0016-5107/90/3606-0583$02.00/0 GASTROINTESTINAL ENDOSCOPY Copyright © 1990 by the American Society for Gastrointestinal Endoscopy
Endoscopic findings in Yersinia enterocolitica enterocolitis Takayuki Matsumoto, MD, Mitsuo Iida, Toshiyuki Matsui, MD, Kiyoto Sakamoto, Tadahiko Fuchigami, MD, Yukiaki Haraguchi, Masatoshi Fujishima,
MD MD MD MD
Fukuoka and Matsuyama, Japan
The endoscopic findings in the colon and terminal ileum in eight cases of Yersinia enterocolitica enterocolitis infection were studied. The diagnosis was based on the isolation of Y. enterocolitica in the feces and/or elevated serum antibody titers to the organism. Total colonoscopy was performed between 7 and 38 days (mean, 24 days) after the onset of symptoms. In all patients, the terminal ileum was affected, followed by frequent involvement of the ileocecal valve and the cecum, and less frequently, the ascending colon. In the terminal ileum, round or oval elevations with or without ulcers were detected. Small ulcers were detected on the ileocecal valve and in the cecum. These findings were observed even 4 to 5 weeks after the onset of symptoms, suggesting a relatively long course for this disease. (Gastrointest Endosc 1990;36:583-587)
Yersinia enterocolitica is a gram-negative rod resembling non-lactose-fermenting Escherichia coli. During the 1960s and the 1970s, it became recognized as a human pathogen in many countries including Japan. 1 Clinically, it causes acute enteritis with fever in infants 2 whereas, in adolescents and adults, acute terminal ileitis with mesenteric adenitis frequently occurs, which is often misdiagnosed as acute appendicitis. 3.4 It is also known to cause erythema nodosum,5 polyarthritis,6 and septicemia.? Although many studies concerning gastrointestinal
manifestations of Y. enterocolitica have shown its clinical,8.9 radiological,IO and ultrasonic l l features precisely, little is known about the endoscopic characteristics of this infection.8.12.13 With the development of total colonoscopy, we have been able to examine eight cases of Y. enterocolitica enterocolitis endoscopically during a 9-year period.
Received February 10, 1990. For revision April 1, 1990. Accepted July 12, 1990. From the Second Department of Internal Medicine, Kyushu University, the Department of Internal Medicine, Kyushu Central Hospital and the Division of Gastroenterology, Sawara Hospital, Fukuoka, Japan, and the Matsuyama Red Cross Hospital, Matsuyama, Japan. Reprint requests: T. Matsumoto, MD, Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Maidaishi3-1-1, Higashi-ku, Fukuoka 812, Japan. VOLUME 36, NO.6, 1990
PATIENTS AND METHODS
During the past 9 years (from 1980 to 1989), we performed total colonoscopy in eight patients with enterocolitis caused by Y. enterocolitica. The diagnosis was based on the isolation of Y. enterocolitica in the feces and/or elevated serum antibody titers to this organism. In each patient, both fecal culture and serological examinations against Y. enterocolitica were performed. Fecal culture was performed by both the method described by ZenYoji and Maruyama! and a cold-enrichment technique" of 7 to 14 days. Antibody titers were measured by bacterial agglutination tests3 in patients 2, 4, 6, 7, and 8 and comple-
ment fixation tests!5 in patients 1, 3, and 5. Both of these tests were undertaken with a 0:3 antigen preparation, since this serotype of Y. enterocolitica is the most common form in Japan.! Colonoscopy, with models CF-lOL, CF-20I, or CFV-10I (Olympus Corporation, Tokyo, Japan) for all but one patient (patient 5), for whom a PCF-lO was used, was performed between 7 and 38 days (mean, 24 days) from the onset of symptoms. In each patient, total colonoscopy was indicated because of the possibility that the patient had Crohn's ileocolitis or some other inflammatory process. Such possibilities were suggested by the results of a preceding barium followthrough or barium enema examination. RESULTS
The clinical features of the patients are summarized in Table 1. There were three male and five female 583
Table 1. Summary of patients Age (yr)
Sex
1
16
F
2
41
F
3
28
M
4
35
M
5
11
M
6
65
F
7
42
F
8
32
F
Patient
Symptoms Right lower abdominal pain Epigastric and lower abdominal pain Right lower abdominal pain; nausea Periumbilical pain; diarrhea; nausea Right lower abdominal pain; nausea Fever; low back and right knee pain Upper abdominal pain; anorexia Right lower abdominal pain; diarrhea
ESR" (mm/hr)
CRP
34
Time interval
WBC (mm")
Y. enterocolitica antibody
Y. enterocolitica culture
(3+)
9,200
(±)
(+)
7
73
(-)
4,800
(+)
(-)
13
15
(1+)
9,300
(+)
(+)
21
10
(1+)
10,300
(+)
(-)
24
6
(-)
9,500
(+)
(-)
26
72
(-)
11,200
(+)
(-)
27
42
(-)
11,900
(+)
(+)
32
30
(±)
9,600
(+)
(+)
38
(daYS)b
" ESR, erythrocyte sedimentation rate; CRP, C-reactive protein. b Time interval from the onset of symptoms until colonoscopy.
Table 2. Summary of colonoscopic findings Ascending colon
Patient
Terminal ileum
Ileocecal valve
Cecum
1
Large round or oval elevations with erosions; edema Ulcers (large and small); edema, reddened mucosa Small ulcers; small, round elevations; edema; reddened mucosa Ulcers (large and small); small, round elevations; edema; reddened mucosa Small, round elevations Ulcers (large and small); small, round elevations; edema; reddened mucosa Small ulcers; edema; small, round elevations Small, round elevations; edema; reddened mucosa
Small ulcer; swelling
Aphthoid ulcers
NP"
Small ulcer; swelling
Aphthoid ulcers
Aphthoid ulcers
Small ulcers; erosions; swelling
Aphthoid ulcers
NP
Erosions; swelling
Aphthoid ulcers
NP
NP Swelling
NP Aphthoid ulcers
NP NP
NP
NP
NP
NP
Small, round elevations
Small, round elevations
2
3
4
5 6
7
8
" NP, no particular findings.
patients. The age of the patients ranged from 11 to 65 years, with a mean of 34 years. Gastrointestinal symptoms and ileocecal tenderness were noted in all patients. In one patient (patient 6), arthropathy due to 584
Yersinia infection was suspected. There was an accelerated erythrocyte sedimentation rate in five patients, positive C-reactive protein in three patients, and leucocytosis in seven patients. Increased serum antibody GASTROINTESTINAL ENDOSCOPY
Figure 1. A, Endoscopic view of the terminal ileum in patient
1; multiple round or oval elevations with erosions can be seen. B, Endoscopic view of the terminal ileum in patient 2; large, shallow, irregular-shaped ulcers can be seen. C, Endoscopic view of the terminal ileum in patient 4; multiple small ulcers and a few round elevations can be seen. D, Endoscopic view of the ileocecal valve in patient 1; small ulcers can be seen.
titers to Y. enterocolitica serotype 0:3 were detected in all (from 1:80 to 1:320 in bacterial agglutination tests and from 1:8 to 1:32 in complement fixation tests) but one patient (patient 1), in whom fecal culture revealed Y. enterocolitica. In addition, Y. enterocolitica was isolated and identified in the feces of three other patients. When colonoscopies were performed, five of the patients (patients 1 through 5) complained of right lower abdominal pain and ileocecal tenderness was confirmed in all patients. In all patients, the entire colon and the terminal ileum were able to be observed. No abnormalities were found in the left side of the colon. The endoscopic findings in the right side of the colon and in the terminal ileum are summarized in Table 2. In all patients, the terminal ileum was affected. The specific findings were edema, reddened mucosa, round or oval elevations, small or large irregular-shaped, shallow ulcers, or some combination of these. In patient 1, who had a relatively short interval from the onset of symptoms until colonoscopy, edema and large elevations without ulceration were detected (Fig. lA). In patient 8, who had a long interval from the onset of symptoms until colonoscopy, small elevations and edematous reddened mucosa were observed. In patient 2, edema and multiple ulcers were noted but no elevations could be found (Fig. IB). In patient 5, only small elevations were seen. In the remaining four patients, edema, ulcers, and elevations were all found (Fig. lC). In five of the eight patients, the ileocecal valve was detected as abnormal. The findings included swelling, small ulcers (Fig. ID), and erosions. VOLUME 36, NO.6, 1990
In all patients whose ileocecal valve was affected, the cecum was also involved. There were small ulcers surrounded by reddish and slightly elevated mucosa (aphthoid ulcers) in these patients. In addition, there were small, round elevations in the cecum of one patient whose ileocecal valve was not affected. The ascending colon was less frequently involved. Only two patients were affected, one with aphthoid ulcers and the other with round elevations. In all patients, biopsies were obtained from the elevations, from the margin of ulcers, or from aphthoid ulcers. Histological examination of the specimens revealed lymphocytic cell infiltration with lymphoid follicles in the mucosa and submucosa of the ileum and the colon. However, Y. enterocolitica was not seen on histological examination of any biopsy specimen. In each patient, complete healing of the lesions was on barium follow-through or barium enema examination 1 to 2 months after colonoscopy.
