Clin J Gastroenterol (2010) 3:30–35 DOI 10.1007/s12328-009-0132-6
CASE REPORT
Perforation of rectal diverticulum with amyloidosis secondary to rheumatoid arthritis: case report and review of the literature Daisuke Takeuchi • Naohiko Koide • Masato Kitazawa Kazuhiro Fukushima • Masayuki Matsuda • Mana Fukushima • Shinichi Miyagawa
•
Received: 6 September 2009 / Accepted: 22 November 2009 / Published online: 23 December 2009 Ó Springer 2009
Abstract We report a case of perforation of a rectal diverticulum with amyloidosis secondary to rheumatoid arthritis (RA), and review the clinicopathologic features in 21 Japanese amyloidosis patients with colorectal perforation. A 62-year-old woman with amyloidosis secondary to RA suddenly complained of abdominal pain. Computed tomography (CT) showed ascites and free air in the abdominal cavity, and many diverticula with calculi in the sigmoid colon. Emergent surgery was performed for acute peritonitis. We observed the perforation, 5 mm in diameter, of a diverticulum in the upper rectum, and many diverticula located in the upper rectum and sigmoid colon. Anterior resection of the rectum combined with sigmoidectomy was performed. The resected specimen showed many diverticula including fecaliths, approximately 7 mm in size. Histopathologically, many inflammatory cells had infiltrated around the perforation. On Congo red staining, amyloid deposits were observed in or around the small blood vessels of the lamina propria mucosa and submucosa of the rectum. Although colorectal perforation with amyloidosis secondary to RA is rare, this complication was associated with poor prognosis. Furthermore, in
D. Takeuchi N. Koide (&) M. Kitazawa S. Miyagawa Department of Surgery, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto 390-8621, Japan e-mail: [email protected] K. Fukushima M. Matsuda Department of Internal Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, Matsumoto, Japan M. Fukushima Department of Clinical Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, Japan
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patients with amyloidosis, we should be careful regarding the management of colorectal diverticula. Keywords Perforation Rectum Amyloidosis Rheumatoid arthritis Diverticula
Introduction Rheumatoid arthritis (RA) can occasionally complicate the development of reactive or secondary amyloidosis, which shows the deposition of amyloid A in several organs, and this complication can lead to a high risk of organ failure and mortality [1, 2]. Amyloid A fibrils originate from a fragment of serum amyloid A protein [3]. Chronic inflammatory conditions, of which the foremost is RA, develop and stimulate amyloid A amyloidosis in several organs [2]. Amyloidosis frequently involves the gastrointestinal (GI) tract [4, 5]. Reactive amyloidosis secondary to RA is also frequently observed in the GI tract, and the histological diagnosis is based on endoscopic biopsy tissues of the GI tract [6]. On the other hand, acute abdominal complications, including hemorrhage, pseudo-obstruction, and GI tract perforation, are uncommon in patients with amyloidosis; however, the clinical outcome in amyloidosis patients with perforation of the GI tract, including both the upper and lower tracts, has been poor [7]. Perforation of the colon and rectum has exceptionally been reported in patients with amyloidosis, and rectal perforation was reported in a few cases with amyloidosis [8, 9]. However, in amyloidosis patients secondary to RA with colorectal perforation, the clinicopathologic features and outcome are not yet well known. We report herein a case of perforation of a rectal diverticulum with amyloidosis secondary to RA, and
Clin J Gastroenterol (2010) 3:30–35
review and discuss the clinicopathologic features and outcomes in 21 Japanese amyloidosis patients with colorectal perforation reported over the last two decades.
