Northeast Florida Medicine Journal, Winter 2015

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40 Vol. 66, No. 4 2015 Northeast Florida Medicine DCMS online . org
Inflammatory Bowel Disease
arthritis, erythema nodosum, pyoderma gangrenosum,
aphthous stomatitis, and the ocular findings of iritis
and uveitis. The second category includes autoimmune
diseases that appear to be independent of the underly-
ing bowel disease and may reflect only a susceptibility
to autoimmunity. These disorders are not considered as
specific features but as autoimmune associated diseases
and include ankylosing spondylitis, primary sclerosing
cholangitis, primary biliary cirrhosis, alopecia areata, and
thyroid autoimmune disease.1
Pathogenesis of Immune Related
Extraintestinal Manifestations in IBD
Evidence from many studies in genetically susceptible
animal models of colitis suggest a crucial role of enteric
flora in activating the immune system against bacterial
antigens and against portions of the colonic mucosa on
the basis of an antigenic cross reactivity.2 The sharing of
these colonic antigens by extraintestinal organs, associated
with a genetic susceptibility, would eventually lead to an
immune attack on these organs. One prime example is
seen in primary sclerosing cholangitis, most commonly
associated with ulcerative colitis. In that disorder, the
presence of anticolonic mucosal autoantibodies cross react
with biliary epithelium. In addition, a colonic epithelial
protein and the human tropomyosin isoform 5, which
are not only expressed in the colon but also in the biliary
tract, skin, eyes, joints, have been suspected to be the major
common targets of autoimmune attack in the extraintestinal
organs of IBD patients. It is unclear why the extraintestinal
organs are not always involved at the same time and why
these autoantibodies are absent in colonic Crohn’s disease.
A partial explanation is that the genetic factors or local
co-existent damage factors, such as infection and trauma,
could regulate the display of these cryptic antigens and
the susceptibility to autoimmune attack.
As part of inflammatory bowel disease in general, a
physician can identify an immune induction site where
T cells are primed, represented by the colon and the ef-
fector sites that are the extraintestinal organs. Immune
cells infiltrate the effector sites with the help of adhesion
molecules such as alpha-4 B7 integrin and vascular adhe-
sion protein that have a cytokine-mediated overexpression
Introduction
The inflammatory bowel diseases (IBD), notably Crohn’s
disease (CD) and ulcerative colitis (UC) are chronic,
debilitating, systemic inflammatory diseases that may
involve the entire gastrointestinal tract. Between 30 and
40 percent of patients with IBD develop extraintestinal
inflammation and clinically significant disorders termed
extraintestinal manifestations (EIM).1 The most common
EIMs affect the joints, skin, eyes, and biliary tract. Many
times, the EIMs associated with these inflammatory dis-
eases bear a very negative impact on the overall course of
the disease. Therefore, it is very important to identify the
particular extraintestinal disorder and treat it accordingly,
as well as treat the underlying inflammatory bowel disease.
At times, certain EIMs such as axial arthritis, pyoderma
gangrenosum, uveitis, and primary sclerosing cholangitis
run a very independent clinical course. With the advent
of the biologic response modifiers such as the anti-TNF
inhibitors, we have seen marked improvement in these
extraintestinal manifestations.
Extraintestinal IBD-related immune diseases can be
classified into two major groups: The first includes reactive
manifestations associated with intestinal inflammatory
activity and therefore reflect a pathogenic mechanism
common with the intestinal disease. These include
The Extraintestinal Manifestations
of Inflammatory Bowel Disease
By John M. Petersen, DO, FACG, FACP
Address Correspondence to:
John M. Petersen, DO, FACG, FACP
Borland-Groover Clinic
4800 Belfort Road
Jacksonville, FL 32256
Abstract: Inflammatory bowel disease (IBD) is associated with
a variety of extraintestinal manifestations that may produce more
morbidity than the underlying intestinal disease, and pre or post date
the presentation or activity of IBD. Nearly 40 percent of patients
with IBD will have at least one of these features. Some are related to
the underlying inflammation (joint, skin, ocular, oral). Others are
seen in small bowel dysfunction (gallstones, kidney stones, obstructive
uropathy). Osteoporosis, anemia, hepatobiliary disease, fistulas,
amyloidosis, and neuropathy may be seen. A number of pathogenetic
mechanisms play a role in their development. Early recognition is
paramount to avoid potential morbidity and mortality.