DISCUSSION
Since the first report by Winblad et al. in 1966,3 acute enterocolitis in adults and adolescents caused by Y. enterocolitica has been increasingly reported all over the world, especially in Scandinavia,6 Western Europe/ 6,l? Canada,9,l8 and Japan. l The high frequency of diagnosis is probably owing to the establishment of a method to isolate and identify the organism. l4 Although various gastrointestinal features in relation to serotypes of Y. enterocolitica, which may be partly due to geographic characteristics, have been recently suggested,9 ileitis with mesenteric adenitis is still considered to be a major manifestation of the infection. In our study, microbiological confirmation of Y. enterocolitica was made in four patients whereas in the remaining four patients, the diagnosis was based on serologic methods. The failure to culture Yersinia species is probably due to the fact that the coldenrichment technique, which has been described as being necessary for Y. enterocolitica,14 was insufficient in these patients. Although the serologic method is reported to have numerous limitations,19 we considered that elevated antibody titers had diagnostic value in those patients who were suffering from acute enterocolitis. Few studies have been reported concerning the colonoscopic features of Y. enterocolitis. Vantrappen et al. 8 performed sigmoidoscopy and/or colonoscopy in 13 of 37 cases of Y. enterocolitica infections and observed aphthoid ulcers in the left side of the colon in two patients and swollen erythematous mucosa in six patients. Rutgeerts et al. 12 later reported on the colonoscopic findings of 21 cases of Yersinia colitis and demonstrated aphthoid ulcers mainly in the right side of the colon. They reported that rectosigmoidoscopy 585
may not reveal any colonic involvement in Yersinia enterocolitis. In this study, all patients were affected in the terminal ileum, with frequent involvement of the ileocecal valve and the cecum. However, the left side of the colon was never affected. This distribution of lesions in Y. enterocolitis suggests the necessity of total colonoscopy for the diagnosis of this disease. The most common finding in the colon was aphthoid ulcers, as described in previous reports. 8 ,12 Recently, however, colitis on the left side of the colon, which was masquerading as pseudomembranous colitis, caused by Y. enterocolitica serotype 0:8, has been reported in the United States. 20 In a Canadian study, Simmonds et al. 9 found inflammatory changes or pseudomembranous colitis in 16 of 62 patients with culture-positive Y. enterocolitica, where serotype 0:3 was not prominent. The uniform colonoscopic findings in our patients with serotype 0:3, which is obviously different from the findings in the above-mentioned reports, would support the suggestion that serotypes found in North America could react in a different way from serotype 0:3. 9 Rutgeerts et al. 12 demonstrated the endoscopic view of the terminal ileum in Y. enterocolitis, and they described large ulcerations and granular mucosa as the prominent features. To our knowledge, further reports concerning endoscopy in Yersinia ileitis have not been published. In Japan, Arai et al. 13 found multiple coarse granular elevations in the terminal ileum in a Yersinia ileitis patient. Our study revealed the endoscopic findings in Yersinia ileitis to consist of round or oval elevations, shallow and irregular ulcers of various sizes, or some combination of these, scattered throughout the edematous mucosa. Considering the affinity of Y. enterocolitica to the lymphatic systems 1 and the histological features showing lymphoid hyperplasia in our patients, the elevations are probably caused by reactive hyperplasia of Peyer's patches, which are anatomically prominent in the terminal ileum. As the elevations of the patients who also had ulcers were smaller than those of the patient without ulcers, in whom the most prompt colonoscopy from the onset of symptoms was performed, it was speculated that ulcer formation was preceded by initial lymphoid hyperplasia induced by Yersinia infection. In addition, the formation of ulceration was considered to depend either on the severity of the infection or on the therapy applied. Contrary to reports dealing with endoscopic findings, radiological characteristics have been described in several reports. 8 , 10,21,22 Vantrappen et al. 8 analyzed the radiological findings of 24 Yersinia terminal ileitis patients and concluded that coarse folds, nodules, and granules were occasional signs. In their report, oval or longitudinal ulcers were also pointed out but these 586
were found less frequently. Ekberg et al. lO classified the radiographic changes of Yersinia terminal ileitis into three stages, the last one of which was the stage of resolution observed during the weeks 5 to 8, showing diffusely scattered nodules. However, there was no mention of ulcerations as notable signs. The small, shallow ulcers detected in our cases by endoscopy would be difficult to demonstrate in the affected narrow lumen on contrast radiographs. In this report, we could not show any distinct correlation between the duration of illness and the endoscopic findings in Y. enterocolitis. However, Y. enterocolitica may cause not only mutiple elevations as previously detected on radiographs but also multiple ulcers in the terminal ileum and the colon even 4 to 5 weeks after the onset of symptoms. This correlates well with a patient described by Moeller and Burger23 who developed ileal perforation 5 weeks after the initial symptoms occurred. As this study was based on one-point colonoscopy in each patient, further serial endoscopic examinations should be attempted in order to more precisely describe the natural course of this disease.
