Digestive Endoscopy 2013; 25: 622–625
doi: 10.1111/j.1443-1661.2012.01398.x
Case Report
Diffuse gastroduodenitis associated with ulcerative colitis: Treatment by infliximab Mitsuro Chiba,1 Iwao Ono,2 Hideki Wakamatsu,3 Isao Wada4 and Katsuhiko Suzuki5 1
Division of Gastroenterology and 2Department of Pathology, Nakadori General Hospital, 3Wakamatsu Naika Clinic, 4Division of Gastroenterology, Akita Kumiai General Hospital, and 5Division of Surgery, Honjo Daiichi Hospital, Akita, Japan
Diffuse gastroduodenitis resembling ulcerative colitis in respect to macro- and microscopic findings occurs in ulcerative colitis, although it is rare. Reports of gastroduodenitis associated with ulcerative colitis treated with infliximab are rare. A 58-year-old man had tarry stool in March 2011. He had a history of ulcerative colitis that was diagnosed in 1984. He underwent subtotal colectomy in 1991. Endoscopy and radiography revealed diffuse friable mucosa throughout the duodenum and an ulcer in the middle of the descending portion, resulting in a narrow portion.
INTRODUCTION
T
HE CHARACTERISTIC FORM of intestinal lesion is continuous for ulcerative colitis (UC) while discontinuous or skipped for Crohn’s disease (CD). In addition, UC affects only the large bowel except for backwash ileitis and pouchitis, whereas CD affects the entire digestive tract. Advancements in gastroenterology have modified the above principal. Now, it is widely accepted that a skip lesion occurs in ulcerative colitis: an appendiceal orifice inflammation is present with intervening normal mucosa in distal ulcerative colitis. Diffuse inflammation in the upper gastrointestinal tract in UC was first reported in 1960.1 Since then, additional case reports and case series have been published.2–9 Characteristics of these lesions are summarized as follows. Macroscopic and microscopic findings are similar to bowel lesions in UC. They do not respond to anti-ulcer drugs, such as H2-blockers and proton pump inhibitors, but respond to the same treatment for UC. They are different from other lesions, including CD. The most common site affected is the duodenum followed by the stomach. The jejunum can also be affected in continuous form
Corresponding: Mitsuro Chiba, Division of Gastroenterology, Nakadori General Hospital, 3-15, Misono-cho, Minami-dori, Akita 010-8577, Japan. Email:
[email protected] Received 5 August 2012; accepted 6 September 2012.
bs_bs_banner
622
In the stomach, numerous small aphthae were observed in the antrum. Biopsy specimens of the duodenum and antrum showed marked inflammatory cell infiltration in both areas and cryptitis in the duodenum. Standard induction therapy of infliximab was started in April. The ulcer in the descending portion became a scar without diffuse mucosal friability in September 2011. Key words: complication, duodenitis, infliximab, ulcerative colitis.
as well as the ileum. In the present case report, we follow the naming (gastroduodenitis associated with UC [GDUC]) described by Hori et al.6 Biologics revolutionized treatment in inflammatory bowel disease (IBD). Infliximab has been shown to be effective not only in CD, but also in UC, including pouchitis.10,11 Here we report a case of GDUC with tarry stool that occurred 20 years after subtotal colectomy for UC. The GDUC was successfully treated with infliximab.
CASE REPORT
A
58-YEAR-OLD MAN had tarry stool on 11 March, 2011 and visited a local clinic. Esophagogastroduodenoscopy (EGD) revealed diffuse friable mucosa in the duodenum and an ulcer with a blood clot at the superior duodenal angulus (Fig. 1A). Proton pump inhibitor, sodium rabeprazole 10 mg/day, and mesalazine 3.0 g/day were given. Blood transfusion was not needed. However, endoscopy revealed no improvement. There was a large ulcer in the site just distal to the duodenal papilla. Therefore, he was referred and was admitted to Nakadori General Hospital on 4 April. His past and family histories were non-contributory, except for UC. In 1984, there was an onset of UC. In 1991, he underwent subtotal colectomy. In 1992, closure of ileostomy and ileorectal anastomosis were carried out. There was no medication being provided for ulcerative colitis when the tarry stool developed.
© 2012 The Authors Digestive Endoscopy © 2012 Japan Gastroenterological Endoscopy Society
Digestive Endoscopy 2013; 25: 622–625
GDUC treated by infliximab 623
Figure 1 Esophagogastroduodenoscopy (EGD) on (A) 14 March, 2011, (B,C) 5 April and (E) 13 September and (D) double-balloon enteroscopy on 21 April. Diffuse continuous friable mucosa was observed in the duodenum. (A) At the superior duodenal angulus, a white coating with a linear blood clot (arrow) was seen. (B) In the site just distal to the duodenal papilla, a narrowing of the duodenal lumen at the site of the ulcer (arrows) was seen. (C) Numerous small aphthae (white punctum with red halo, arrows) were densely observed in the antrum on 5 April. (D) Diffuse continuous friable mucosa was observed at the end of the duodenum. (E) By September 13 the ulcer was a scar. Diffuse mucosal friability was no longer observed.