Case report A 62-year-old woman, who was admitted for the initiation of hemodialysis, suddenly complained of severe abdominal pain. From 16 years ago, the patient has been treated for RA with prednisolone. Nine years ago, a gastric polyp was detected by esophagogastroscopy, and biopsy specimens taken from the polyp histologically showed amyloid A deposition. Furthermore, amyloid deposits were histologically noted in biopsy specimens taken from the right kidney because of renal dysfunction, which has not been associated with hemodialysis (HD), and secondary amyloidosis associated with RA was diagnosed. Recently, the patient complained of constipation. Physical examination showed a 37.9°C temperature, tachycardia, and severe tenderness with muscle defense of the lower abdomen. Blood examination showed leukocytosis (15,270/ll) with neutrophilia (97.9%), and blood chemistry revealed elevated serum levels of C-reactive protein (14.2 mg/dl), blood urea nitrogen (114.0 mg/dl), and creatinine (4.38 mg/dl). Blood gas analysis identified severe metabolic acidosis (base excess; -14.3 mmol/l), hypoxia (66.8 mmHg), and hypocarboxia (23.4 mmHg). Computed tomography (CT) showed the presence of ascites and free air in the abdominal cavity (Fig. 1a), and many diverticula with intestinal calculi in the sigmoid colon (Fig. 1b). Emergent surgery was performed for acute peritonitis suspected to have been caused by colonic perforation. On laparotomy, we observed dirty ascites (3,100 ml), and the perforation of a diverticulum in the upper rectum 3 cm above the peritoneal turning of Douglas pouch (Fig. 2). Many diverticula were located in the upper rectum and sigmoid colon. However, neither acute ischemic nor congestive findings of the rectum or sigmoid colon were observed. Each diverticulum included a hard stone-like substance, a so-called intestinal calculus or fecalith. We
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conducted anterior resection of the rectum combined with sigmoidectomy, and performed a colostomy (Hartmann’s procedure). The diverticula were included in the resected colorectum. The patient was immediately admitted to the intensive care unit after surgery for emergent hemodialysis and endotoxin-absorption therapy using a column of polymyxin B-immobilized fibers, but the postoperative course was uneventful. Macroscopically, the perforation was 5 mm in diameter on the tenial side of the upper rectum (Fig. 3a). The resected specimen showed many diverticula (Fig. 3b), and a fecalith, approximately 7 mm in size, was included in each diverticulum. The colonic wall of these diverticula seemed to be very thin, and we could observe these fecaliths through the thin colonic wall (Fig. 3c). Neither acute ischemic nor congestive finding of the resected specimen were observed. Histopathologically, many inflammatory cells had infiltrated around the perforation (Fig. 4a, b). Congo-red-stained amyloid (pink-red deposit) was observed in the stroma of the lamina propria mucosa and submucosa of the rectum, especially in or around the small blood vessels (Fig. 4c, d). Furthermore, narrow blood vessel lumens caused by amyloid deposition were occasionally observed.
Discussion Amyloidosis, including primary and secondary diseases, frequently progresses to several organ disorders due to abnormal extracellular amyloid deposition. In patients undergoing HD, the frequency of secondary amyloidosis has increased [10]. In secondary amyloidosis patients associated with RA, the initiation of HD for end-stage renal disease leads to poor survival [11]. In the present patient, RA has been treated for 16 years, and amyloid deposits have been evidenced using gastric and renal biopsy specimens. HD has not yet been performed, although it is scheduled in the near future. Therefore, the present patient was considered to show secondary amyloidosis associated with RA.
Fig. 1 Abdominal CT findings. a CT shows peritoneal ascites (arrowheads) and free air (arrow) in the abdominal cavity. b CT shows many diverticula of the sigmoid colon, and the diverticula include an intestinal calculus
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Fig. 2 Operative findings. The arrow shows a perforation of the upper rectum, with a diameter of 5 mm. However, the rectum and sigmoid colon show no acute ischemia or congestion
Fig. 3 Macroscopic findings. a A perforation (arrow) was detected in the upper rectum, and the diverticula were completely resected in the upper rectum and sigmoid colon. b The mucosal side. Arrowheads show many diverticula in the upper rectum and sigmoid colon. c The serosal side. Arrowheads show many diverticula, and the fecaliths are covered with the thin colon wall
In GI amyloidosis, colorectal perforation has been exceptional, and this complication has been explained by several factors. Amyloid deposition in the GI tract was frequently observed in or around the wall of blood vessels in the lamina propria mucosa and submucosa [4], and amyloid A deposits were observed in the small blood vessels of the submucosa of the GI tract in patients with secondary amyloidosis [12], such as in the present case. As a reason for intestinal perforation, it is well known that amyloid deposition can lead to occlusion of blood vessels or their luminal narrowing, and can result in local ischemia of the GI wall. Consequently, these factors cause GI tract perforation. In the present case, amyloid deposits were observed in the small blood vessels of the lamina propria mucosa and submucosa of the rectum and sigmoid colon. Narrowing of the blood vessel lumens by amyloid deposition, which can lead to weakening of the intestinal wall,