REFERENCES 1. Zen-Yoji H, Maruyama T. The first successful isolations and identification of Yersinia enterQColitica from human cases in Japan. Jpn J Microbiol 1972;16:493-500. 2. Kohl S. Yersinia enterQColitica infections in children. Pediatr Clin North Am 1979;26:433-43. 3. Winblad S, Nilehn B, Sternby NH. Yersinia enterocolitica (Pasteurella X) in human enteric infections. Br Med J 1966;2:13636. 4. Olinde AJ, Lucas JF, Miller RC. Acute yersinosis and its surgical significance. South Med J 1984;77:1539-44. 5. Leino R, Kalliomaki JL. Yersinosis as an internal disease. Ann InternMed 1974;81:458-61. 6. Laitinen 0, Tuuhea J, Ahvonen P. Polyarthritis associated with Yersinia enterocolitica infection. Ann Rheum Dis 1972;31:34-9. 7. Chessum B, Frengley JD, Fleck DG, Mair NS. Case of septicemia due to Yersinia enterocolitica. Br Med J 1971;3:466. 8. Vantrappen G, Agg HO, Ponette E, Geboes K, Bertrand PH. Yersinia enteritis and enterocolitis: gastrointestinal aspects. Gastroenterology 1977;72:220-7. 9. Simmonds SD, Noble MA, Freeman HJ. Gastrointestinal features of culture-positive Yersinia enterQColitica infection. Gastroenterology 1987;92:112-7. 10. Ekberg 0, Sjostrom B, Brahme F. Radiological findings in Yersinia ileitis. Radiology 1977; 123:15-9. 11. Puylaert JBCM. Mesenteric adenitis and acute terminal ileitis: US evaluation using graded compression. Radiology 1986;161691-5. 12. Rutgeerts P, Geboes K, Ponette E, Coremans G, Vantrappen G. Acute infective colitis caused by endemic pathogens in Western Europe. Endoscopy 1982;14:212-9. 13. Arai Y, Matsumoto J. Odashima H. Analysis of endoscopic findings in acute terminal ileitis. Gastroenterol Endosc 1982;24:1439-44. 14. Pai CH, Sorger S, Lafleur L, Marks MI. Efficacy of cold enrichment techniques for recovery of Yersinia enterocolitica from human stools. J Clin Microbiol 1979;9:712-5. 15. Hurvell B, Ahvonen p. ThaI E. Serological cross-reactions between different Brucella species and Yersinia enterocolitica. Agglutination and complement fixation. Acta Vet Scand 1971;12:86-90.
GASTROINTESTINAL ENDOSCOPY
16. Mollaret HH. L'infection humaine a "Yersinia enterocolitica" en 1970, a la lumiere de 642 cas recents (aspects cliniques et perspectives epidemiolobiques). Pathol BioI (Paris) 1971;19: 189-205. 17. Vandepitte J, Wauters G, Isebaert A. Epidemiology of Yersinia enterocolitica infections in Belgium. Contrib Microbiol ImmunoI1973;2:111-9. 18. Toma S, Lafleur L. Survey on the incidence of Yersinia enterocolitica infection in Canada. Appl MicrobioI1974;28:469-73. 19. Bottone EJ, Sheehan DJ. Yersinia enterocolitica. Guidelines for serologic diagnosis of human infections. Rev Infect Dis
VOLUME 36, NO.6, 1990
1983;5:898-906. 20. Brown R, Tedesco FJ, Assad RT, Rao R. Yersinia colitis masquerading as pseudomembranous colitis. Dig Dis Sci 1986;31: 548-51. 21. Shrago G. Yersinia enterocolitica ileocolitis findings observed on barium examination. Br J Radiol 1976;49:181-3. 22. van Wiechen PJ. Radiological changes in the distal part of the ileum in association with Yersinia enterocolitica infections. Radiol Clin Bioi 1974;43:242-53. 23. Moeller DD, Burger WE. Perforation of the ileum in Yersinia enterocolitica infection. Am J GastroenteroI1985;80:19-20.
