skin diseases.

Conclusion: IBD was significantly associated with ISDs, but less so or not at all with autoimmune skin
diseases. ( J Am Acad Dermatol http://dx.doi.org/10.1016/j.jaad.2016.08.022.)

Key words: atopic dermatitis; epidemiology; inflammatory bowel disease; psoriasis; rosacea.

I nflammatory bowel disease (IBD) is a chronic
inflammatory condition of the gastrointestinal
tract caused by an aberrant immune response.
The 2 principal forms of IBD are Crohns disease
(CD) (which can affect any part of the gastrointestinal
tract) and ulcerative colitis (UC) (which affects
mainly the colon and rectum).1 Although the path-
ophysiology of IBD is not fully understood, it is
thought that complex interactions between a genetic
predisposition to disease susceptibility and many
exogenous factors alter immune function, triggering
chronic intestinal inflammation.2
Emerging epidemiologic evidence suggests that
IBD is associated with various inflammatory skin
diseases (ISDs) including psoriasis, rosacea, and
atopic dermatitis (AD). Psoriasis was associated

From the Department of Dermatology, College of Medicine, The
Catholic University of Korea,a and Veterans Health Service
Medical Center.b
Drs Kim and Choi contributed equally to this work.
Supported by a Veterans Health Service Medical Center (VHSMC)
Research Grant from the Government of the Republic of Korea
(no. VHSMC 16010).
Conflicts of interest: None declared.
Accepted for publication August 10, 2016.
Reprint requests: Jung Min Bae, MD, PhD, Department of Dermatology,
St Vincents Hospital College of Medicine, The Catholic University of
Korea, 93 Ji-dong, Paldal-gu, Suwon 440-060, Korea. E-mail:
jminbae@gmail.com. Or Hyun Jeong Park, MD, PhD, Department
of Dermatology, Yeouido St. Marys Hospital, College of Medicine,
The Catholic University of Korea, 10, 63-ro, Yeongdeungpo-gu,
Seoul, 150-713 Korea. E-mail: hjpark@catholic.ac.kr.
Published online October 25, 2016.
0190-9622/$36.00
2016 by the American Academy of Dermatology, Inc.
http://dx.doi.org/10.1016/j.jaad.2016.08.022