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was also observed. Several types of mechanism of intestinal perforation associated with amyloidosis have been considered, but are not sufficiently understood. As another type of intestinal perforation in patients with amyloidosis, megacolon caused by amyloid deposits in the proper muscle layer has been considered [13]. In the present case, this finding was not observed. Furthermore, Orita et al. [14] reported a case of HD-related amyloidosis with colonic perforation due to ileus. It was noted that this perforation occurred in the rectal diverticulum, and many diverticula containing fecaliths were observed. Amyloid deposition occurs in paralysis of the intestine, and clinically results in constipation. Gastrointestinal neuropathy associated with amyloid deposition in the autonomic nerves has been observed in amyloidosis patients with intestinal pseudo-obstruction [12]. Furthermore, Stollman and Raskin [15] described increased intracolonic pressures in patients with diverticulosis. It was straightforward to consider that the presence of many diverticula and fecaliths occurs due to constipation. The diverticulitis occurred due to fecalith presence, and the perforation of the rectal diverticulum may have resulted in the present case. Therefore, in patients with amyloidosis, we should be careful regarding the management of constipation and colorectal diverticula. In addition, we noted steroid-associated diverticulitis and perforation of the GI tract. The present RA patient has undergone long-term prednisolone treatment. Arsura [16] described a relationship between colonic diverticula perforation and corticosteroid use, and Tyau et al. [17] reported that diverticular perforation was frequently observed in immunocompromised patients, including those using steroids. Furthermore, corticosteroid treatment showed a close association with sigmoid diverticular abscess perforation under rheumatic conditions [18]. Therefore, the perforation in this case may be explained by several factors, including secondary amyloid deposition of the colorectum, and diverticulitis caused by fecaliths associated with long-term steroid treatment for RA. Twenty Japanese amyloidosis patients with colorectal perforation, identified by searching PubMed and Japana Centra Revuo Medicina, were reported in the last decade (between 1989 and 2008), excluding supplements. A review of the clinicopathologic features of the 21 patients [9, 13, 14, 19–34], including the present case, is summarized in Table 1. The gender ratio (man/woman) was 1.63, and the mean age of these cases was 63 years. Regarding the site of perforation, the most common site was the sigmoid colon, and 85.7% of perforations were observed in the left colon. Rectal perforation was observed in 3 patients, including the present case (14.3%). Primary amyloidosis was observed in 6, while secondary amyloidosis was observed in 15 (71.4%). Amyloidosis secondary
Clin J Gastroenterol (2010) 3:30–35
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Fig. 4 Histopathologic findings. a Hematoxylin and eosin (HE) staining of the perforated diverticulum (920). The upper area of the photograph shows the luminal side of the rectum. The central part shows the perforated site. b HE staining of the lamina propria mucosa and submucosa near the perforated diverticulum (9200). Inflammatory cells infiltrating the stroma of the diverticulum are observed in or around the small blood vessels. c Congo red staining of the perforated diverticulum (920). The photograph was taken using a serial section to that of a. d Congo red staining of the lamina propria mucosa and submucosa near the perforated diverticulum (9200). Congored-stained amyloid (pink–red deposit) is observed in or around the small blood vessels (color figure online)
Table 1 Amyloidosis patients with colorectal perforation reported over the last two decades Case
Author
Year
Age
Sex
Site
Primary or secondary
Amyloid type
RA
HD
Diverticula
Surgical morbidity
Surgical mortality
1 2
Shinozaki Oda
1989 1990
66 65
M F
Sigmoid Sigmoid
Primary Secondary
AL AA
?
-
-
Arrhythmia Heart failure
Dead Dead
3
Hoshi
1991
55
F
Sigmoid
Secondary
?
?
-
-
?
?
4
Ishizaki
1991
60
M
Splenic
Primary
?
-
-
-
?
Alive
5
Nonaka
1992
72
F
Sigmoid
Secondary
?
?
-
-
?
?
6
Shimizu
1993
62
M
Rectum
Secondary
AA
-
?
-
–
Alive
7
Nishimoto
1993
74
F
Sigmoid
Secondary
?
?
-
-
Pneumonia
Dead
8
Ninomiya
1994
56
M
Sigmoid
Secondary
AL
-
?
-
?
?
9
Araki
1996
56
M
Sigmoid
Secondary
?
-
?
-
–
Alive
10
Sakashita
2000
53
M
Sigmoid
Familial
ATTR
-
-
-
11
Shindo
2000
55
F
Transverse
Secondary
AA
?
-
-
Infection
Dead
12
Shindo
2000
49
M
Splenic
Secondary
?
-
?
-
–
Alive
13
Orita
2001
54
M
Transverse
Secondary
?
-
?
-
?
?
14
Unemura
2001
71
F
Rectum
Secondary
AH
-
?
?
–
Alive
15
Toyama
2005
56
M
Sigmoid
Secondary
?
-
?
-
–
Alive
16
Araki
2006
73
M
Descending
Secondary
?
-
?
-
SSI
Dead
17 18
Umeda Wakai
2007 2007
76 75
M M
Sigmoid Sigmoid
Primary Primary
? ?
-
-
? -
SSI Pneumonia
Alive Alive
19
Hosotaki
2007
77
F
Descending
Secondary
?
?
?
-
MOF
Dead
20
Sakai
2008
60
M
Hepatic
Primary
AL
-
-
-
Abscess
Alive
21
Present case
62
F
Rectum
Secondary
AA
?
-
?