587
Endoscopic findings in Yersinia enterocolitica enterocolitis Takayuki Matsumoto, MD, Mitsuo Iida, Toshiyuki Matsui, MD, Kiyoto Sakamoto, Tadahiko Fuchigami, MD, Yukiaki Haraguchi, Masatoshi Fujishima,
MD MD MD MD
Fukuoka and Matsuyama, Japan
The endoscopic findings in the colon and terminal ileum in eight cases of Yersinia enterocolitica enterocolitis infection were studied. The diagnosis was based on the isolation of Y. enterocolitica in the feces and/or elevated serum antibody titers to the organism. Total colonoscopy was performed between 7 and 38 days (mean, 24 days) after the onset of symptoms. In all patients, the terminal ileum was affected, followed by frequent involvement of the ileocecal valve and the cecum, and less frequently, the ascending colon. In the terminal ileum, round or oval elevations with or without ulcers were detected. Small ulcers were detected on the ileocecal valve and in the cecum. These findings were observed even 4 to 5 weeks after the onset of symptoms, suggesting a relatively long course for this disease. (Gastrointest Endosc 1990;36:583-587)
Yersinia enterocolitica is a gram-negative rod resembling non-lactose-fermenting Escherichia coli. During the 1960s and the 1970s, it became recognized as a human pathogen in many countries including Japan. 1 Clinically, it causes acute enteritis with fever in infants 2 whereas, in adolescents and adults, acute terminal ileitis with mesenteric adenitis frequently occurs, which is often misdiagnosed as acute appendicitis. 3.4 It is also known to cause erythema nodosum,5 polyarthritis,6 and septicemia.? Although many studies concerning gastrointestinal
manifestations of Y. enterocolitica have shown its clinical,8.9 radiological,IO and ultrasonic l l features precisely, little is known about the endoscopic characteristics of this infection.8.12.13 With the development of total colonoscopy, we have been able to examine eight cases of Y. enterocolitica enterocolitis endoscopically during a 9-year period.
Received February 10, 1990. For revision April 1, 1990. Accepted July 12, 1990. From the Second Department of Internal Medicine, Kyushu University, the Department of Internal Medicine, Kyushu Central Hospital and the Division of Gastroenterology, Sawara Hospital, Fukuoka, Japan, and the Matsuyama Red Cross Hospital, Matsuyama, Japan. Reprint requests: T. Matsumoto, MD, Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Maidaishi3-1-1, Higashi-ku, Fukuoka 812, Japan. VOLUME 36, NO.6, 1990
PATIENTS AND METHODS
During the past 9 years (from 1980 to 1989), we performed total colonoscopy in eight patients with enterocolitis caused by Y. enterocolitica. The diagnosis was based on the isolation of Y. enterocolitica in the feces and/or elevated serum antibody titers to this organism. In each patient, both fecal culture and serological examinations against Y. enterocolitica were performed. Fecal culture was performed by both the method described by ZenYoji and Maruyama! and a cold-enrichment technique" of 7 to 14 days. Antibody titers were measured by bacterial agglutination tests3 in patients 2, 4, 6, 7, and 8 and comple-
ment fixation tests!5 in patients 1, 3, and 5. Both of these tests were undertaken with a 0:3 antigen preparation, since this serotype of Y. enterocolitica is the most common form in Japan.! Colonoscopy, with models CF-lOL, CF-20I, or CFV-10I (Olympus Corporation, Tokyo, Japan) for all but one patient (patient 5), for whom a PCF-lO was used, was performed between 7 and 38 days (mean, 24 days) from the onset of symptoms. In each patient, total colonoscopy was indicated because of the possibility that the patient had Crohn's ileocolitis or some other inflammatory process. Such possibilities were suggested by the results of a preceding barium followthrough or barium enema examination. RESULTS
The clinical features of the patients are summarized in Table 1. There were three male and five female 583
Table 1. Summary of patients Age (yr)
Sex
1
16
F
2
41
F
3
28
M
4
35
M
5
11
M
6
65
F
7
42
F
8
32
F
Patient
Symptoms Right lower abdominal pain Epigastric and lower abdominal pain Right lower abdominal pain; nausea Periumbilical pain; diarrhea; nausea Right lower abdominal pain; nausea Fever; low back and right knee pain Upper abdominal pain; anorexia Right lower abdominal pain; diarrhea
ESR" (mm/hr)
CRP
34
Time interval
WBC (mm")
Y. enterocolitica antibody
Y. enterocolitica culture
(3+)
9,200
(±)
(+)
7
73
(-)
4,800
(+)
(-)
13
15
(1+)
9,300
(+)
(+)
21
10
(1+)
10,300
(+)
(-)
24
6
(-)
9,500
(+)
(-)
26
72
(-)
11,200
(+)
(-)
27
42
(-)
11,900
(+)
(+)
32
30
(±)
9,600
(+)
(+)
38
(daYS)b
" ESR, erythrocyte sedimentation rate; CRP, C-reactive protein. b Time interval from the onset of symptoms until colonoscopy.
Table 2. Summary of colonoscopic findings Ascending colon
Patient
Terminal ileum
Ileocecal valve
Cecum
1
Large round or oval elevations with erosions; edema Ulcers (large and small); edema, reddened mucosa Small ulcers; small, round elevations; edema; reddened mucosa Ulcers (large and small); small, round elevations; edema; reddened mucosa Small, round elevations Ulcers (large and small); small, round elevations; edema; reddened mucosa Small ulcers; edema; small, round elevations Small, round elevations; edema; reddened mucosa
Small ulcer; swelling
Aphthoid ulcers
NP"
Small ulcer; swelling
Aphthoid ulcers
Aphthoid ulcers
Small ulcers; erosions; swelling
Aphthoid ulcers
NP
Erosions; swelling
Aphthoid ulcers
NP
NP Swelling
NP Aphthoid ulcers
NP NP
NP
NP
NP
NP
Small, round elevations
Small, round elevations
2
3
4
5 6
7
8
" NP, no particular findings.
patients. The age of the patients ranged from 11 to 65 years, with a mean of 34 years. Gastrointestinal symptoms and ileocecal tenderness were noted in all patients. In one patient (patient 6), arthropathy due to 584
Yersinia infection was suspected. There was an accelerated erythrocyte sedimentation rate in five patients, positive C-reactive protein in three patients, and leucocytosis in seven patients. Increased serum antibody GASTROINTESTINAL ENDOSCOPY
Figure 1. A, Endoscopic view of the terminal ileum in patient
1; multiple round or oval elevations with erosions can be seen. B, Endoscopic view of the terminal ileum in patient 2; large, shallow, irregular-shaped ulcers can be seen. C, Endoscopic view of the terminal ileum in patient 4; multiple small ulcers and a few round elevations can be seen. D, Endoscopic view of the ileocecal valve in patient 1; small ulcers can be seen.
titers to Y. enterocolitica serotype 0:3 were detected in all (from 1:80 to 1:320 in bacterial agglutination tests and from 1:8 to 1:32 in complement fixation tests) but one patient (patient 1), in whom fecal culture revealed Y. enterocolitica. In addition, Y. enterocolitica was isolated and identified in the feces of three other patients. When colonoscopies were performed, five of the patients (patients 1 through 5) complained of right lower abdominal pain and ileocecal tenderness was confirmed in all patients. In all patients, the entire colon and the terminal ileum were able to be observed. No abnormalities were found in the left side of the colon. The endoscopic findings in the right side of the colon and in the terminal ileum are summarized in Table 2. In all patients, the terminal ileum was affected. The specific findings were edema, reddened mucosa, round or oval elevations, small or large irregular-shaped, shallow ulcers, or some combination of these. In patient 1, who had a relatively short interval from the onset of symptoms until colonoscopy, edema and large elevations without ulceration were detected (Fig. lA). In patient 8, who had a long interval from the onset of symptoms until colonoscopy, small elevations and edematous reddened mucosa were observed. In patient 2, edema and multiple ulcers were noted but no elevations could be found (Fig. IB). In patient 5, only small elevations were seen. In the remaining four patients, edema, ulcers, and elevations were all found (Fig. lC). In five of the eight patients, the ileocecal valve was detected as abnormal. The findings included swelling, small ulcers (Fig. ID), and erosions. VOLUME 36, NO.6, 1990
In all patients whose ileocecal valve was affected, the cecum was also involved. There were small ulcers surrounded by reddish and slightly elevated mucosa (aphthoid ulcers) in these patients. In addition, there were small, round elevations in the cecum of one patient whose ileocecal valve was not affected. The ascending colon was less frequently involved. Only two patients were affected, one with aphthoid ulcers and the other with round elevations. In all patients, biopsies were obtained from the elevations, from the margin of ulcers, or from aphthoid ulcers. Histological examination of the specimens revealed lymphocytic cell infiltration with lymphoid follicles in the mucosa and submucosa of the ileum and the colon. However, Y. enterocolitica was not seen on histological examination of any biopsy specimen. In each patient, complete healing of the lesions was on barium follow-through or barium enema examination 1 to 2 months after colonoscopy.
