Case 5 -
Crohn's Ileitis with Superimposed Giant Cell Arteritis Involving Mesenteric Arteries
University of Chicago Hospitals
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The patient is a 15-year-old male with a several year history of Crohn's disease. The patient has
been treated in the past with steroids and infliximab. Recently obstructive symptoms led to a small
bowel follow through, which revealed a tight stricture in the terminal ileum. An ileocecectomy was
performed. Gross examination of the specimen documented a 3 cm stricture of the distal terminal ileum
with linear ulcers and effacement of the usual mucosal fold pattern. The cecum and appendix were grossly
unremarkable. A representative section from the ileal stricture is provided for review.
Case 5 - Slide 1
Case 5 - Figure 1 - Low power of ileal section revealing thickened wall and transmural inflammatory changes typical of Crohn's disease
Case 5 - Figure 2 - Medium power of above highlighting mucosal architectural distortion and submucosal fibrosis.
Case 5 - Figure 3 - Medium power of above to demonstrate neuronal hyperplasia, and serosal granulomas and lymphoid follicles.
Case 5 - Figure 4 - Low power of medium sized mesenteric artery included in the ileocecetomy specimen, reveal occusion due to intimal hyperplasia and fibrosis.
Case 5 - Figure 5 - Medium power demonstrating active arteritis.
Case 5 - Figure 6 - High power reveal multinucleated giant cells and disruption of the elastica.
Case 5 - Figure 7 - Another mesentery artery exhibiting active giant cell arteritis and surrounded by granulomatous inflammation.
Case 5 - Figure 8 - Another mesenteric artery exhibiting active giant cell arteritis.
Sections reveal classic histologic features of Crohn's disease, including mucosal ulceration in a
background of mucosal architectural distortion, submucosal fibrosis, neuronal hyperplasia, scattered
granulomas, and transmural inflammatory changes. In addition, there is a giant cell arteritis affecting
mesenteric arterial branches, with disruption of the elastica, intimal hyperplasia and fibrosis, and
dystrophic microcalcifications. However, ischemic changes are not evident in the overlying bowel.
Crohn's ileitis with superimposed giant cell arteritis involving mesenteric arteries.
Crohn's Disease and Vasculitis
Patients with Crohn's disease can develop a wide range of extraintestinal manifestations, including
vasculitis. In addition, a number of vascular changes have been described within the intestine itself in
Crohn's disease, some of which are thought to be important in the pathogenesis of the disorder.
Patients with Crohn's disease sometimes present initially with signs and symptoms due to vasculitis
involving an extraintestinal site (skin, retina, skeletal muscle), or develop vasculitis in one of these
organs after the diagnosis of Crohn's is established
A diagnosis of primary systemic vasculitis
is not warranted in such cases because: 1) multiorgan involvement by the vasculitic process is not
evident, and 2) the gastrointestinal disease is typical of Crohn's disease, with no evidence of
vasculitis or ischemic changes. The histologic features of the vasculitis involving the extraintestinal
site are variable, as is the size of vessel involved. Treatment of the Crohn's disease is usually
effective in suppressing the vasculitic component as well.
Laboratory evaluation in patients with colonic Crohn's disease not infrequently reveals an elevated
titer of perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA). The specificity of these
autoantibodies in terms of a neutrophil organelle or protein target are not well studied, and appear to
vary among different patient populations. These autoantibodies should be clearly separated from the
cytoplasmic anti-neutrophil cytoplasmic antibodies (c-ANCA) that are almost always found in elevated
titer in patients with small vessel systemic vasculitis
These autoantibodies, which are known to
be directed against either myeloperoxidase or proteinase 3, are almost never present in elevated titer in
patients with idiopathic inflammatory bowel disease (IBD). Nonetheless, in both systemic vasculitis and
IBD the formation of the anti-neutrophil autoantibodies is believed to be related to the apoptotic
destruction of these cells, and the antibodies may in fact play a role in the pathogenesis of these
System Vasculitis Misdiagnosed as Crohn's Disease
Many patients with systemic vasculitides originally present with symptoms and signs that closely
resemble those typical of inflammatory bowel disease. Because gastrointestinal involvement by vasculitis
often is segmental, with intervening "skip areas" of normal bowel, a close radiographic and histologic
resemblance to Crohn's disease is also possible. In particular, Behçet's disease, polyarteritis nodosa,
and microscopic polyangiitis must be considered in patients diagnosed with Crohn's disease with atypical
clinical, radiographic or histologic features . The proper recognition of gastrointestinal vasculitis
may be difficult because the affected vessels are difficult to visualize radiographically (owning to
their small size) and are difficult to access by biopsy (due to their submucosal location). A recent
study reported on ten children who presented with abdominal pain, weight loss, diarrhea (bloody in six)
and exhibited patchy mucosal ulceration by endoscopy . Biopsies were read as consistent with
inflammatory bowel disease in five of the patients, and non-specific changes in the remaining five.
Further work-up over the next 2 to 24 months revealed either radiographic or pathologic evidence of
systemic vasculitis (polyarteritis nodosa in nine and microscopic polyangiitis in one). The authors
emphasized the importance of visceral angiography in the proper diagnosis of systemic vasculitides, but
noted that the classic diagnostic changes may not be present in patients already treated with
immunosuppressive drugs for presumed IBD. Instead, more subtle (non-aneurysmal) changes must be regarded
as consistent with vasculitis by the radiologist. Biopsies of other organs can also be very helpful in
documenting vasculitis (skin, kidney, skeletal muscle).