–
Alive
(Autopsy)
RA rheumatoid arthritis, HD hemodialysis, SSI surgical-site infection, MOF multiple organ failure
123
34
to RA and HD was noted in 7 (including the present case) and 9, respectively. Surgery was performed in 20 patients, and the remaining one underwent autopsy without surgical treatment. Diverticula of the colon were observed in 3 patients: one primary and two secondary amyloidosis cases, including the present case. Postoperative complications were observed in 9 (60.0%) of 15 who were described in the articles. Surgical mortality was observed in 6 (37.5%) of 16 who were described in the articles. All patients with surgical mortality showed postoperative complications. Five of the 6 cases of surgical mortality showed secondary amyloidosis, and four of the 5 had RA. Colorectal perforation with amyloidosis was relatively associated with poor prognosis, especially in secondary amyloidosis patients with RA. In conclusion, we report herein a case of perforation of a rectal diverticulum with amyloidosis secondary to RA. On the basis of reviewing the clinicopathologic features of the 21 reported patients, colorectal perforation with amyloidosis was associated with poor prognosis, especially in secondary amyloidosis patients with RA, although the present case underwent successful treatment for the perforation. Furthermore, in patients with amyloidosis, we should be careful regarding the management of constipation and colorectal diverticula. Acknowledgments We gratefully acknowledge Dr. Hikari Orita (Wakayama Medical University) and Dr. Shoji Hoshi (Shizuoka Saiseikai General Hospital) for their great contribution to this article.
References 1. Suzuki A, Ohosone Y, Obana M, Mita S, Matsuoka Y, Irimajiri S, et al. Cause of death in 81 autopsied patients with rheumatoid arthritis. J Rheumatol. 1994;21:33–6. 2. Nakamura T. Clinical strategies for amyloid A amyloidosis secondary to rheumatoid arthritis. Mod Rheumatol. 2008;18:109–18. 3. Cunnane G. Amyloid precursors and amyloidosis in inflammatory arthritis. Curr Opin Rheumatol. 2001;13:67–73. 4. Gilat T, Revach M, Sohar E. Deposition of amyloid in the gastrointestinal tract. Gut. 1969;10:98–104. 5. Tada S, Iida M, Iwashita A, Matsui T, Fuchigami T, Yamamoto T, et al. Endoscopic and biopsy findings of the upper digestive tract in patients with amyloidosis. Gastrointest Endosc. 1990; 36:10–4. 6. Kobayashi H, Tada S, Fuchigami T, Okuda Y, Takasugi K, Matsumoto T, et al. Secondary amyloidosis in patients with rheumatoid arthritis: diagnostic and prognostic value of gastroduodenal biopsy. Br J Rheumatol. 1996;35:44–9. 7. Thaler W, Schatzer G, Eder P, Fichtel G. Amyloidosis—an unusual case of recurrent intestinal bleeding and sigmoid perforation: case report with review of the literature. Int J Colorectal Dis. 1999;14:297–9. 8. Gilat T, Spiro HM. Amyloidosis and the gut. Am J Dig Dis. 1968;13:619–33. 9. Ishizaki Y, Nobori M, Tanaka N, Kanamori Y, Asada M, Saiki S. Perforation and tumor formation of the intestine in primary amyloidosis. Am J Gastroenterol. 1991;86:363–6.
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Clin J Gastroenterol (2010) 3:30–35 10. Gejyo F, Yamada T, Odani S, Nakagawa Y, Arakawa M, Kunitomo T, et al. A new form of amyloid protein associated with chronic hemodialysis was identified as b2-microgloburin. Biochem Biophys Res Commun. 1985;129:701–6. 11. Kuroda T, Tanabe N, Harada T, Murakami S, Hasegawa H, Sakatsume M, et al. Long-term mortality outcome in patients with reactive amyloidosis associated with rheumatoid arthritis. Clin Rheumatol. 2006;25:498–505. 12. Tada S, Iida M, Yao T. Intestinal pseudo-obstruction in patients with amyloidosis: clinicopathologic differences between chemical types of amyloid protein. Gut. 1993;34:1412–7. 13. Sakai T, Sato K, Tamura T, Tanaka M, Sudo Y. A case of primary amyloidosis found out with megacolon and perforation of the right-side colon (in Japanese with English abstract). Jpn J Gastroenterol Surg (Nihon Shokaki Geka Gakkai Zasshi). 2008;41:688–94. 14. Orita H, Kamimura M, Kitabata Y, Shiizaki K, Narukawa N, Abe T, et al. A case of long-term hemodialysis patient that showed the ileus concerned with the dialysis related amyloidosis (in Japanese). Kidney (Jinzou). 