Clin J Gastroenterol (2013) 6:111–115 DOI 10.1007/s12328-013-0360-7
CASE REPORT
Small intestinal perforation caused by cytomegalovirus reactivation after subtotal colectomy for ulcerative colitis: report of a case Hiroyuki Fujikawa • Toshimitsu Araki • Tadanobu Shimura • Yoshiki Okita Koji Tanaka • Mikihiro Inoue • Mikio Kawamura • Yasuhiro Inoue • Yasuhiko Mohri • Keiichi Uchida • Masato Kusunoki
•
Received: 22 November 2012 / Accepted: 15 January 2013 / Published online: 15 February 2013 Ó Springer Japan 2013
Abstract A 79-year-old woman with bloody diarrhea was diagnosed with ulcerative colitis. She developed intestinal perforation after high-dose steroid therapy. An emergency laparotomy revealed a perforation in the ascending colon, and a subtotal colectomy was performed with an ileostomy and a mucous fistula in the sigmoid colon. Histological findings of the resected colon showed the presence of cytomegalovirus in the endothelial cells of vessels around the ulcer floor. Twelve days after the laparotomy, she developed an ileal perforation with a bloody discharge from the ileostomy and underwent an emergency laparotomy. Multiple intestinal perforations were found in the ileum, and the perforated ileum was resected. Cytomegalovirus infection was controlled with ganciclovir postoperatively. