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DOI 10.1007/s10620-010-1126-4
ORIGINAL ARTICLE
Received: 26 August 2009 / Accepted: 11 January 2010 / Published online: 29 January 2010
Springer Science+Business Media, LLC 2010
Abstract
Background The reported prevalence of cytomegalovirus
(CMV) infection with active inflammatory bowel disease
(IBD) is highly variable, and whether CMV negatively
impacts the clinical course is controversial.
Aims The aim of this study was to determine the prevalence of CMV in patients with active ulcerative colitis
(UC) or Crohns disease (CD) and compare the course of
disease in patients with and without CMV.
Methods Consecutive patients with acute exacerbations
of active IBD colitis had immunohistochemistry staining
for CMV antigen performed on archived specimens. Clinical features were retrospectively reviewed.
Results Twelve (10%) of 122 UC patients had CMV, and
0/20 patients with CD had CMV. Of 12 UC patients with
CMV infection, seven were not taking steroids or immunosuppressives at their index flare. UC patients with CMV
were more likely to have leukocytosis (OR = 5.3, 95% CI
1.518.2), require hospitalization (OR = 4.9, 95% CI 1.2
19.0), and be hospitalized C7 days (OR = 5.0, 95% CI
1.621.3) compared to patients without CMV. Of 12 UC
patients with CMV, ten (83%) were treated for their index
flare with steroids or 6-mercaptopurine. Only one patient
Introduction
Although cytomegalovirus (CMV) infection is well recognized in immunocompromised hosts (e.g., HIV infection,
bone marrow transplant recipients) [1, 2], the reported
prevalence and pathogenicity of CMV infection in patients
with inflammatory bowel disease (IBD) are variable. CMV
infection is frequently identified in the colonic mucosa of
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Methods
Patient Population
Statistics
An Institutional Review Board waiver of consent was
obtained prior to initiating this retrospective study.
Between January 2002 and January 2006, patients who
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Results
Patient Population
During the study period, 142 patients underwent endoscopy
for indication of suspected IBD flare and had endoscopic
and histological evidence of IBD with active colitis. The
mean age was 40 13 years (Table 1); 90 (63%) were
male, and 98 (69%) were Latino. Sixty-one patients (43%)
were hospitalized at the time of endoscopy, and 68 (48%)
were newly diagnosed with IBD. One hundred twenty-two
patients (86%) had UC and 20 patients (14%) had CD. Of
the 122 patients with UC, 22 (26%) were being treated with
steroids, nine (7%) were being treated with immunemodulators, and one (1%) was being treated with biologics
at the time of endoscopy. Of the 20 patients with CD, eight
(40%) were being treated with steroids, four (20%) were
Table 1 Characteristics of patients at time of endoscopy for index
flare
Characteristic
Overall
n = 142
Ulcerative
colitis
n = 122
Crohns
disease
n = 20
40 13
40 13
39 14
Male (%)
90 (63%)
78 (64%)
12 (60%)
Latino
98 (69%)
84 (69%)
14 (70%)
19 (13%)
14 (11%)
5 (25%)
Race
Caucasian
18 (13%)
17 (14%)
1 (5%)
Asian (%)
6 (4%)
6 (5%)
0 (0%)
1 (1%)
68 (48%)
1 (1%)
61 (50%)
0 (0%)
7 (35%)
Hospitalization (%)
61 (43%)
51 (42%)
10 (50%)
5-ASA (%)
52 (37%)
46 (38%)
6 (30%)
Steroids (%)
30 (21%)
22 (18%)
8 (40%)
6-MP/AZA/MTX (%)
12 (8%)
9 (7%)
3 (15%)
Anti-TNF (%)
3 (2%)
1 (1%)
2 (10%)
Medications
UC
CD
N=122
N=20
CMV+
CMV-
CMV+
CMV-
N=12
N=110
N=0
N=20
Fig. 1 Flow chart of 142 consecutive patients undergoing colonoscopy or sigmoidoscopy for acute inflammatory bowel disease (IBD)
colitis flare
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Table 2 Baseline clinical, biochemical and endoscopic characteristics of patients with ulcerative colitis flare related to cytomegalovirus
(CMV) status
Characteristic
CMV?