2001;23:70–3. 15. Stollman N, Raskin JB. Diverticular disease of the colon. Lancet. 2004;363:631–9. 16. Arsura EL. Corticosteroid-association perforation of colonic diverticula. Arch Intern Med. 1990;150:1337–8. 17. Tyau ES, Prystowsky JB, Joehl RJ, Nahrwold DL. Acute diverticulitis. A complicated problem in the immunocompromised patient. Arch Surg. 1991;126:855–8. 18. Mpofu S, Mpofu CMA, Hutchinson D, Maier AE, Dodd SR, Moots RJ. Steroids, non-steroidal anti-inflammatory drugs, and sigmoid diverticular abscess perforation in rheumatic conditions. Ann Rheum Dis. 2004;63:588–90. 19. Shinozaki S, Hongo M, Hirai K, Kawashima A, Hirayama J, Kobayashi T, et al. Perforation of sigmoid colon in primary amyloidosis: report of a case (in Japanese). J Jpn Soc Intern Med (Nippon Naika Gakkai Zasshi). 1989;78:1603–4. 20. Oda Y, Katsuki I, Najima K, Hayashi K, Hotokebuchi T, Sugioka Y, et al. A case of colonic perforation due to secondary amyloidosis associated with rheumatoid arthritis (in Japanese with English abstract). Kyushu J Rheumatol (Kyushu Riumachi). 1990;9:232–6. 21. Hoshi S, Asano E, Sugiyama H. An intestinal perforation case of rheumatoid arthritis complicated with secondary amyloidosis (in Japanese with English abstract). J.S.S.M (Shizuoka Saiseikai Sougobyoin Igaku Zasshi). 1991;9:71–6. 22. Nonaka S, Shiokawa S, Yasuda M, Shingu M, Watanabe D, Tashiro K, et al. Sigmoid colon perforation in a rheumatoid arthritis patient with secondary amyloidosis (in Japanese with English abstract). Kyushu J Rheumatol (Kyushu Riumachi). 1992;11:220–3. 23. Shimizu T, Yoshimatsu K, Mori M, Katou H, Endou S, Haga S, et al. A case report of rectal perforation occurring in a dialysisassociated amyloidosis (in Japanese with English abstract). J Jpn Soc Coloproctol (Nippon Daicho Komonbyo Gakkai Zasshi). 1993;46:768–71. 24. Nishimoto Y, Kimura K, Obata S, Maeda K, Araki K. A case of sigmoid colon perforation in a patient with secondary amyloidosis (in Japanese). Arch Intern Med (Naika). 1993; 71:360–2. 25. Ninomiya I, Nishimura G, Hashimoto H, Nonomura A. Two cases of gastrointestinal tract perforation in amyloidosis (in Japanese with English abstract). Jpn J Gastroenterol Surg (Nihon Shokaki Geka Gakkai Zasshi). 1994;27:2471–5. 26. Araki H, Muramoto H, Oda K, Koni I, Mabuchi H, Mizukami Y, et al. Severe gastrointestinal complications of dialysis-related amyloidosis in two patients on long-term hemodialysis. Am J Nephrol. 1996;16:149–53.
Clin J Gastroenterol (2010) 3:30–35 27. Sakashita N, Ando Y, Obayashi K, Terazaki H, Yamashita T, Takei M, et al. Familial amyloidotic polyneuropathy (ATTR Ser50Ile): the first autopsy case report. Virchows Arch. 2000; 463:345–50. 28. Shindo H, Ishikawa H, Mine Y, Yoshida K. Gastrointestinal amyloidosis causing perforation of the colon: report of two cases (in Japanese with English abstract). J Jpn Surg Assoc (Nihon Rinshogeka Gakkai Zasshi). 2000;61:702–5. 29. Unemura Y, Nojiri T, Ogawa M, Misawa T, Ikeuchi K, Yamazaki Y. A case rectal perforation in dialysis-related amyloidosis (in Japanese with English abstract). Jpn J Gastroenterol Surg (Nihon Shokaki Geka Gakkai Zasshi). 2001;34:142–5. 30. Toyama K, Kondo S, Tanaka K, Kimura K. Sigmoid colon perforation in a case with dialysis-related amyloidosis. St. Marianna Med J (Sei Marianna Ikadaigaku Zasshi). 2005;33:537–42.
35 31. Araki M, Ohsawa K, Takebe K, Shinoda Y. A case of intestinal amyloidosis with chronic renal failure (in Japanese). Gunma Igaku. 2006;84:163–6. 32. Umeda Y, Tanahashi S, Mizutani N, Gotoo M, Iida T. Sigmoid colon perforation associated with primary amyloidosis (in Japanese). J Clin Surg (Rinsho Geka). 2007;62:545–8. 33. Wakai A, Wakai T, Shirai Y, Ikeda Y, Nagahashi M, Hatakeyama K. Perforation of the sigmoid colon in a patient with intestinal amyloidosis: report of a case (in Japanese). Niigata Med J (Niigata Igakukai Zasshi). 2007;121:346–50. 34. Hosotaki K, Tabira Y, Shimamoto M. A case of colon perforation with pneumatosis cystoids intestinalis due to secondary amyloidosis (in Japanese with English abstract). J Jpn Surg Assoc (Nihon Rinshogeka Gakkai Zasshi). 2007;68:2811–6.