There were no obvious symptoms of UC at the time of admission to our hospital. His bodyweight was 54.7 kg. No tenderness was found in the abdomen. Laboratory data showed mild or moderate abnormality as follows: hemoglobin 11.4 g/dL, total protein 6.1 g/dL, albumin 3.1 g/dL, choline esterase 195 IU/L (normal range 203–430 IU/L), a2 globulin 9.9% (normal range 4.8–8.6%), C-reactive protein (CRP) 0.7 mg/dL. Total cholesterol was normal (166 mg/ dL). Urinary anti-Helicobacter pylori antibody was negative. EGD revealed continuous diffuse friable mucosa in the descending portion of the duodenum with loss of Kerckring’s folds. At the middle of the descending portion, there was a semi-circumferential ulcer with luminal narrowing (Fig. 1B). Numerous small aphthae were observed in the antrum (Fig. 1C). Biopsy specimens of the duodenum showed marked inflammatory cell infiltration and cryptitis (Fig. 2). Those from the antrum showed similar cell infiltration. Neither granuloma nor immunohistochemically positive cells for cytomegalovirus were found in these specimens. Duodenography (Fig. 3) and enteroclysis showed diffuse inflammation up to the end of the duodenum. The double-balloon enteroscope and an overtube could pass through the narrow portion in the duodenum. The double-balloon enteroscopy confirmed diffuse inflammation up to the end of the duodenum (Fig. 1D). A diagnosis of GDUC was made. Colonoscopy showed mild mucosal cloudiness in the rectum and the
Figure 2 Microscopic findings of biopsy specimens of the duodenum showing marked inflammatory cell infiltration and cryptitis (¥ 200).
pouch. Standard induction therapy of infliximab (300 mg infusion at 0, 2nd and 6th weeks) was given on 11 April, 25 April, and 26 May, respectively. After the 2nd-week infusion of infliximab he was discharged. During hospitalization, the patient was provided a semi-vegetarian diet of 2000 kcal/day and the patient and his wife were provided dietary guid-
© 2012 The Authors Digestive Endoscopy © 2012 Japan Gastroenterological Endoscopy Society
624
M. Chiba et al.
Figure 3 Duodenography on 7 April, 2011. A narrow portion in the middle of the descending portion of the duodenum was evident. An uneven duodenal outline with micro-specula (arrows) and loss of Kerckring’s folds were seen. Aphthae were depicted in the antrum (arrowheads).
ance.12,13 On discharge he was advised to continue the semivegetarian diet and his prescribed medication was limited to sodium ferrous citrate at 50 mg/day every other day. CRP normalized on 18 April. Normalization of other laboratory test results occurred gradually in the following order: choline esterase in May, a2 globulin in July, total protein, albumin, and hemoglobin in September 2011. Numerous aphthae in the antrum disappeared by 26 April. The ulcer in the descending portion was in the healing stage and the narrowing of the lumen improved in May. The ulcer became a scar by September (Fig. 1E) and diffuse mucosal friability was no longer observed. The patient has remained well and no relapse of GDUC has been observed up to the present time (June 2012). Colonoscopy of the rectum and the pouch following infliximab therapy was not carried out because only mild mucosal cloudiness was observed in these areas at admission.
DISCUSSION
A
PHTHAE OBSERVED IN the antrum in the present case is one of the typical endoscopic appearances of GDUC.6 Hori et al. carried out EGD on 250 UC patients (pancolitis 163, left-sided colitis 60, proctosigmoiditis 27: patients with and without colectomy 162 and 88, respectively)
Digestive Endoscopy 2013; 25: 622–625
and found GDUC in 19 patients (7.6%).6 The study showed that GDUC was seen only in cases with pancolitis or in cases with proctocolectomy. The risk factors for developing GDUC were the presence of pancolitis and a lower dose of prednisolone but postoperative status was not a risk factor.6 A variety of symptoms are described in GDUC: nausea, vomiting, epigastralgia, fever, loose stool, and tarry stool. However, GDUC does not always cause symptoms. In the study by Hisabe et al., more than half of GDUC cases (9/15 cases) were asymptomatic.8 Efficacy of treatment for GDUC in Japanese reported cases was as follows: 5-aminosalicylic acid 38% (6 of 16 cases), prednisolone 45% (9/20), steroid pulse or semi-pulse therapy 78% (7/9).5 Although the prognosis of GDUC is generally fair, serious complications and even a death have been reported.3 They included massive hemorrhage,1,3,5 stenosis,2 perforation,7 and pancreatitis,2 some of which required surgery.2 A flare in gastroduodenal lesions associated with a reduction in steroid use is often similarly observed in UC.4,8 Due to faster induction of remission, fewer side-effects, and no concern with steroid dependency, we used infliximab for the present case rather than corticosteroid. Akitake et al. first described a GDUC case successfully treated by infliximab.9 We also found that infliximab was effective for GDUC. We usually limit the use of infliximab for induction of remission. Our test cases demonstrated that a semi-vegetarian diet can prevent relapse of CD far better than scheduled maintenance infliximab therapy.12,13 Advancements in IBD genetics enhances our understanding of the pathogenesis of bowel disease.14 Susceptibility genes identified in IBD are related to immunoregulation. IBD is thought to result from an inappropriate response of the mucosal immune system to gut microflora. Therefore, sites exposed to microbial agents are target sites for inflammation. Culturable and non-culturable bacteria and other microbial agents are present in the small intestine and stomach.15 The similar macroscopic and microscopic appearances and responses to drugs in GDUC to those of proctocolonic lesions in UC suggest that a similar pathogenesis is operating in GDUC.