n = 12
CMVn = 110
OR
(95% CI)
5 (42%)
54 (49%)
0.7 (0.22.5)
Male
New diagnosis
9 (75%)
5 (42%)
69 (63%)
56 (51%)
1.8 (0.57.0)
0.7 (0.22.3)
Steroids
4 (33%)
18 (16%)
2.6 (0.79.4)
6MP/AZA
1 (8%)
8 (7%)
1.4 (0.211.9)
Anti-TNF
0 (0%)
1 (1%)
1.0 (1.01.0)
Oral/topical 5-ASA
7 (58%)
40 (36%)
2.5 (0.88.6)
WBC [10,300/mm3
7 (58%)
23 (21%)
5.3 (1.518.2)
1.4 (0.45.0)
4 (33%)
29 (26%)
6 (50%)
30 (27%)
2.7 (0.88.9)
6 (50%)
32 (27%)
2.7 (0.88.9)
Distal colitis
1 (8%)
42 (38%)
0.2 (0.01.2)
Left-sided colitis
7 (58%)
35 (32%)
3.0 (0.93.2)
Pancolitits
4 (33%)
33 (30%)
1.2 (0.34.1)
Hospitalization required
9 (75%)
42 (38%)
4.9 (1.219.0)
Hospitalization [7 days
5 (42%)
12 (11%)
5.0 (1.621.3)
Discussion
The role of CMV in active IBD has been controversial.
Early studies have highlighted the association of CMV
infection with severe active IBD and high doses of
immunosuppressive medications. Initial studies reported
CMV inclusion bodies in colectomy specimens with fulminant or steroid-refractory UC [8, 15, 16]. In addition,
treatment with steroids [17], cyclosporine [18], anti-TNF
agents [19], and leukapharesis [20] has been associated
with an increased risk of CMV infection. However, other
studies have challenged the pathogenicity of CMV in
active IBD by demonstrating a lack of correlation of
CMV and clinical severity of IBD [21]. Based on the
association of CMV with severe steroid-refractory IBD,
one can hypothesize that CMV plays a role in flares of IBD,
either by causing CMV colitis directly or by exacerbating
underlying IBD. However, it is also possible that
CMV may be an innocent bystander detected in the
Table 3 Summary of the 12 ulcerative colitis patients with cytomegalovirus (CMV) infection
Patient
Age/
gender
Duration of
UC (years)
Medication
Endoscopic
involvement
Treatment
Length of
stay (days)
Days to subsequent
hospitalization
Follow-up
(months)
65/M
8.0
29/M
0.2
5-ASA, 6MP
Left-sided
5-ASA, 6-MP
Not hospitalized
13.6
5-ASA, S
Distal
S, 5-ASA
24
Not hospitalized
32/M
14.2
5.0
5-ASA, S
Left-sided
S, 5-ASA
14
Not hospitalized
52.4
19/M
None
Left-sided
5-ASA
15
41.0
53/M
0.5
5-ASA, S
Left-sided
S, 5-ASA
104
49.4
30/F
0.8
5-ASA
Pancolitis
S, 5-ASA
18
9.9
33/M
None
Pancolitis
S, 5-ASA
18
Not hospitalized
46.1
34/M
0.4
5-ASA, S
Left-sided
5-ASA, S
Not hospitalized
14.5
43/F
None
Pancolitis
S, 5-ASA
32.0
10
57/M
None
Pancolitis
S, 5-ASA
Not hospitalized
0.3
11
12
33/M
40/F
2.0
0
5-ASA
None
Left-sided
Left-sided
S, 5-ASA
5-ASA
5
5
Not hospitalized
25
0.2
2.9
UC ulcerative colitis, M male, F female, 5-ASA 5-aminosalicylic acid, 6-MP 6-Mercaptopurine, S steroid
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Fig. 2 KaplanMeier estimates of ulcerative colitis-related hospitalization rates for patients with CMV infection (n = 12) and without
CMV infection (n = 110)
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