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CASE REPORT
Perforation of rectal diverticulum with amyloidosis secondary to rheumatoid arthritis: case report and review of the literature Daisuke Takeuchi • Naohiko Koide • Masato Kitazawa Kazuhiro Fukushima • Masayuki Matsuda • Mana Fukushima • Shinichi Miyagawa
•
Received: 6 September 2009 / Accepted: 22 November 2009 / Published online: 23 December 2009 Ó Springer 2009
Abstract We report a case of perforation of a rectal diverticulum with amyloidosis secondary to rheumatoid arthritis (RA), and review the clinicopathologic features in 21 Japanese amyloidosis patients with colorectal perforation. A 62-year-old woman with amyloidosis secondary to RA suddenly complained of abdominal pain. Computed tomography (CT) showed ascites and free air in the abdominal cavity, and many diverticula with calculi in the sigmoid colon. Emergent surgery was performed for acute peritonitis. We observed the perforation, 5 mm in diameter, of a diverticulum in the upper rectum, and many diverticula located in the upper rectum and sigmoid colon. Anterior resection of the rectum combined with sigmoidectomy was performed. The resected specimen showed many diverticula including fecaliths, approximately 7 mm in size. Histopathologically, many inflammatory cells had infiltrated around the perforation. On Congo red staining, amyloid deposits were observed in or around the small blood vessels of the lamina propria mucosa and submucosa of the rectum. Although colorectal perforation with amyloidosis secondary to RA is rare, this complication was associated with poor prognosis. Furthermore, in
D. Takeuchi N. Koide (&) M. Kitazawa S. Miyagawa Department of Surgery, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto 390-8621, Japan e-mail: [email protected] K. Fukushima M. Matsuda Department of Internal Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, Matsumoto, Japan M. Fukushima Department of Clinical Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, Japan
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patients with amyloidosis, we should be careful regarding the management of colorectal diverticula. Keywords Perforation Rectum Amyloidosis Rheumatoid arthritis Diverticula
Introduction Rheumatoid arthritis (RA) can occasionally complicate the development of reactive or secondary amyloidosis, which shows the deposition of amyloid A in several organs, and this complication can lead to a high risk of organ failure and mortality [1, 2]. Amyloid A fibrils originate from a fragment of serum amyloid A protein [3]. Chronic inflammatory conditions, of which the foremost is RA, develop and stimulate amyloid A amyloidosis in several organs [2]. Amyloidosis frequently involves the gastrointestinal (GI) tract [4, 5]. Reactive amyloidosis secondary to RA is also frequently observed in the GI tract, and the histological diagnosis is based on endoscopic biopsy tissues of the GI tract [6]. On the other hand, acute abdominal complications, including hemorrhage, pseudo-obstruction, and GI tract perforation, are uncommon in patients with amyloidosis; however, the clinical outcome in amyloidosis patients with perforation of the GI tract, including both the upper and lower tracts, has been poor [7]. Perforation of the colon and rectum has exceptionally been reported in patients with amyloidosis, and rectal perforation was reported in a few cases with amyloidosis [8, 9]. However, in amyloidosis patients secondary to RA with colorectal perforation, the clinicopathologic features and outcome are not yet well known. We report herein a case of perforation of a rectal diverticulum with amyloidosis secondary to RA, and
Clin J Gastroenterol (2010) 3:30–35
review and discuss the clinicopathologic features and outcomes in 21 Japanese amyloidosis patients with colorectal perforation reported over the last two decades.
Case report A 62-year-old woman, who was admitted for the initiation of hemodialysis, suddenly complained of severe abdominal pain. From 16 years ago, the patient has been treated for RA with prednisolone. Nine years ago, a gastric polyp was detected by esophagogastroscopy, and biopsy specimens taken from the polyp histologically showed amyloid A deposition. Furthermore, amyloid deposits were histologically noted in biopsy specimens taken from the right kidney because of renal dysfunction, which has not been associated with hemodialysis (HD), and secondary amyloidosis associated with RA was diagnosed. Recently, the patient complained of constipation. Physical examination showed a 37.9°C temperature, tachycardia, and severe tenderness with muscle defense of the lower abdomen. Blood examination showed leukocytosis (15,270/ll) with neutrophilia (97.9%), and blood chemistry revealed elevated serum levels of C-reactive protein (14.2 mg/dl), blood urea nitrogen (114.0 mg/dl), and creatinine (4.38 mg/dl). Blood gas analysis identified severe metabolic acidosis (base excess; -14.3 mmol/l), hypoxia (66.8 mmHg), and hypocarboxia (23.4 mmHg). Computed tomography (CT) showed the presence of ascites and free air in the abdominal cavity (Fig. 1a), and many diverticula with intestinal calculi in the sigmoid colon (Fig. 1b). Emergent surgery was performed for acute peritonitis suspected to have been caused by colonic perforation. On laparotomy, we observed dirty ascites (3,100 ml), and the perforation of a diverticulum in the upper rectum 3 cm above the peritoneal turning of Douglas pouch (Fig. 2). Many diverticula were located in the upper rectum and sigmoid colon. However, neither acute ischemic nor congestive findings of the rectum or sigmoid colon were observed. Each diverticulum included a hard stone-like substance, a so-called intestinal calculus or fecalith. We
31
conducted anterior resection of the rectum combined with sigmoidectomy, and performed a colostomy (Hartmann’s procedure). The diverticula were included in the resected colorectum. The patient was immediately admitted to the intensive care unit after surgery for emergent hemodialysis and endotoxin-absorption therapy using a column of polymyxin B-immobilized fibers, but the postoperative course was uneventful. Macroscopically, the perforation was 5 mm in diameter on the tenial side of the upper rectum (Fig. 3a). The resected specimen showed many diverticula (Fig. 3b), and a fecalith, approximately 7 mm in size, was included in each diverticulum. The colonic wall of these diverticula seemed to be very thin, and we could observe these fecaliths through the thin colonic wall (Fig. 3c). Neither acute ischemic nor congestive finding of the resected specimen were observed. Histopathologically, many inflammatory cells had infiltrated around the perforation (Fig. 4a, b). Congo-red-stained amyloid (pink-red deposit) was observed in the stroma of the lamina propria mucosa and submucosa of the rectum, especially in or around the small blood vessels (Fig. 4c, d). Furthermore, narrow blood vessel lumens caused by amyloid deposition were occasionally observed.
