close

Вход

Забыли?

вход по аккаунту

?

High Frequency of Silent Inflammatory Bowel Disease in Spondylarthropathy.

код для вставкиСкачать
ARTHRITIS & RHEUMATISM Volume 37
Number 1, January 1994, pp 23-31
0 1994, American College of Rheumatology
23
HIGH FREQUENCY OF
SILENT INFLAMMATORY BOWEL DISEASE
IN SPONDYLARTHROPATHY
MARJATTA LEIRISALO-REPO, ULLA TURUNEN, SVANTE STENMAN,
PETRI HELENIUS, and KARI SEPPALA
Objective. To search for an association between gut
infection, gut inflammation, and spondylarthropathies.
Methods. Ileocolonoscopy was performed in 118
patients with various inflammatory and noninflammatory joint diseases and in 24 patients with uncomplicated
acute bacterial gastroenteritis.
Results. Endoscopic lesions were more frequent
in patients with spondylarthropathy (44%) compared
with those with other inflammatory arthritides (6%;
P = 0.001). Ileal changes were observed only in patients
with spondylarthropathy (20% versus 0%; P = 0.01).
Inflammatory bowel disease was the endoscopic diagnosis in 19% of the arthritis patients. Possible or definite
Crohn’s disease was diagnosed in 26% of patients with
chronic spondylarthropathy, and ulcerative colitis in 1
patient with rheumatoid arthritis and in 1 with chronic
uroarthritis. Histologic evidence of inflammation differed less distinctly than endoscopy findings between
patient groups. There was no association of gut lesions
with the use of nonsteroidal antiinflammatory drugs or
with the presence of HLA-B27.
Conclusion. Gut inflammation is frequent in paPresented in part at the 55th Annual Scientific Meeting of
the American College of Rheumatology, Boston, MA, November
17-21, 1991.
From the Second Department of Medicine, Helsinki University Central Hospital, and Department of Pathology, University
of Helsinki, Helsinki, Finland.
Supported by the Nanna Svartz grant, and by grants from
the Finnish Cultural Fund, the Yrjo Jahnsson Foundation, and the
Rheumatism Research Foundation, Finland.
Majatta Leirisalo-Repo, MD; Ulla Turunen, MD; Svante
Stenman, MD; Petri Helenius, MD; Kari Seppala, MD.
Address reprint requests to Marjatta Leirisalo-Repo, MD,
Second Department of Medicine, Helsinki University Central Hospital, SF-00290 Helsinki, Finland.
Submitted for publication December 9, 1992; accepted in
revised form June 14, 1993.
tients with spondylarthropathy, and one-fourth of the
patients who have chronic disease have early features of
Crohn’s disease.
Spondylarthropathy is a term used to describe a
group of patients with seronegative arthropathies and
with a high frequency of HLA-B27 (1). The spectrum
of the spondylarthropathies varies from acute transient arthritides to chronic diseases. Bacterial infection is linked to the development of some forms of
spondylarthropathy, the clearest example of which is
reactive arthritis. In other cases, the role of infection is
less clear. In patients with reactive arthritis triggered
by Yersinia or Salmonella infections, high-level and
persistent IgA-class antibodies and secretory IgAclass antibodies (2,3) can indicate impaired elimination
of the microbe and persistence of antigen in the region
of the mucosal immune system of the gut. Ten years
after the acute episode, one-third of the patients with
reactive arthritis have sacroiliitis (4), and 20 years
later, even frank ankylosing spondylitis can occur (5).
Factors contributing to the development of chronic
spondylarthropathy are not completely known, but
persistent infection or a chronic focus of inflammation
are good candidates.
It has been suggested that gastrointestinal infection also plays a role in the exacerbation of chronic
ankylosing spondylitis (6). A high IgA antibody response (7) and depressed cellular response to Klebsiella (8,9) and a cytotoxic T cell response to HLAB27 positive peripheral blood mononuclear cells
modified by Klebsiella culture filtrate (10) also favor
the role of gut bacteria as triggering or modifying
factors in the development of ankylosing spondylitis.
About 4% of patients with ankylosing spondy-
24
LEIRISALO-REP0 ET AL
Table 1. Characteristics of the 142 study patients, by diagnostic group*
Reactive arthritis
Sacroiliitisl
Acute
Low
bacterial
Chronic oligol ankylosing Rheumatoid
Acute Chronic Acute Chronic polyarthritis spondylitis
arthritis
back pain Miscellaneous gastroenteritis
(n = 16)
(n = 37)
(n = 11)
(n = 4)
(n = 18)
(n = 24)
(n = 13) (n = 5) (n = 3) (n = 11)
Enteroarthritis
Menlwomen
HLA-B27+
Peripheral
arthritis
Enthesopathy
Sacroiliac
pain
Abdominal
symptoms
NSAID
treatment
Uroarthritis
419
11/13
13
213
415
2
310
313
3
813
9/10
10
2
3
4
2
4
2
1
7
11
4
1
11
5
3
4/12
7/15
15
25/12
33/33
16
318
218
11
014
1I4
0
4/14
6/14
8
12/12
015
0
1
1
9
32
0
1
0
1
1
1
2
7
6
20
7
1
7
24
9
13
30
10
3
9
0
0
* Patients with chronic reactive arthritis had a duration of arthritis 2 6 months. HLA-B27 values are the number positive/total number tested.
The miscellaneous rheumatic diseases were psoriatic arthritis (4 patients), systemic lupus erythematosus or other systemic collagenosis (4
patients), arthralgidfibromyalgia syndromes (6 patients), acute arthritis triggered by preceding streptococcal pharyngitis (2 patients), chronic
intis (1 patient), and sarcoidosis (1 patient). NSAID = nonsteroidal antiinflammatory drug.
litis, evaluated by radiology and sigmoidoscopy, have
ulcerative colitis or Crohn’s disease (11). However,
ileocolonoscopic studies have revealed a high frequency of inflammatory changes in the terminal ileum
and cecum in patients with prolonged or chronic
seronegative oligoarthritis and in patients with ankylosing spondylitis complicated by peripheral arthritis,
but only occasionally in those with pure axial arthritis
(12). Both acute and chronic inflammation with features
of early Crohn’s disease have been observed (13).
To study the presence of gut lesions with respect to the duration of arthritis, we performed ileocolonoscopy in patients with the whole spectrum from
acute reactive arthritis to chronic spondylarthropathies. To study the suggested role of nonsteroidal
antiinflammatory drugs (NSAIDs) in the development
of gut lesions (14), two groups of control patients
taking NSAIDs were also included: a group with
various inflammatory rheumatic diseases and a group
with noninflammatory back pain. Because enteric infections are associated with the development of reactive arthritis, we also studied patients with uncomplicated acute bacterial gastroenteritis.
PATIENTS AND METHODS
Patients. We performed ileocolonoscopies on 118
patients treated for various joint or back symptoms at the
outpatient department of Helsinki University Central Hospital. The ileocolonoscopies were performed at the Department of Gastroenterology, for a clinical indication of silent
gut inflammation. Patients with previously diagnosed inflammatory bowel disease or with chronic diarrhea were excluded from the study.
A group of 24 patients with the diagnosis of uncomplicated acute bacterial gastroenteritis was also included in
the study. Overall, there were 65 men and 77 women, with a
mean age of 35.4 years (range 17-77). The patients gave
informed consent, and the study was approved by the
hospital’s ethics committee.
The 142 patients were grouped according to clinical
diagnosis (Table 1). The 32 patients with reactive arthritis
were subgrouped into those with acute symptoms (duration
of arthritis <6 months) and those with chronic symptoms
(duration of arthritis 2 6 months). The triggering infections
are presented in Table 2. The 11 patients with rheumatoid
arthritis had definite or classic disease, according to the
American College of Rheumatology (formerly, the American
Rheumatism Association) criteria (15). Four patients had
noninflammatory low back pain. A group of 18 patients had
miscellaneous rheumatic diseases (4 had psoriatic arthritis, 4
systemic lupus erythematosus or other systemic collagenosis, 6 arthralgidfibromyalgia syndromes, 2 acute arthritis
triggered by preceding streptococcal pharyngitis, 1 chronic
iritis, and 1 sarcoidosis). Twenty-four patients had culturepositive acute bacterial gastroenteritis without joint symptoms (Table 2).
We use the term “spondylarthropathy” for the reactive arthritides, seronegative chronic oligo/polyarthritis, and
sacroiliitis/ankylosing spondylitis. The term ‘‘chronic
spondylarthropathy” refers to chronic oligo/polyarthritis or
sacroiliitis/ankylosing spondylitis.
Endoscopic assessment. The ileocolonoscopy was
performed by one of us (UT or KS), using an Olympus
endoscope (Olympus, Lake Success, NY). The endoscopist
did not participate in the grouping or treatment of the
patients. Macroscopic lesions were graded &3, as follows:
25
GUT INFLAMMATION IN SPONDYLARTHROPATHY
Table 2. Bacterial etiology of the reactive arthritis and gastroenteritis
Enteroarthritis
Uroarthritis
Acute
bacterial
gastroenteritis
(n = 24)
Acute
(n = 13)
Chronic
(n = 5)
Acute
(n = 3)
Chronic
(n = 11)
6
0
3
1
0
1
1
1
3
0
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
8
1
4
1
13
0
2
0
~~
Yersinia enterocolitica
Yersinia pseudotuberculosis
Salmonella
Shigella Jexneri
Shigella sonnei
Campylobacter jejuni
Staphylococcus aureus
Diarrhea, etiology unknown
Chlamydia trachomatis
Neisseria gonorrhoeae
Nonspecific urethritis
0
0
0
grade 0 = normal, grade 1 = redness and edema of the
mucosa, grade 2 = small ulcerations of the mucosa, and
grade 3 = mucosal edema, ulcerations, and hemorrhage. In
the final analysis, grades 2 and 3 were interpreted as abnormal. The endoscopist also identified the macroscopic appearance as either acute inflammation (superficial hemorrhages, mucous edema/exudation, small superficial
ulcerations, partially visible vascularity) or chronic inflammation (large ulceration[s], scarring, and/or pseudopolyposis). Aphthoid ulcer, recognized as an early feature of
Crohn’s disease, is often preceded by patchy hyperemia,
friable mucosa, a “worm-eaten” mucosal pattern, and pinpoint hemorrhages (see ref. 16). On the basis of the macroscopic impression, the endoscopist also grouped the findings
as follows: normal, mild nonspecific inflammation, ulcerative colitis (possible or definite), Crohn’s disease (possible
or definite), or indeterminate colitis.
Histologic assessment. During endoscopy, biopsies
were taken of any macroscopic changes. The lesions were
often very small and patchy, which impaired the accuracy of
the biopsies. In addition, 4-6 biopsies of the terminal ileum
(when reached), cecum, transverse and sigmoid colon, and
rectum, even if macroscopically normal, were routinely
obtained. Tissues were fixed in formalin and embedded in
paraffin. Sections (10 pm) were stained with hematoxylin
and eosin and with periodic acid-Schiff. The histologic
features were analyzed and graded by one of us (SS), a
pathologist, who was unaware of the clinical features.
The histologic features were graded 0-3, as follows:
grade 0 = normal (low numbers of lymphocytes and plasma
cells in the lamina propria, no or few granulocytes), grade 1
= slight invasion of lymphocytes and/or plasma cells or
occasional granulocytes in the lamina propria, grade 2 =
moderate to severe inflammation, abundant lymphocytes
and/or plasma cells or granulocytes occasionally seen deep
in the mucosa, or in the muscularis, granulocyte invasion in
the epithelial layer sometimes observed, grade 3 = same as
grade 2 , but damaged or severely distorted mucosa, sometimes with ulcerations. In the final analysis, grades 2 and 3
were interpreted as abnormal.
The histologic changes were also classified as acute
0
0
0
0
0
0
0
0
2
0
1
2
4
0
0
0
0
or chronic. The inflammation was classified as acute if
granulocytes were the dominant cell population, and especially, if acute hemorrhages occurred or the epithelium was
invaded by granulocytes. The lesions were chronic if mononuclear cells dominated, and fibrotic changes were often
present.
Statistical analysis. Data were analyzed using the
BMDP software. For comparisons between patient groups,
chi-square test with Yates’ correction or Fisher’s exact test
was used. The correlation between endoscopic and histologic findings was calculated by the kappa statistic, which
measures the degree of agreement. Kappa values greater
than 0.75 are considered to represent excellent agreement,
those between 0.40 and 0.75 fair to good agreement, and
those below 0.40 poor agreement beyond chance (17).
RESULTS
Clinical symptoms. The main clinical symptoms
of the study patients are presented in Table 1, Excluding patients with acute bacterial gastroenteritis, 66% of
the patients had peripheral joint symptoms, and 54%
had some abdominal symptoms, mainly transient upper gastric pain, heartburn, or transient loose stools.
Frequency of endoscopic lesions. Except for patients with acute gastroenteritis, the endoscopic lesions observed were, in most cases, small and few,
surrounded by normal mucosa. Changes were observed in 44% of the patients with spondylarthropathy,
more often in the colon (39%) than in the terminal
ileum (20%). Only in patients with chronic uroarthritis
were lesions observed less frequently (Table 3). Enteroarthritis patients had both ileal and colonic
changes, while uroarthritis patients had only colonic
changes (Figure 1). The high frequency of endoscopic
lesions in the spondylarthropathy group (44%) is in
LEIRISALO-REP0 ET AL
26
Table 3. Inflammatory changes noted during ileocolonoscopy in the 142 study patients, by diagnostic group*
Reactive arthritis
Enteroarthritis
Uroarthritis
Acute Chronic Acute Chronic
(n = 13) (n = 5) (n = 3) (n = 11)
Inflammation
By endoscopy
In ileum
In colon
By histology
In ileum
In colon
By endoscopy or
histology
In ileum
In colon
Chronic oligol
polyarthritk
(n = 16)
Sacroiliitisi
Acute
ankylosing Rheumatoid
Low
bacterial
spondyliti arthritis back pain Miscellaneous gastroenteritis
(n = 37)
(n = 11)
(n = 4)
(n = 18)
(n = 24)
7/13
3/13
5/13
5/13
3/13
3/13
7/13
215
013
215
115
013
115
315
213
013
213
213
212
013
313
2/11
0110
2/11
3/11
2/10
1/11
4/11
6/16
3111
6/16
5/16
511 1
0116
9/16
18/37
9/34
16/37
15/37
8/34
13/37
23/37
2111
019
2111
6111
319
311I
711I
014
013
014
1I 4
113
014
I 14
0118
2/17
3/18
5/18
2 1124
319
20124
18/24
1I8
17/24
23/24
3/13
5/13
013
315
213
213
2/10
2/11
7111
6/16
14/35
20137
319
411 1
1I3
014
2/17
3/18
319
22/24
* Values are the number positiveltotal
0117
0118
5/18
number tested. See Table I for other details.
contrast to the low frequency of such lesions in the
control patients with inflammatory arthritis (6%; P =
0.001). Endoscopic lesions of the gut were more
frequent in patients with spondylarthropathies than in
those with other inflammatory arthritides, both in the
ileum (20% versus 0%; P = 0.01) and in the colon (39%
versus 6%; P = 0.003).
Among patients with chronic spondylarthropathy, endoscopic inflammation was more frequent in
those with only axial involvement compared with
those with peripheral arthritis (64% versus 32%; P =
0.048). This was mainly due to the higher frequency of
colonic lesions (59% versus 29%; P = 0.057). There
was no statistically significant difference in the frequency of ileal changes.
Acute lesions were most frequent in patients
with acute bacterial gastroenteritis, and their frequency decreased with increasing duration of arthritis
(Figure 2). With chronic inflammatory lesions the
reverse was observed; the frequency increased with
the duration of arthritis (Figure 2).
In 2 patients with acute bacterial gastroenteritis
(8%) and in 1 patient with acute (8%) and 1 with
chronic (20%) enteroarthritis, the endoscopic appearance of the inflammatory lesions in the gut was severe
enough to warrant the diagnosis of possible Crohn's
100
z
w
u)
2
0
3 "
8
5 "
n
Figure 1. Frequency of ileocolonoscopic lesions in different patient
groups, in the ileum (B), the colon (B), and both the ileum and colon
(a).Open bars indicate normal endoscopic findings.
Figure 2. Frequency of acute (H) and chronic (El) endoscopic
lesions in different patient groups. Open bars indicate normal
endoscopic findings.
GUT INFLAMMATION IN SPONDYLARTHROPATHY
Figure 3. Frequency of endoscopic lesions, grouped as possible
Crohn’s disease (M),definite Crohn’s disease (B),and other inflammatory changes (El). The latter group includes possible ulcerative
colitis (2 patients with acute enteritis), definite ulcerative colitis (1
patient with chronic uroarthritis, 1 patient with rheumatoid arthritis), and indeterminate colitis (1 patient with ankylosing spondylitis).
Open bars indicate normal endoscopic findings.
disease (Figure 3). These 4 patients had Yersiniu
enterocoliticu infection. Crohn’s disease was diagnosed in 26% of patients with chronic spondylarthropathy (possible Crohn’s disease in 13% and definite
Crohn’s disease in 13%). In addition, ulcerative colitis
was diagnosed in 1 patient with rheumatoid arthritis
and in 1 with chronic uroarthritis, and indeterminate
colitis in 1 patient with ankylosing spondylitis.
Results of bacterial cultures of biopsy samples. In
63% of the patients, biopsies of the gut were cultured
for the presence of enteric pathogens. The cultures
were all negative in all patient groups, except for 18 of
the 22 patients with acute bacterial gastroenteritis
whose tissues were cultured.
Results of histologic examination of biopsy samples. Histologic changes were frequent in all disease
groups, with the highest frequency in patients with
acute bacterial gastroenteritis (Figure 4). The differences in the frequency of changes between patients
with spondylarthropathy (37%) and those with other
forms of arthritis (25-55%) were not statistically significantly different. Acute inflammation was most frequent in patients with acute bacterial gastroenteritis,
while chronic lesions occurred in all patient groups
(Table 4).
In patients with spondylarthropathies, inflammatory changes were as frequent in the ileum (27%) as
in the colon (21%). In those with chronic spondylarthropathy, histologic inflammation was as frequent in
27
those with only axial involvement (41%) as in those
with peripheral involvement (36%).
There was good agreement between endoscopic
and histologic evidence of hcute lesions ( K = 0.425),
but the correlation between chronic changes was poor
( K = 0.197). Endoscopic evidence of inflammation in
the ileum and in the colon was poorly correlated with
the respective histologic changes: 55% had normal
findings both by endoscopy and by histology, and 15%
had inflammation by both techniques ( K = 0.325). The
ileum was normal by both criteria in 61% of the
patients, while 10% of patients had an inflamed ileum
by both criteria ( K = 0.212).
Fifty-six percent of the patients with enteroarthritis and 60% of those with chronic spondylarthropathy had endoscopic or histologic evidence of gut
inflammation, frequencies that are comparable to the
64% in patients with rheumatoid arthritis (Table 3).
The frequency of inflammation was lower (36%) in
patients with chronic uroarthritis, which is similar to
the 27% frequency in the control groups (patients with
low back pain and miscellaneous rheumatic diseases).
Of patients with acute bacterial gastroenteritis, 96%
had either endoscopic or histologic evidence of gut
inflammation.
Association between gut lesions and HLA-B27.
The frequency of endoscopic and histologic lesions did
not differ significantly between HLA-B27 positive and
negative arthritis patients (Table 5).
Association between gut lesions and the use of
NSAIDs. Patients who had used NSAIDs within the
preceding month had slightly more frequent endo-
Figure 4. Frequency of histologic changes in different patient
groups, in the ileum (M),the colon (Ed), and both the ileum and colon
(B). Open bars indicate normal histologic findings.
LEIRISALO-REP0 ET AL
28
Table 4. Number (%) of patients with acute and chronic lesions on histologic examination of gut
biopsy tissues*
~~
Reactive arthritis
Lesion
type
Acute
= 16)
(n
Chronic
(n = 16)
Chronic
spondylarthropathy
(n = 53)
Rheumatoid arthritis
+ miscellaneous
(n = 29)
Acute
bacterial
gastroenteritis
(n = 24)
* Patients with chronic spondylarthropathy had oligo/polyarthritisor sacroiliitidankylosing spondylitis. See Table 1 for other details.
scopic lesions (37%) than did those without such a
history (20%), but the difference was not statistically
significant. A similar trend in the endoscopic lesions
was observed both in the ileum (18% versus 4%) and in
the colon (32% versus 20%). The frequencies of histologic changes were much the same (37% versus 32%),
both in the ileum (27% versus 22%) and in the colon
(20% in both groups).
DISCUSSION
We observed endoscopic lesions in the gut in
44% of patients with spondylarthopathies; a figure
much higher than that observed in patients with rheumatoid arthritis or with other joint symptoms. Our
results are comparable to those of previous studies in
which macroscopic inflammatory lesions were described in one-third and histologic idammation in twothirds of patients with chronic spondylarthropathy (18).
An even higher frequency has been reported in patients
with oligoarticularjuvenile chronic arthritis (19).
Transient peripheral oligoarthritis occurs in
about 20% and ankylosing spondylitis in 4 7 % of
patients with chronic inflammatory bowel disease
(20,21), especially in those with colitis (20). In patients
with ankylosing spondylitis, inflammatory bowel disTable 5. Frequency of gut inflammation in patients with musculoskeletal symptoms, according to HLA-B27 positivity*
Inflammation site
By endoscopy
Ileum
Colon
Ileum or colon
By histology
Ileum
Colon
Ileum or colon
HLA-B27+
HLA-B27-
17
30
34
8
28
28
25
24
34
29
10
35
* Values are percentages. None of the differences were significant.
ease has been reported to occur in only about 5-10% of
the patients studied by conventional techniques such
as sigmoidoscopy and radiology (1 1,22). In the present
study, a much higher frequency (27%)of inflammatory
bowel disease, mainly with features of Crohn’s disease, was diagnosed by endoscopy in the patients with
chronic spondylarthropathy . This prevalence of inflammatory bowel disease in spondylarthropathy is
much higher than in asymptomatic subjects in population screening programs (23). Long-term followup of
these patients is necessary, so that the prognostic
significance of these findings can be determined.
Chronic inflammatory bowel disease has been noted in
15 of these patients (unpublished observations).
Inflammation in the colon was as frequent as in
the ileum. The frequency of ileal changes was lower
than in the studies reported by Mielants and coworkers (18,24), but comparable to the 29% reported by
Grillet et a1 (25). Lower values have been reported by
others (26,27). Colonic changes have either received
less attention (12,25,27) or the changes have been less
frequent than in ileum (13,26). Contrary to the findings
of previous studies (18,25), endoscopic lesions of the
colon were also present in a few patients with uroarthritis. One patient with chronic uroarthritis developed ulcerative colitis, a rare association that has been
described previously (28,29).
Various frequencies of chronic inflammatory
changes in histologic samples have been observed in
patients with spondylarthropathies (18,25,26). In our
study, histologic changes were frequent in those patients, but such changes were also observed in our
appropriately chosen control patients. Most of the
control patients had inflammatory or autoimmune diseases. In such patients, chronic histologic inflammation can be part of the autoimmune disease (30), but
such lesions are not associated with clinical inflammatory bowel disease. A high frequency of histologic
GUT INFLAMMATION IN SPONDYLARTHROPATHY
inflammation was also observed by Dougados et a1
(27), both in patients with chronic spondylarthropathy
and in nonarthritic controls.
The discrepancy in the histologic findings between the present study and that by De Vos, Mielants,
and coworkers (see ref. 18) is probably explained by
differences in the selection of patients. Our patients
with reactive arthritis had a shorter duration of symptoms than those described by Mielants et a1 (31). The
triggering infection was identified in most of our patients, while most of the patients studied by Mielants
et a1 had an idiopathic form of disease. The assessment
of mild inflammation in gut biopsy tissues is known to
be difficult (32). In the ileum, normal lymphatic structures in technically damaged and distorted tissue samples are easily misinterpreted as having inflammation.
Mononuclear cells, which are normally present in the
ileum, complicate the diagnosis of chronic ileitis. Also,
the patchy nature of lesions can contribute to the
difficulty in focusing the biopsy at the proper site. The
good correlation between endoscopic and histologic
features in patients with uncomplicated acute bacterial
gastroenteritis supports the accuracy of the histologic
evaluation. Inflammation in these cases was acute and
affected large areas of the mucosa.
Increased gut permeability and inflammation
have been associated with the use of NSAIDs
(14,33,34). However, in patients with ankylosing spondylitis, other spondylarthropathies, or rheumatoid
arthritis, increased gut permeability has also been
described in those not taking NSAIDs (35,36). Consistent with the findings of previous studies (26,37), we
observed no association between the use of NSAIDs
and endoscopic evidence of lesions. The localization
of gut lesions in patients with NSAID-induced enteropathy is also different from that in patients with
spondylarthropathy : NSAID-induced lesions occur in
the mid-small intestine, rather than in the terminal
ileum or colon (38). Furthermore, endoscopic lesions
characteristic of Crohn’s disease were only seen in
patients with spondylarthropathies, not in other patient groups taking NSAIDs.
Colon involvement is a common feature of the
infections known to trigger reactive arthritis (39).
Salmonella (40) and Campylobacter (41,42) can cause
a colitis resembling Crohn’s disease or ulcerative
colitis. In addition, patients with Yersinia enteritis can
have edema, lymphoid hyperplasia, and even ulcerations or aphthous changes in the terminal ileum or
proximal colon, features mimicking those of Crohn’s
29
disease (4346). Such lesions were also observed in the
present study. We suggest that Yersinia infection
should be excluded in patients with terminal ileitis
detected at endoscopy. With Yersinia infection, the
changes in the terminal ileum are transient, and according to radiologic studies, heal within 3 months
(47). However, in one of our patients with chronic
enteroarthritis triggered by Y enterocolitica, the terminal ileitis progressed to chronic Crohn’s disease.
Because we also included patients with bacterial gastroenteritis not complicated by arthritis, we
were able to compare the role of infection in the
development of gut inflammation. The lesions in patients with acute enteroarthritis were similar to those
in patients with acute enteritis, except for the extent of
the lesions. In patients with infectious enteritis, the
inflammation was evenly distributed, while in patients
with arthritis, the lesions were patchy and few.
The chronic infectioushnflammatory gut lesions
can allow bacterial antigens from the gut to enter the
circulation. Antigenemia may stimulate both immunologic and nonimmunologic inflammatory mechanisms,
and thereby lead to the development of chronic arthritis, sacroiliitis, and ankylosing spondylitis. This is
consistent with studies showing increased mucosal
permeability in patients with Yersinia enteritis (48,49),
ankylosing spondylitis (50), or Crohn’s disease (51), as
well as with the raised serum levels of endotoxin in
patients with chronic spondylarthropathy , rheumatoid
arthritis, or Crohn’s disease (52). The role of gut
inflammatiodincreased mucosal permeability is probably also reflected in the raised IgA class antiklebsiella antibodies in patients with ankylosing spondylitis (533) and in those with inflammatory bowel
disease (53).
In conclusion, early changes of Crohn’s disease
are clearly more frequent in patients with spondylarthropathy than in other arthritis patients. Patients with
chronic spondylarthropathy have the highest risk. It
can be speculated that the occurrence of gut inflammation and joint inflammation was coincidental or that
the inflammatory diseases may have been triggered by
the same etiologic agent(s).
REFERENCES
1. Dougados M, van der Linden S, Juhlin R, Huitfeldt B, Amor B,
Calin A, Cats A, Dijkmans B, Olivieri I, Pasero G , Veys E,
Zeidler H, The European Spondylarthropathy Study Group:
The European Spondylarthropathy Study Group preliminary
30
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
LEIRISALO-REP0 ET AL
criteria for the classification of spondylarthropathy. Arthritis
Rheum 34:1218-1227, 1991
Granfors K, Toivanen A: IgA-anti-yersinia antibodies in yersinia triggered reactive arthritis. Ann Rheum Dis 45561-565,
1986
Maki-Ikola 0, Leirisalo-Rep0 M, Kantele A, Toivanen P,
Granfors K: Salmonella-specific antibodies in reactive arthritis.
J Infect Dis 164:1141-1 148, 1991
Leirisalo M, Skylv G, Kousa M, Voipio-Pulkki L-M, Suoranta
H, Nissila M, Hvidman L, Damm Nielsen E, Svejgaard A,
Tiilikainen A, Laitinen 0: Followup study on patients with
Reiter’s disease and reactive arthritis, with special reference to
HLA-B27. Arthritis Rheum 25:249-259, 1982
Sairanen E, Paronen I, Mahonen H: Reiter’s syndrome: a
follow-up study. Acta Med Scand 1855743, 1969
Ebringer RW, Cawdell DR, Cowling P, Ebringer A: Sequential
studies in ankylosing spondylitis: association of Klebsiella
pneumoniae with active disease. Ann Rheum Dis 37:146151,
1978
Trull A, Ebringer R, Panayi GS, Colthorpe D, James DCO,
Ebringer A: IgA antibodies in ankylosing spondylitis. Scand J
Rheumatol 12:249-253, 1983
Geczy AF, Alexander K, Bashir HV, Edmonds JP, Upfold L,
Sullivan J: HLA-B27, Klebsiella, and ankylosing spondylitis:
biological and chemical studies. Immunol Rev 70:23-50, 1983
Sheldon PJ, Pel1 PA: Lymphocyte proliferative responses to
bacterial antigens in B27-associated arthropathies. Br J Rheumatol 24: 11-18, 1985
Geczy AF, McGuigan LE, Sullivan JS, Edmonds JP: Cytotoxic
T lymphocytes against disease associated determinant(s) in
ankylosing spondylitis. J Exp Med 164:932-937, 1986
Meuwissen SGM, Dekker-Saeys BJ, Agenant D, Tytgat GNJ:
Ankylosing spondylitis and inflammatory bowel disease. I.
Prevalence of inflammatory bowel disease in patients suffering
from ankylosing spondylitis. Ann Rheum Dis 37:3&32, 1978
Mielants H, Veys EM, Cuvelier C, De Vos M, Botelberghe L:
HLA-B27 related arthritis and bowel inflammation. 11. Ileocolonoscopy and bowel histology in patients with HLA-B27 related arthritis. J Rheumatol 12:29&298, 1985
Cuvelier C, Barbatis C, Mielants H, De Vos M, Roels H, Veys
E: Histopathology of intestinal inflammation related to reactive
arthritis. Gut 1928:394-401, 1987
Bjarnason I, Williams P, So A, Zanelli GD, Levi JA, Gumpel
JM, Peters TJ, Ansell B: Intestinal permeability and inflammation in rheumatoid arthritis: effects of non-steroidal antiinflammatory drugs. Lancet 2:1171-1174, 1984
Ropes MW, Bennett GA, Cobb S, Jacox R, Jessar RA: 1958
revision of diagnostic criteria for rheumatoid arthritis. Bull
Rheum Dis 9:175-176, 1958
Sankey EA, Dhillon AP, Anthony A, Wakefield AJ, Sim R,
More L, Hudson M, Sawyerr AM, Pounder RE: Early mucosal
changes in Crohn’s disease. Gut 34:375-381, 1993
Fleiss JL: Statistical Methods for Rates and Proportions. Second edition. New York, Wiley, 1981
De Vos M, Cuvelier C, Mielants H, Veys E, Barbier F, Elewaut
A: Ileo-colonoscopy in seronegative spondylarthropathy. Gastroenterology 96:339-344, 1989
Mielants H, Veys EM, Joos R, Cuvelier C, De Vos M, Proot F:
Late onset pauciarticular juvenile chronic arthritis: relation to
gut inflammation. J Rheumatol 143459465, 1987
Greenstein AJ, Janowitz HD, Sachar DB: The extra-intestinal
complications of Crohn’s disease and ulcerative colitis: a study
of 700 patients. Medicine (Baltimore) 55:401412, 1976
Haslock I, Wright V: The musculo-skeletal complications of
Crohn’s disease. Medicine (Baltimore) 52:217-225, 1973
Costello PB, Alea JA, Kennedy AC, McCluskey RT, Green FA:
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
38.
39.
40.
41.
42.
Prevalence of occult inflammatory bowel disease in ankylosing
spondylitis. Ann Rheum Dis 39:453456, 1980
Mayberry JF, Ballantyne KC,Hardcastle JD, Mangham C, Pye
G: Epidemiological study of asymptomatic inflammatory bowel
disease: the identification of cases during a screening programme for colorectal cancer. Gut 30:481483, 1989
Mielants H, Veys EM, Joos R, Noens L, Cuvelier C, De Vos M:
HLA antigens in seronegative spondylarthropathies, reactive
arthritis and arthritis in ankylosing spondylitis: relation to gut
inflammation. J Rheumatol 14:466-471, 1987
Grillet B, de Clerck L, Dequeker J, Rutgeerts P, Geboes K:
Systematic ileocolonoscopy and bowel biopsy study in spondylarthropathy. Br J Rheumatol 26338-340, 1987
Simenon G, van Gossum A, Adler M, Rickaert F, Appelboom
T: Macroscopic and microscopic gut lesions in seronegative
spondylarthropathies. J Rheumatol 17: 1491-1494, 1990
Dougados M, Alemanni M, Tulliez M, Abadia R, Kahan A,
Delrieu F, Awada H, Christoforov B, Amor B: Ilkocolonoscopie systkmatique au cours des spondylarthropathies seronkgatives. Rev Rhum Ma1 Osteoartic 54:279-283, 1987
Bourel M, Pawlotzky Y, Lenoir P, Simon M: Rectocolite
ulckro-hkmorrhagique et syndrome de Fiessinger-Leroy-Reiter
avec cellules a inclusion. Semin Hop Paris 41:1005-1008, 1968
Hickling P, Martin MFR, Brooks S: A case of Reiter’s disease
complicated by fulminating colitis. Ann Rheum Dis 41: 189-191,
1982
Siurala M, Julkunen H, Toivonen S, Pelkonen R, Saxen E,
Pitkanen E: Digestive tract in collagen diseases. Acta Med
Scand 78:13-25, 1965
Mielants H, Veys EM, Goemaere S, Goethals K, Cuvelier C,
De Vos M: Gut inflammation in the spondylarthropathies:
clinical, radiologic, biologic and genetic features in relation to
the type of histology: a prospective study. J Rheumatol 18:15421551, 1991
Seldenrijk CA, Morson BC, Meuwissen SGM, Schipper NW,
Lindeman J, Meijer MCJL: Histopathologic evaluation of colonic mucosal biopsy specimens in chronic inflammatory bowel
disease: diagnostic implications. Gut 32: 1514-1520, 1991
Auer 10, Habscheid W, Hiller S, Gerhards W, Eilles C:
Nicht-steroidale Antiphlogistika erhohen die Darmpermeabilitat. Dtsch Med Wochenschr 112:1032-1037, 1987
Morris AJ, Howden CW, Robertson C, Duncan A, Torley H,
Sturrock RD, Russell RI: Increased intestinal permeability in
ankylosing spondylitis: primary lesion or drug effect? Gut
32:1470-1472, 1991
Wendling D, Bidet A, Guidet M: Intestinal permeability in
ankylosing spondylitis. J Rheumatol 17: 114, 1990
Mielants H, Goemaere S, De Vos M, Schelstraete K, Goethals
K, Maertens M, Ackerman C, Veys EM: Intestinal mucosal
permeability in inflammatory rheumatic diseases. I. Role of
antiinflammatory drugs. J Rheumatol 18:389-393, 1991
Mielants H, Veys EM, Cuvelier C, De Vos M: Subclinical
involvement of the gut in undifferentiated spondylarthropathies.