DISCUSSION
Since the first report by Winblad et al. in 1966,3 acute enterocolitis in adults and adolescents caused by Y. enterocolitica has been increasingly reported all over the world, especially in Scandinavia,6 Western Europe/ 6,l? Canada,9,l8 and Japan. l The high frequency of diagnosis is probably owing to the establishment of a method to isolate and identify the organism. l4 Although various gastrointestinal features in relation to serotypes of Y. enterocolitica, which may be partly due to geographic characteristics, have been recently suggested,9 ileitis with mesenteric adenitis is still considered to be a major manifestation of the infection. In our study, microbiological confirmation of Y. enterocolitica was made in four patients whereas in the remaining four patients, the diagnosis was based on serologic methods. The failure to culture Yersinia species is probably due to the fact that the coldenrichment technique, which has been described as being necessary for Y. enterocolitica,14 was insufficient in these patients. Although the serologic method is reported to have numerous limitations,19 we considered that elevated antibody titers had diagnostic value in those patients who were suffering from acute enterocolitis. Few studies have been reported concerning the colonoscopic features of Y. enterocolitis. Vantrappen et al. 8 performed sigmoidoscopy and/or colonoscopy in 13 of 37 cases of Y. enterocolitica infections and observed aphthoid ulcers in the left side of the colon in two patients and swollen erythematous mucosa in six patients. Rutgeerts et al. 12 later reported on the colonoscopic findings of 21 cases of Yersinia colitis and demonstrated aphthoid ulcers mainly in the right side of the colon. They reported that rectosigmoidoscopy 585
may not reveal any colonic involvement in Yersinia enterocolitis. In this study, all patients were affected in the terminal ileum, with frequent involvement of the ileocecal valve and the cecum. However, the left side of the colon was never affected. This distribution of lesions in Y. enterocolitis suggests the necessity of total colonoscopy for the diagnosis of this disease. The most common finding in the colon was aphthoid ulcers, as described in previous reports. 8 ,12 Recently, however, colitis on the left side of the colon, which was masquerading as pseudomembranous colitis, caused by Y. enterocolitica serotype 0:8, has been reported in the United States. 20 In a Canadian study, Simmonds et al. 9 found inflammatory changes or pseudomembranous colitis in 16 of 62 patients with culture-positive Y. enterocolitica, where serotype 0:3 was not prominent. The uniform colonoscopic findings in our patients with serotype 0:3, which is obviously different from the findings in the above-mentioned reports, would support the suggestion that serotypes found in North America could react in a different way from serotype 0:3. 9 Rutgeerts et al. 12 demonstrated the endoscopic view of the terminal ileum in Y. enterocolitis, and they described large ulcerations and granular mucosa as the prominent features. To our knowledge, further reports concerning endoscopy in Yersinia ileitis have not been published. In Japan, Arai et al. 13 found multiple coarse granular elevations in the terminal ileum in a Yersinia ileitis patient. Our study revealed the endoscopic findings in Yersinia ileitis to consist of round or oval elevations, shallow and irregular ulcers of various sizes, or some combination of these, scattered throughout the edematous mucosa. Considering the affinity of Y. enterocolitica to the lymphatic systems 1 and the histological features showing lymphoid hyperplasia in our patients, the elevations are probably caused by reactive hyperplasia of Peyer's patches, which are anatomically prominent in the terminal ileum. As the elevations of the patients who also had ulcers were smaller than those of the patient without ulcers, in whom the most prompt colonoscopy from the onset of symptoms was performed, it was speculated that ulcer formation was preceded by initial lymphoid hyperplasia induced by Yersinia infection. In addition, the formation of ulceration was considered to depend either on the severity of the infection or on the therapy applied. Contrary to reports dealing with endoscopic findings, radiological characteristics have been described in several reports. 8 , 10,21,22 Vantrappen et al. 8 analyzed the radiological findings of 24 Yersinia terminal ileitis patients and concluded that coarse folds, nodules, and granules were occasional signs. In their report, oval or longitudinal ulcers were also pointed out but these 586
were found less frequently. Ekberg et al. lO classified the radiographic changes of Yersinia terminal ileitis into three stages, the last one of which was the stage of resolution observed during the weeks 5 to 8, showing diffusely scattered nodules. However, there was no mention of ulcerations as notable signs. The small, shallow ulcers detected in our cases by endoscopy would be difficult to demonstrate in the affected narrow lumen on contrast radiographs. In this report, we could not show any distinct correlation between the duration of illness and the endoscopic findings in Y. enterocolitis. However, Y. enterocolitica may cause not only mutiple elevations as previously detected on radiographs but also multiple ulcers in the terminal ileum and the colon even 4 to 5 weeks after the onset of symptoms. This correlates well with a patient described by Moeller and Burger23 who developed ileal perforation 5 weeks after the initial symptoms occurred. As this study was based on one-point colonoscopy in each patient, further serial endoscopic examinations should be attempted in order to more precisely describe the natural course of this disease.
REFERENCES 1. Zen-Yoji H, Maruyama T. The first successful isolations and identification of Yersinia enterQColitica from human cases in Japan. Jpn J Microbiol 1972;16:493-500. 2. Kohl S. Yersinia enterQColitica infections in children. Pediatr Clin North Am 1979;26:433-43. 3. Winblad S, Nilehn B, Sternby NH. Yersinia enterocolitica (Pasteurella X) in human enteric infections. Br Med J 1966;2:13636. 4. Olinde AJ, Lucas JF, Miller RC. Acute yersinosis and its surgical significance. South Med J 1984;77:1539-44. 5. Leino R, Kalliomaki JL. Yersinosis as an internal disease. Ann InternMed 1974;81:458-61. 6. Laitinen 0, Tuuhea J, Ahvonen P. Polyarthritis associated with Yersinia enterocolitica infection. Ann Rheum Dis 1972;31:34-9. 7. Chessum B, Frengley JD, Fleck DG, Mair NS. Case of septicemia due to Yersinia enterocolitica. Br Med J 1971;3:466. 8. Vantrappen G, Agg HO, Ponette E, Geboes K, Bertrand PH. Yersinia enteritis and enterocolitis: gastrointestinal aspects. Gastroenterology 1977;72:220-7. 9. Simmonds SD, Noble MA, Freeman HJ. Gastrointestinal features of culture-positive Yersinia enterQColitica infection. Gastroenterology 1987;92:112-7. 10. Ekberg 0, Sjostrom B, Brahme F. Radiological findings in Yersinia ileitis. Radiology 1977; 123:15-9. 11. Puylaert JBCM. Mesenteric adenitis and acute terminal ileitis: US evaluation using graded compression. Radiology 1986;161691-5. 12. Rutgeerts P, Geboes K, Ponette E, Coremans G, Vantrappen G. Acute infective colitis caused by endemic pathogens in Western Europe. Endoscopy 1982;14:212-9. 13. Arai Y, Matsumoto J. Odashima H. Analysis of endoscopic findings in acute terminal ileitis. Gastroenterol Endosc 1982;24:1439-44. 14. Pai CH, Sorger S, Lafleur L, Marks MI. Efficacy of cold enrichment techniques for recovery of Yersinia enterocolitica from human stools. J Clin Microbiol 1979;9:712-5. 15. Hurvell B, Ahvonen p. ThaI E. Serological cross-reactions between different Brucella species and Yersinia enterocolitica. Agglutination and complement fixation. Acta Vet Scand 1971;12:86-90.
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16. Mollaret HH. L'infection humaine a "Yersinia enterocolitica" en 1970, a la lumiere de 642 cas recents (aspects cliniques et perspectives epidemiolobiques). Pathol BioI (Paris) 1971;19: 189-205. 17. Vandepitte J, Wauters G, Isebaert A. Epidemiology of Yersinia enterocolitica infections in Belgium. Contrib Microbiol ImmunoI1973;2:111-9. 18. Toma S, Lafleur L. Survey on the incidence of Yersinia enterocolitica infection in Canada. Appl MicrobioI1974;28:469-73. 19. Bottone EJ, Sheehan DJ. Yersinia enterocolitica. Guidelines for serologic diagnosis of human infections. Rev Infect Dis
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1983;5:898-906. 20. Brown R, Tedesco FJ, Assad RT, Rao R. Yersinia colitis masquerading as pseudomembranous colitis. Dig Dis Sci 1986;31: 548-51. 21. Shrago G. Yersinia enterocolitica ileocolitis findings observed on barium examination. Br J Radiol 1976;49:181-3. 22. van Wiechen PJ. Radiological changes in the distal part of the ileum in association with Yersinia enterocolitica infections. Radiol Clin Bioi 1974;43:242-53. 23. Moeller DD, Burger WE. Perforation of the ileum in Yersinia enterocolitica infection. Am J GastroenteroI1985;80:19-20.
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