Gastrointestinal involvement by Behçet's disease can closely resemble Crohn's disease radiographically
(focal mucosal ulcerations most commonly of the ileocecal region, stricture formation) and histologically
(focal transmural inflammatory changes, granulomas (?), submucosal fibrosis). The extraintestinal
manifestations of Behçet's disease (oral and genital ulcers, eye changes etc.) are the key to proper
Giant Cell Arteritis, Takayasu's Arteritis and Crohn's Disease
Giant cell arteritis and Takayasu's arteritis are two of the three known systemic vasculitides that
primarily affect large arteries (Kawasaki's arteritis is the third). These two forms of vasculitis are
histologically indistinguishable, and the differential diagnosis rests upon the age at presentation, the
site(s) of involvement, and the presenting
In general, cases are classified as
Takayasu's arteritis when the patient presents at an age of less than 40 years, and when there are
symptoms and radiographic evidence of involvement of the major branches of the proximal aorta. Giant
cell arteritis is diagnosed primarily in older individuals with involvement of large cranial arteries
(especially the temporal artery). Involvement of the gastrointestinal tract by giant cell arteritis or
Takayasu's arteritis is rare, occurring in less than 1% and about 10% of cases respectively
Gastrointestinal involvement is caused by active vasculitis of large mesenteric vessels resulting in
ischemia, and is usually diagnosed by angiography.
An association between intestinal Crohn's disease and large vessel arteritis has been noted
sporadically in the literature since the early 1970s, usually in the form of individual case reports or
small series, for a total of about 50 patient. In most of these cases the vasculitis is classified as
since the patients are diagnosed before the age of forty years, and exhibit
symptoms and radiographic evidence of involvement of branches of the proximal aorta, as well as
mesenteric vessels. In about half of the cases the arteritis is diagnosed first, while in the other half
the patient has an established diagnosis of Crohn's disease and then develops vasculitis involving the
aorta or its large proximal branches. Interestingly, gastrointestinal ischemia is not described in any
of these cases, and in fact the mesenteric arteries do not appear to be affected. Instead, the two
disease processes appear to run separate courses and do not impact significantly on one another. There
appears to be only one previously reported case similar to the patient discussed here, in which giant
cell arteritis is documented histologically to involve mesenteric vessels supplying intestine affected by
Crohn's disease . In that report, as in the current case, there were no ischemic changes in the
bowel and no symptoms of vasculitis involving the aorta or its major branches.
Vascular Changes in Intestinal Crohn's Disease
Although often overlooked today, granulomatous lymphangitis was highlighted as a key histologic
feature in the early systematic descriptions of the microscopic pathology of Crohn's disease
landmark review published in 1954 of the experience of the New England Deaconess Hospital Department of
Pathology concluded that "
the chief disease process is a progressive granulomatous lymphangitis. It
affects and scleroses lacteals in the intestinal lamina propria
and similarly affects lymphatics in the
intestinal submucosal, muscular, and subserosal layers . All of these reports included
photomicrographs demonstrating granulomas involving or impinging on dilated lymphatic channels. Emphasis
of this histologic finding waned until 1991, when Wakefield et al, utilizing a perfusion fixation
technique, again noted the close association of granulomas and vascular structures in the intestinal
wall, and proposed that granulomatous vasculitis was an important element of the pathogenesis of Crohn's
disease . At the time these investigators were unsure if the granulomatous inflammation primarily
affected arterial, venous, or lymphatic channels
but subsequent studies have focused on the
involvement of the lymphatics
Wakefield later developed an animal model of microvascular occlusion that recapitulated some of the
histologic features of Crohn's disease, providing some additional evidence for a vasculitic component in
the pathogenesis of the disease
Subsequently Wakefield claimed that measles virus infection of
endothelial cells could be responsible for development of the granulomatous lymphangitis and that
atypical measles infection at an early age might even be the cause of Crohn's disease
investigators have been unable to identify measles virus in intestinal tissues from Crohn's disease
patients, and epidemiologic studies have failed to find convincing evidence that measles infection
increases the risk for Crohn's disease
Nonetheless, the observation that granulomatous
vasculitis is a consistent feature of Crohn's disease is valid, although the significance and underlying
cause remain elusive.
Aphthous erosions and micro-ulcerations are regarded as among the earliest histologic features of
Crohn's disease, and there is some evidence that microvascular damage leading to mucosal ischemia may
play a part in the formation of these lesions. In situ fluorescent
endoscopy has demonstrated subtle microvascular abnormalities in otherwise endoscopically normal mucosa
in Crohn's patients , and perfusions studies have confirmed capillary wall damage beneath aphthous
lesions . Additional studies have documented pathologic changes in larger vessels beneath linear
Radiographic studies have also confirmed dimunition of blood flow to bowel segments
affect by Crohn's disease . However, all of the investigators involved in this area recognize that
it is difficult to determine whether these vascular changes precede or are a consequence of the
inflammatory changes that are occurring in the surrounding tissues.
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