Clin Exp Rheumatol 73499-504, 1989
Rooney PJ, Bjarnason I: NSAID gastropathy: not just a pain in
the gut! J Rheumatol 18:796978, 1991
World Health Organization Scientific Working Group: Enteric
infections due to Campylobacter, Yersinia, Salmonella, and
Shigella. Bull World Health Organ 58:519-537, 1980
Vender RJ, Marignani P: Salmonella colitis presenting as a
segmental colitis resembling Crohn’s disease. Dig Dis Sci 28:
848-851, 1983
Price AB, Jewkes J, Sanderson PJ: Acute diarrhoea: Campylobacter colitis and the role of rectal biopsy. J Clin Pathol
32:990-997, 1979
Vesterby A, Baandrup U,Jacobsen NO, Albertsen K: Campy-
GUT INFLAMMATION IN SPONDYLARTHROPATHY
lobacter enterocolitis: an important differential diagnosis in
ulcerative colitis. Acta Pathol Microbiol Immunol Scand Sect A
91:31-33, 1983
43. Antalik J: Besteht ein Zusammenhang zwischen Infektionen mit
Yersinia enterocolitica und der regionalen Enteritis? Fortschr
Rontgenstr 125510-514, 1976
44. Lingg G, Hering L, Tanneberger D: Ileitis durch Yersinia
enterocolitica: Rontgendifferentialdiagnose des Morbus Crohn.
Rontgen BI 34:447450, 1981
45. Gleason TH, Patterson SD: The pathology of Yersinia enterocolitica ileocolitis. Am J Surg Pathol 6:347-355, 1982
46. Simmonds SD, Noble MA, Freeman HJ: Gastrointestinal features of culture-positive Yersinia enterocolitica infection. Gastroenterology 92: 112-1 17, 1987
47. Ekberg 0, Sjostrom B, Brahme F: Radiological findings in
yersinia ileitis. Radiology 123: 15-19, 1977
48. Serrander R, Magnusson K-E, Kihlstrom E, Sundqvist T: Acute
yersinia infections in man increase intestinal permeability for
low-molecular weight polyethylene glycols (PEG 400). Scand J
Infect Dis 18:409413, 1986
31
49. Lahesmaa-Rantala R, Magnusson K-E, Granfors K, Leino R,
Sundqvist T, Toivanen A: Intestinal permeability in patients
with yersinia triggered reactive arthritis. Ann Rheum Dis 50:9194, 1991
50. Smith MD, Gibson RA, Brooks PM: Abnormal bowel permeability in ankylosing spondylitis and rheumatoid arthritis. J
Rheumatol 12:299-305, 1985
51. Hollander D, Vadheim CM, Brettholz E, Petersen GM,
Delahunty T, Rotter JI: Increased intestinal permeability in
patients with Crohn’s disease and their relatives: a possible
etiologic factor. Ann Intern Med lOk883-885, 1986
52. Busch J, Hammer M, Brunkhorst R, Wagener P: Endotoxinbestimmung bei entziindlich-rheumatischen Erkrankungen:
der Einfluss nichtsteroidale Antiphlogistika auf die Darmpermeabilitat. Z Rheumatol47: 156-160, 1988
53. Cooper R, Fraser SM, Sturrock RD, Gemmell CG: Raised titres
of anti-klebsiella IgA in ankylosing spondylitis, rheumatoid
arthritis, and inflammatory bowel disease. Br Med J 296:14321434. 1988
Документ
Категория
Без категории
Просмотров
0
Размер файла
896 Кб
Теги
spondylarthropathy, silent, bowen, high, inflammatory, frequency, disease
1/--страниц
Пожаловаться на содержимое документа