CONFLICT OF INTERESTS
A
UTHORS DECLARE NO conflict of interests for this article.
REFERENCES 1 Thompson JW 3rd, Bargen JA. Ulcerative duodenitis and chronic ulcerative colitis: report of two cases. Gastroenterology 1960; 38: 452–5.
© 2012 The Authors Digestive Endoscopy © 2012 Japan Gastroenterological Endoscopy Society
Digestive Endoscopy 2013; 25: 622–625
GDUC treated by infliximab 625
2 Mitomi H, Atari E, Uesugi H, Nishiyama Y, Igarashi M, Arai N. Distinctive diffuse duodenitis associated with ulcerative colitis. Dig. Dis. Sci. 1997; 42: 684–93. 3 Annese V, Caruso N, Bisceglia M et al. Fatal ulcerative panenteritis following colectomy in a patient with ulcerative colitis. Dig. Dis. Sci. 1999; 44: 1189–95. 4 Shimura T, Inukai M, Yoshioka N et al. A case of diffuse gastritis and duodenitis associated with ulcerative colitis. Jpn. J. Gastroenterol. 2006; 103: 30–6 (in Japanese with an English abstract). 5 Nakajima M, Nakashima H, Kiyohara K et al. A case of diffuse duodenitis and enteritis following total colectomy for ulcerative colitis. Jpn. J. Gastroenterol. 2008; 105: 382–90 (in Japanese with an English abstract). 6 Hori K, Ikeuchi H, Nakano H et al. Gastroduodenitis associated with ulcerative colitis. J. Gastroenterol. 2008; 43: 193–201. 7 Corporaal S, Karrenbeld A, van der Linde K, Voskuil JH, Kleibeuker JH, Dijkstra G. Diffuse enteritis after colectomy for ulcerative colitis: two case reports and review of the literature. Eur. J. Gastroenterol. Hepatol. 2009; 21: 710–5. 8 Hisabe T, Matsui T, Miyaoka M et al. Diagnosis and clinical course of ulcerative gastroduodenal lesion associated with ulcerative colitis. Dig. Endosc. 2010; 22: 268–74.
9 Akitake R, Nakase H, Tamaoki M, Ueno S, Mikami S, Chiba T. Modulation of Th1/Th2 balance by infliximab rescues postoperative occurrence of small-intestinal inflammation associated with ulcerative colitis. Dig. Dis. Sci. 2010; 55: 1781–4. 10 Huang X, Lv B, Jin HF, Zhang S. A meta-analysis of the therapeutic effects of tumor necrosis factor-a blockers on ulcerative colitis. Eur. J. Clin. Pharmacol. 2011; 67: 759–66. 11 Barreiro-de Acosta M, García-Bosch O, Souto R et al. Efficacy of infliximab rescue therapy in patients with chronic refractory pouchitis: a multicenter study. Inflamm. Bowel Dis. 2012; 18: 812–7. 12 Chiba M, Abe T, Tsuda H et al. Lifestyle-related disease in Crohn’s disease: relapse prevention by a semi-vegetarian diet. World J. Gastroenterol. 2010; 16: 2484–95. 13 Chiba M, Tsuda H, Abe T, Sugawara T, Morikawa Y. Missing environmental factor in inflammatory bowel disease: diet-associated gut microflora. Inflamm. Bowel Dis. 2011; 17: E82–3. 14 Thompson AL, Lees CW. Genetics of ulcerative colitis. Inflamm. Bowel Dis. 2011; 17: 831–48. 15 Cotter PD. Small intestine and microbiota. Curr. Opin. Gastroenterol. 2011; 27: 99–105.
© 2012 The Authors Digestive Endoscopy © 2012 Japan Gastroenterological Endoscopy Society