1
2 Kim et al J AM ACAD DERMATOL
n 2016

with a significantly increased risk of both CD (odds of analysis, patients with concurrent skin diseases
ratio [OR] 2.49) and UC (OR 1.64) in an Israeli study were defined as those who had visited physicians at
with high patient numbers.3 Recently, a United least 5 times between 2009 and 2013 with such
Kingdom population-based study reported that ro- symptoms; the physicians had assigned the relevant
sacea was significantly more prevalent in patients International Statistical Classification of Disease,
with IBD than others,4 and another study reported 10th Revision codes to their principal diagnoses.
an association between IBD and AD.5 These re-
lationships might be ex- Statistical analysis
plained by overlaps in the We calculated adjusted ORs
immunologic characteristics CAPSULE SUMMARY and 95% confidence intervals
that trigger either condition, (CIs) using multivariable logis-
d An overlap between the causes of
similarities in the environ- tic regression modeling after
inflammatory bowel disease and other
mental triggers of disease, adjusting for age and sex. We
immune systememediated diseases has
shared genetic risk loci, or a also performed sensitive ana-
long been suspected.
combination of these. lyses after further adjustment
We sought to identify the d Patients with inflammatory bowel for the type of insurance car-
risks for ISDs, including psori- disease may be at an increased risk of ried to assess the robustness of
asis, rosacea, and AD, and inflammatory skin diseases. our results. We performed
autoimmune skin diseases d Increased concern for signs of skin subsequent subgroup ana-
(ASDs), including vitiligo and diseases in patients with inflammatory lyses in terms of sex and age
alopecia areata (AA), in pa- bowel disease may be warranted. group. All data were analyzed
tients with versus without using software (SAS, Version
IBD. We interrogated the data- 9.4, SAS Institute, Cary, NC).
base of the Korean National Health Insurance (NHI) Ethics
service to this end. We also examined the effects of age The work was approved by the institutional review
and sex on the associations between IBD and ISDs. board of St Vincents Hospital and adhered to all tenets
of the Declaration of Helsinki (VC15EISI0173).
METHODS
Data sources RESULTS
We conducted a nationwide cross-sectional study Characteristics of patients with IBD and
using 2009 to 2013 data from the Korean NHI control subjects
database. In Korea, all citizens are compulsorily We identified a total of 40,843 patients with IBD,
registered in the NHI system, which offers affordable including 12,646 patients with CD and 28,197 with
universal health insurance with easy access to medical UC, and 122,529 control subjects without IBD. The
services. In 2013, the NHI system covered 97.2% of the control subjects were frequency-matched in terms of
population (n = 49,989,620). The NHI database age and sex to patients with IBD. The mean subject
contains data on all NHI claims; these data include age was 41.2 years, and 60.2% of subjects of either
patient age, sex, diagnosis, and prescribed drugs. group were male. The baseline characteristics of all
subjects are summarized in Table I.
Study population
We identified all patients with IBD given a Associations between IBD and ISDs
diagnosis from 2009 to 2013 by reference to the After adjusting for age and sex, patients with IBD
codes of the International Statistical Classification were at an increased risk of rosacea (OR 2.173, 95%
of Disease, 10th Revision (K50 for CD and K51 for CI 1.590-2.969), psoriasis (OR 1.778, 95% CI 1.580-
UC). To minimize misclassification errors, we 2.161), and AD (OR 1.366, 95% CI 1.257-1.485),
included only patients who had visited physicians compared with control subjects (Table II).
at least 5 times. The control group was selected
randomly from age- and sex-matched patients Associations between IBD and ASDs
without IBD who had undergone surgery to treat Patients with IBD were at a somewhat increased
hemorrhoids within the same period. risk of vitiligo (OR 1.200, 95% CI 0.967-1.486), but
this was not significant. In addition, patients with
Concurrent skin diseases IBD were at a decreased risk of AA compared with
The outcomes of interest were concurrent skin healthy control subjects (OR 0.861, 95% CI 0.766-
diseases including ISDs (psoriasis, AD, and rosacea) 0.967); this was especially true of patients with CD
and ASDs (vitiligo and AA). To improve the accuracy (OR 0.603, 95% CI 0.485-0.749) (Table II).
J AM ACAD DERMATOL
VOLUME jj, NUMBER j
Abbreviations used:
AA: alopecia areata
AD: atopic dermatitis
ASD: autoimmune skin diseases
CD: Crohns disease
CI: confidence interval
IBD: inflammatory bowel disease
IL: interleukin
ISD: inflammatory skin disease
NHI: National Health Insurance