Discussion Amyloidosis, including primary and secondary diseases, frequently progresses to several organ disorders due to abnormal extracellular amyloid deposition. In patients undergoing HD, the frequency of secondary amyloidosis has increased [10]. In secondary amyloidosis patients associated with RA, the initiation of HD for end-stage renal disease leads to poor survival [11]. In the present patient, RA has been treated for 16 years, and amyloid deposits have been evidenced using gastric and renal biopsy specimens. HD has not yet been performed, although it is scheduled in the near future. Therefore, the present patient was considered to show secondary amyloidosis associated with RA.
Fig. 1 Abdominal CT findings. a CT shows peritoneal ascites (arrowheads) and free air (arrow) in the abdominal cavity. b CT shows many diverticula of the sigmoid colon, and the diverticula include an intestinal calculus
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Fig. 2 Operative findings. The arrow shows a perforation of the upper rectum, with a diameter of 5 mm. However, the rectum and sigmoid colon show no acute ischemia or congestion
Fig. 3 Macroscopic findings. a A perforation (arrow) was detected in the upper rectum, and the diverticula were completely resected in the upper rectum and sigmoid colon. b The mucosal side. Arrowheads show many diverticula in the upper rectum and sigmoid colon. c The serosal side. Arrowheads show many diverticula, and the fecaliths are covered with the thin colon wall
In GI amyloidosis, colorectal perforation has been exceptional, and this complication has been explained by several factors. Amyloid deposition in the GI tract was frequently observed in or around the wall of blood vessels in the lamina propria mucosa and submucosa [4], and amyloid A deposits were observed in the small blood vessels of the submucosa of the GI tract in patients with secondary amyloidosis [12], such as in the present case. As a reason for intestinal perforation, it is well known that amyloid deposition can lead to occlusion of blood vessels or their luminal narrowing, and can result in local ischemia of the GI wall. Consequently, these factors cause GI tract perforation. In the present case, amyloid deposits were observed in the small blood vessels of the lamina propria mucosa and submucosa of the rectum and sigmoid colon. Narrowing of the blood vessel lumens by amyloid deposition, which can lead to weakening of the intestinal wall,
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was also observed. Several types of mechanism of intestinal perforation associated with amyloidosis have been considered, but are not sufficiently understood. As another type of intestinal perforation in patients with amyloidosis, megacolon caused by amyloid deposits in the proper muscle layer has been considered [13]. In the present case, this finding was not observed. Furthermore, Orita et al. [14] reported a case of HD-related amyloidosis with colonic perforation due to ileus. It was noted that this perforation occurred in the rectal diverticulum, and many diverticula containing fecaliths were observed. Amyloid deposition occurs in paralysis of the intestine, and clinically results in constipation. Gastrointestinal neuropathy associated with amyloid deposition in the autonomic nerves has been observed in amyloidosis patients with intestinal pseudo-obstruction [12]. Furthermore, Stollman and Raskin [15] described increased intracolonic pressures in patients with diverticulosis. It was straightforward to consider that the presence of many diverticula and fecaliths occurs due to constipation. The diverticulitis occurred due to fecalith presence, and the perforation of the rectal diverticulum may have resulted in the present case. Therefore, in patients with amyloidosis, we should be careful regarding the management of constipation and colorectal diverticula. In addition, we noted steroid-associated diverticulitis and perforation of the GI tract. The present RA patient has undergone long-term prednisolone treatment. Arsura [16] described a relationship between colonic diverticula perforation and corticosteroid use, and Tyau et al. [17] reported that diverticular perforation was frequently observed in immunocompromised patients, including those using steroids. Furthermore, corticosteroid treatment showed a close association with sigmoid diverticular abscess perforation under rheumatic conditions [18]. Therefore, the perforation in this case may be explained by several factors, including secondary amyloid deposition of the colorectum, and diverticulitis caused by fecaliths associated with long-term steroid treatment for RA. Twenty Japanese