OR: odds ratio
Th: T-helper
UC: ulcerative colitis
Associated diseases stratified by sex and age
Upon subgroup analysis by sex, male patients
with IBD were at a higher risk of rosacea than were
female patients, whereas the risk of psoriasis was
more significant in female than male patients with
IBD (Table III). Stratified by age, patients younger
than 30 years were at increased risks of psoriasis (OR
2.063, 95% CI 1.584e2.687 for UC; OR 1.914, 95% CI
1.479e2.476 for CD), rosacea (OR 3.341, 95% CI
1.396e7.996 for UC; OR 5.301, 95% CI 2.440e11.517
for CD), and AD (OR 1.703, 95% CI 1.463e1.982
for UC; OR 1.305, 95% CI 1.127e1.511 for CD)
(Table III). CD and UC were separately associated
with ISDs.
DISCUSSION
We performed a population-based case-control
study on 39,353 patients with IBD and 77,947 control
subjects to evaluate the associations between IBD
and various skin diseases. Patients with IBD were at
significantly increased risks of ISDs, including pso-
riasis, rosacea, and AD, whereas lower or nonsignif-
icant associations were evident between IBD and
ASDs including vitiligo and AA.
Our findings are consistent with those of previous
epidemiologic studies on the association between
psoriasis and IBD. In a United Kingdom study on 136
patients with CD, the incidence of psoriasis was 9.6%
compared with 2.2% in control subjects, and 10% of
patients with CD had family histories of psoriasis in
first-degree relatives compared with 2.9% of control
subjects.6 In a study on 8072 adults with IBD (3879
UC and 4193 CD), increased risks of psoriasis were
evident in both patients with UC and CD compared
with control subjects.7 In 1982, Yates et al8 showed
that the prevalence of psoriasis in patients with CD
(11.2%) and UC (5.7%) was significantly higher than
that in control subjects (1.5%). In a study on 12,502
patients with psoriasis and 24,287 control subjects,
psoriasis was significantly more common in patients
with IBD, more so in patients with CD (OR 2.49) than
UC (OR 1.64).3 Recently, a study in a nationwide
Kim et al 3
Danish cohort showed that the risk of development
of severe psoriasis was higher in patients with CD
and UC.9 We found that psoriasis was 1.78-fold more
common in patients with IBD than control subjects,
but the ORs for patients with UC and CD were similar
(OR 1.77, 95% CI, 1.58-1.98 for UC; OR 1.81, 95% CI,
1.54-2.12 for CD). Our results confirm that IBD is
significantly associated with psoriasis. To our knowl-
edge, this is the first relevant study using a national
Asian database.
An association between IBD and psoriasis is
theoretically plausible; both diseases are thought to
be chronic inflammatory conditions sharing a
T-helper (Th)1/Th17 cell-mediated inflammatory
pathogenesis developing at the surface of the skin
or the intestinal mucosal barrier.10 Cytokines (ie,
tumor necrosis factor-a, interleukin [IL]-23, IL-17, and
IL-22) and Th17 cells appear to play major roles in the
pathogenesis of both psoriasis and IBD.11,12 IL-23
enhances the survival and proliferation of Th17 cells.
IL-23 is essential for inflammatory infiltration of
lesional psoriatic skin by Th17 cells and for induction
of chronic intestinal inflammation in patients with
IBD.11,13,14 Changes in Th17 cell numbers have been
suggested to play a role in IBD; both IL-23 and IL-17
are overexpressed in the inflamed mucosa of patients
with IBD.12,13 In patients with psoriasis, Th17-
derived cytokines including IL-17 and IL-22 promote
acanthosis, hyperkeratosis, parakeratosis, and the
synthesis of inflammatory mediators within the
dermis and epidermis.10,11 In such patients, the levels
of messenger RNAs encoding IL-17, IL-23p19,
IL-23p40, and IL-6 were significantly higher in pso-
riatic lesions than nonlesional skin, as was the num-
ber of Th17 cells.15,16
In addition to the immunologic similarities be-
tween IBD and psoriasis, recent work has shown that
the genetic susceptibilities to the 2 diseases over-
lap.14,17 Genomewide association studies have
shown that IL-23R gene polymorphism is associated
with both IBD and psoriasis, confirming that IL-23
signaling plays a role in the pathological
Th17-mediated inflammation shared by IBD and
psoriasis.18,19 Ustekinumab, a human monoclonal
antibody targeting the p40 subunit of IL-12 and IL-23,
effectively treats both IBD and psoriasis.20 We found
it intriguing that the OR for psoriasis development
was higher in younger (age \30 years) than older
(age [30 years) patients with IBD. This is further
evidence for a common genetic background be-
tween patients with IBD and psoriasis; both condi-
tions tend to develop early in life.
We found that rosacea had the highest prevalence
in patients with IBD relative to control subjects; the
prevalence of rosacea was 2.2-fold higher in patients
4 Kim et al J AM ACAD DERMATOL
n 2016

Table I. Characteristics of the study population

Healthy control, n = 122,529 IBD, n = 40,843 UC, n = 28,197 CD, n = 12,646
Mean age 6 SD, y 41.2 6 17.2 41.2 6 17.2 45.1 6 16.1 32.5 6 16.1
Age distribution, y
\10 489 (0.4%) 163 (0.4%) 70 (0.2%) 93 (0.7%)
10-19 12,423 (10.1%) 4141 (10.1%) 1409 (5.0%) 2732 (21.6%)
20-29 23,508 (19.2%) 7836 (19.2%) 3912 (13.9%) 3924 (31.0%)
30-39 24,129 (19.7%) 8043 (19.7%) 5440 (19.3%) 2603 (20.6%)
40-49 22,713 (18.5%) 7571 (18.5%) 6201 (22.0%) 1370 (10.8%)
50-59 18,987 (15.5%) 6329 (15.5%) 5470 (19.4%) 859 (6.8%)
60-69 12,174 (9.9%) 4058 (9.9%) 3495 (12.4%) 563 (4.5%)
70-79 6711 (5.5%) 2237 (5.5%) 1852 (6.6%) 385 (3.0%)
$80 1395 (1.1%) 465 (1.1%) 348 (1.2%) 117 (0.9%)
Sex
Male 73,776 (60.2%) 24,592 (60.2%) 15,848 (56.2%) 8744 (69.1%)
Female 48,753 (39.8%) 16,251 (39.8%) 12,349 (43.8%) 3902 (30.9%)
Type of health insurance program
National health insurance 121,356 (99.0%) 39,366 (96.4%) 27,273 (96.7%) 12,093 (95.6%)
Medical aid 1173 (1.0%) 1477 (3.6%) 924 (3.3%) 553 (4.4%)

CD, Crohns disease; IBD, inflammatory bowel disease; UC, ulcerative colitis.

with IBD than control subjects. A few studies earlier
reported associations between rosacea and IBD.4,21
In a survey of 80,957 patients with rosacea in the
United Kingdom, the condition was significantly
more common in patients with IBD, and the associ-
ation between UC and rosacea was stronger in
patients younger than 45 years.4 These associations
have been attributed to Th1/Th17-induced polarized
inflammation, expression of cathelicidin LL-37 in
both rosacea and IBD, and shared genetic and
environmental risk factors.22-25 Indeed, the level of
cathelicidin LL-37, an antimicrobial peptide that
plays a crucial role in rosacea pathogenesis, was
significantly elevated in the colon mucosa of patients
with IBD. Recent genetic studies have shown that a
certain major histocompatibility complex class II
protein-encoding gene (the gene for HLA-
DRB1*03:01) is associated with rosacea, and this
gene also plays an important role in IBD pathogen-
esis.26-28 Our findings are consistent with those of
previous studies; we found an association between
rosacea and IBD. In addition, an immune response-
related genetic susceptibility to disease may be at
play in both IBD and rosacea.
We found that patients with IBD were at increased
risk of AD (OR 1.366, 95% CI 1.257-1.485), consistent
with the results of a large cohort study performed in
Germany.5 AD is a chronic, relapsing, inflammatory
skin condition caused by dysfunction of the
epidermal barrier and immune systememediated
inflammation; AD affects 7-10% of Asian adults.29-33
Although deviation from the Th2 immune response
is closely related to AD development, growing evi-
dence indicates that Th17 cells are also involved in
the immunopathogenesis of the condition.34 When
European-American and Asian (Japanese and
Korean) patients with AD were compared, the
Asian patients exhibited a more dominant Th17
phenotype (associated with reduced Th2 expres-
sion), and much greater induction of Th17/IL-23 axis
genes, than did European-American patients with
AD.35 We found a strong association between IBD
and AD, suggesting that Korean patients with AD
tend to express a Th17 phenotype.
We did not observe any significant associations
between IBD and ASDs such as vitiligo and AA.
These are commonly regarded as autoimmune
disorders mediated by autoimmune mechanisms,
thus pathogenic autoantibody production by B and
autoreactive T cells.36-38 Co-occurrence of vitiligo,
AA, and other autoimmune conditions is common,
further supporting the autoimmune nature of these
diseases.39-42 AA may present as an independent
immune-mediated disease concomitant with IBD, it
may be a manifestation of underlying IBD, or it may
even be a paradoxical reaction to tumor necrosis
factor-a antagonists including infliximab and adali-
mumab.43-46 As hair loss by patients with IBD may be
caused by various factors, identification of the cor-
rect cause is not always possible.47 An association
between IBD and AA is further supported by several
studies showing an increased risk of UC among
patients with AA.48,49 However, a large Taiwanese
study on patients with AA and a US survey of 513
patients with AA did not find that IBD was associated
with a significantly higher prevalence of AA.42,50 We
did not observe a significantly increased prevalence
of AA or vitiligo in patients with either UC or CD.
Table II. Associations between inflammatory bowel disease and immune systememediated skin diseases

VOLUME jj, NUMBER j

J AM ACAD DERMATOL
Univariable analysis Multivariable analysis Sensitivity analysis
Prevalence Crude OR (95% CI) P value Adjusted OR (95% CI)* P value Adjusted OR (95% CI)y P value
Psoriasis
Healthy control 0.88% (1097/122,529) Reference Reference Reference
IBD 1.56% (636/40,843) 1.780 (1.613-1.965) \.0001 1.778 (1.611-1.963) \.0001 1.765 (1.598-1.949) \.0001
Rosacea
Healthy control 0.08% (94/122,529) Reference Reference Reference
IBD 0.10% (68/40,843) 2.172 (1.590-2.968) \.0001 2.173 (1.590-2.969) \.0001 2.135 (1.559-2.925) \.0001
Atopic dermatitis
Healthy control 1.49% (1827/122,529) Reference Reference Reference
IBD 2.02% (826/40,843) 1.364 (1.256-1.482) \.0001 1.366 (1.257-1.485) \.0001 1.347 (1.239-1.465) \.0001
Vitiligo
Healthy control 0.24% (293/122,529) Reference Reference Reference
IBD 0.29% (117/40,843) 1.199 (0.967-1.486) .0981 1.199 (0.967-1.486) .0980 1.200 (0.967-1.489) .0975
Alopecia areata
Healthy control 1.05% (1285/122,529) Reference Reference Reference
IBD 0.91% (370/40,843) 0.863 (0.768-0.969) .0126 0.861 (0.766-0.967) .0116 0.854 (0.760-0.960) .0082

Psoriasis
Healthy control 0.88% (1079/122,529) Reference Reference Reference
UC 1.61% (453/28,197) 1.838 (1.646-2.053) \.0001 1.767 (1.581-1.975) \.0001 1.756 (1.571-1.963) \.0001
CD 1.45% (183/12,646) 1.653 (1.412-1.935) \.0001 1.806 (1.539-2.119) \.0001 1.786 (1.521-2.097) \.0001
Rosacea
Healthy control 0.08% (94/122,529) Reference Reference Reference
UC 0.16% (46/28,197) 2.128 (1.496-3.029) \.0001 1.979 (1.389-2.819) .0002 1.952 (1.368-2.785) .0002
CD 0.17% (22/12,646) 2.270 (1.427-3.613) .0005 2.735 (1.708-4.380) \.0001 2.666 (1.659-4.284) \.0001
Atopic dermatitis
Healthy control 1.49% (1827/122,529) Reference Reference Reference
UC 1.82% (512/28,197) 1.222 (1.107-1.349) \.0001 1.362 (1.233-1.505) \.0001 1.347 (1.219-1.488) \.0001
CD 2.48% (314/12,646) 1.682 (1.490-1.899) \.0001 1.373 (1.215-1.553) \.0001 1.348 (1.192-1.525) \.0001
Vitiligo
Healthy control 0.24% (293/122,529) Reference Reference Reference
UC 0.27% (76/28,197) 1.127 (0.876-1.452) .3519 1.109 (0.860-1.429) .4247 1.078 (0.493-2.360) .4205
CD 0.32% (41/12,646) 1.358 (0.979-1.883) .0669 1.410 (1.012-1.964) .0421 2.804 (1.081-7.277) .0416
Alopecia areata
Healthy control 1.05% (1285/122,529) Reference Reference Reference