amyloidosis patients with colorectal perforation, identified by searching PubMed and Japana Centra Revuo Medicina, were reported in the last decade (between 1989 and 2008), excluding supplements. A review of the clinicopathologic features of the 21 patients [9, 13, 14, 19–34], including the present case, is summarized in Table 1. The gender ratio (man/woman) was 1.63, and the mean age of these cases was 63 years. Regarding the site of perforation, the most common site was the sigmoid colon, and 85.7% of perforations were observed in the left colon. Rectal perforation was observed in 3 patients, including the present case (14.3%). Primary amyloidosis was observed in 6, while secondary amyloidosis was observed in 15 (71.4%). Amyloidosis secondary
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Fig. 4 Histopathologic findings. a Hematoxylin and eosin (HE) staining of the perforated diverticulum (920). The upper area of the photograph shows the luminal side of the rectum. The central part shows the perforated site. b HE staining of the lamina propria mucosa and submucosa near the perforated diverticulum (9200). Inflammatory cells infiltrating the stroma of the diverticulum are observed in or around the small blood vessels. c Congo red staining of the perforated diverticulum (920). The photograph was taken using a serial section to that of a. d Congo red staining of the lamina propria mucosa and submucosa near the perforated diverticulum (9200). Congored-stained amyloid (pink–red deposit) is observed in or around the small blood vessels (color figure online)
Table 1 Amyloidosis patients with colorectal perforation reported over the last two decades Case
Author
Year
Age
Sex
Site
Primary or secondary
Amyloid type
RA
HD
Diverticula
Surgical morbidity
Surgical mortality
1 2
Shinozaki Oda
1989 1990
66 65
M F
Sigmoid Sigmoid
Primary Secondary
AL AA
?
-
-
Arrhythmia Heart failure
Dead Dead
3
Hoshi
1991
55
F
Sigmoid
Secondary
?
?
-
-
?
?
4
Ishizaki
1991
60
M
Splenic
Primary
?
-
-
-
?
Alive
5
Nonaka
1992
72
F
Sigmoid
Secondary
?
?
-
-
?
?
6
Shimizu
1993
62
M
Rectum
Secondary
AA
-
?
-
–
Alive
7
Nishimoto
1993
74
F
Sigmoid
Secondary
?
?
-
-
Pneumonia
Dead
8
Ninomiya
1994
56
M
Sigmoid
Secondary
AL
-
?
-
?
?
9
Araki
1996
56
M
Sigmoid
Secondary
?
-
?
-
–
Alive
10
Sakashita
2000
53
M
Sigmoid
Familial
ATTR
-
-
-
11
Shindo
2000
55
F
Transverse
Secondary
AA
?
-
-
Infection
Dead
12
Shindo
2000
49
M
Splenic
Secondary
?
-
?
-
–
Alive
13
Orita
2001
54
M
Transverse
Secondary
?
-
?
-
?
?
14
Unemura
2001
71
F
Rectum
Secondary
AH
-
?
?
–
Alive
15
Toyama
2005
56
M
Sigmoid
Secondary
?
-
?
-
–
Alive
16
Araki
2006
73
M
Descending
Secondary
?
-
?
-
SSI
Dead
17 18
Umeda Wakai
2007 2007
76 75
M M
Sigmoid Sigmoid
Primary Primary
? ?
-
-
? -
SSI Pneumonia
Alive Alive
19
Hosotaki
2007
77
F
Descending
Secondary
?
?
?
-
MOF
Dead
20
Sakai
2008
60
M
Hepatic
Primary
AL
-
-
-
Abscess
Alive
21
Present case
62
F
Rectum
Secondary
AA
?
-
?
–
Alive
(Autopsy)
RA rheumatoid arthritis, HD hemodialysis, SSI surgical-site infection, MOF multiple organ failure
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34
to RA and HD was noted in 7 (including the present case) and 9, respectively. Surgery was performed in 20 patients, and the remaining one underwent autopsy without surgical treatment. Diverticula of the colon were observed in 3 patients: one primary and two secondary amyloidosis cases, including the present case. Postoperative complications were observed in 9 (60.0%) of 15 who were described in the articles. Surgical mortality was observed in 6 (37.5%) of 16 who were described in the articles. All patients with surgical mortality showed postoperative complications. Five of the 6 cases of surgical mortality showed secondary amyloidosis, and four of the 5 had RA. Colorectal perforation with amyloidosis was relatively associated with poor prognosis, especially in secondary amyloidosis patients with RA. In conclusion, we report herein a case of perforation of a rectal diverticulum with amyloidosis secondary to RA. On the basis of reviewing the clinicopathologic features of the 21 reported patients, colorectal perforation with amyloidosis was associated with poor prognosis, especially in secondary amyloidosis patients with RA, although the present case underwent successful treatment for the perforation. Furthermore, in patients with amyloidosis, we should be careful regarding the management of constipation and colorectal diverticula. Acknowledgments We gratefully acknowledge Dr. Hikari Orita (Wakayama Medical University) and Dr. Shoji Hoshi (Shizuoka Saiseikai General Hospital) for their great contribution to this article.
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