Kim et al 5
UC 1.00% (281/28,197) 0.950 (0.834-1.081) .4360 0.996 (0.874-1.135) .9520 0.989 (0.868-1.128) .8708
CD 0.70% (89/12,646) 0.669 (0.539-0.830) .0003 0.603 (0.485-0.749) \.0001 0.596 (0.480-0.741) \.0001

CD, Crohns disease; CI, confidence interval; IBD, inflammatory bowel disease; OR, odds ratio; UC, ulcerative colitis.
*Adjusted by age.
y
Adjusted by age and insurance type.
 6 Kim et al
Table III. Subgroup analyses of the association between immune systememediated skin diseases and either form of inflammatory bowel disease by age
and sex
Psoriasis Rosacea Atopic dermatitis Vitiligo Alopecia areata
Adjusted OR (95% CI)* P value Adjusted OR (95% CI)* P value Adjusted OR (95% CI)* P value Adjusted OR (95% CI)* P value Adjusted OR (95% CI)* P value
Male
Healthy control Reference Reference Reference Reference Reference
UC 1.531 (1.325-1.769) \.0001 2.595 (1.586-4.245) .0001 1.315 (1.141-1.514) .0001 1.321 (0.942-1.851) .1061 0.984 (0.827-1.172) .8584
CD 1.576 (1.286-1.932) \.0001 3.027 (1.572-5.827) .0009 1.456 (1.251-1.694) \.0001 1.256 (0.805-1.959) .3150 0.633 (0.490-0.818) .0005
Female
Healthy control Reference Reference Reference Reference Reference
UC 2.169 (1.820-2.587) \.0001 1.485 (0.886-2.489) .1336 1.401 (1.217-1.614) \.0001 0.909 (0.619-1.337) .6293 1.009 (0.828-1.229) .9302
CD 2.505 (1.934-3.244) \.0001 2.597 (1.313-5.137) .0061 1.242 (1.005-1.535) .0445 1.666 (1.015-2.735) .0434 0.537 (0.356-0.811) .0031
Age \30 y
Healthy control Reference Reference Reference Reference Reference
UC 2.063 (1.584-2.687) \.0001 2.854 (0.972-8.385) .0564 1.703 (1.463-1.982) \.0001 0.964 (0.538-1.728) .9030 1.330 (1.039-1.702) .0233
CD 1.914 (1.479-2.476) \.0001 5.709 (2.306-14.132) .0002 1.305 (1.127-1.511) .0004 1.281 (0.803-2.044) .2989 0.777 (0.580-1.040) .0895
Age 30-49 y
Healthy control Reference Reference Reference Reference Reference
UC 1.667 (1.395-1.992) \.0001 1.989 (1.087-3.640) .0258 1.425 (1.189-1.708) .0001 1.353 (0.887-2.064) .1610 0.881 (0.733-1.057) .1731
CD 1.883 (1.447-2.450) \.0001 3.072 (1.343-7.027) .0078 1.135 (0.830-1.551) .4274 2.038 (1.152-3.605) .0144 0.496 (0.339-0.726) .0003
Age $50 y
Healthy control Reference Reference Reference Reference Reference
UC 1.697 (1.434-2.008) \.0001 1.581 (0.956-2.616) .0745 1.103 (0.907-1.342) .3265 1.031 (0.703-1.512) .8764 0.818 (0.617-1.084) .1615
CD 1.875 (1.340-2.622) .0002 1.246 (0.388-4.004) .7118 1.584 (1.113-2.254) .0106 0.880 (0.359-2.157) .7799 0.746 (0.383-1.453) .3887

CD, Crohns disease; CI, confidence interval; OR, odds ratio; UC, ulcerative colitis.
*Adjusted by age.

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Indeed, AA was less common in patients with CD
than in control subjects (OR 0.603, 95% CI 0.485-
0.749). We suggest that this may be attributed to the
frequent use of immunomodulators (including
azathioprine, its metabolite 6-mercaptopurine, and
methotrexate) by patients with CD; these medica-
tions exert immunomodulatory effects on AA.51,52
Further studies are needed to establish whether these
drugs decrease the risk of AA or if, on the contrary,
the immunologic mechanisms at play in CD are
related to the observed effect on the AA risk. In fact,
various immunomodulatory drugs, including azathi-
oprine, mycophenolate mofetil, and methotrexate,
are also used to treat inflammatory skin conditions
such as AD and psoriasis, which had a higher
incidence in patients with IBD. Nevertheless, the
immunologic similarities and overlapping genetic
background between IBD and ISDs such as psoriasis
and AD might be reasons for the increased in-
cidences of ISDs in the IBD group, despite the
frequent use of immunomodulatory drugs in patients
with IBD.
Our study had several limitations. First, we did not
evaluate any environmental or lifestyle factors (eg,
smoking status, alcohol consumption, dietary data,
residence in rural/urban areas, or antibiotic use) that
may contribute to the development of IBD. We also
did not evaluate treatment modalities. This was
because the insurance claims database contains
only limited diagnostic and clinical information. In
addition, we could not identify the reason for the
association between IBD and ISDs because of the
observational nature of our study; our results may be
attributed to unmeasured confounding factors.
Second, we missed many cases of rosacea, because
rosacea is not covered by the insurance system of
Korea. Nevertheless, we thought it worthwhile to
compare the ORs between the 2 groups. Third, we
divided immune systememediated skin diseases
into 2 groups (ISDs and ASDs) based on clinical
and immunologic features. This distinction is un-
clear; some immunologic overlap may be at play.
However, we found that we could explain the nature
of diseases associated with IBD more clearly when
we made this distinction. Although our study had
several limitations, this was a large-scale, nation-
wide, population-based work on the incidence of
ISDs in patients with IBD. Fourth, we could not
distinguish between the various phenotypes and
severities of ISDs including AD, psoriasis, and rosa-
cea. Furthermore, it has been reported that psoriasis
severity and phenotype may differ between patients
with IBD and healthy control subjects.53 Finally,
because our control group consisted of patients
undergoing surgery for hemorrhoids without a
Kim et al 7
diagnosis of IBD, there is a possibility of the under-
estimation of the association of IBD and skin disease.
Some have suggested hemorrhoids can be a sign of
IBD that may precede internal involvement, and this
is especially of concern in children who may have
hemorrhoidal tags as a first sign of IBD. However,
this condition is rare and unlikely to affect our
findings, given that patients younger than 10 years
comprised a very small proportion of both the
control and IBD groups (0.4%). Therefore, we
believe that the control group would not contribute
to any underestimation of the association between
IBD and skin disease.
In conclusion, our current, population-based,
cross-sectional study suggests that IBD is associated
with increased risks of ISDs including psoriasis, rosa-
cea, and AD, but not ASDs including vitiligo and AA.
This may be attributed to similarities in the genetic
susceptibilities and immune systememediated
inflammation of patients with IBD and ISDs. These
diseases are thought to be chronic inflammatory
disorders of the surfaces of the intestinal mucosa and
skin, respectively; both tissues are complex barriers
separating the inner body from the environment. A
role for chronic inflammation in both conditions is
suggested by the co-occurrence of chronic inflamma-
tory conditions of the skin and bowel. Further work on
the association between ISDs and IBD may allow us to
better understand the immunologic background of
both diseases and to reduce the burden of comorbid
ISDs in patients with IBD.
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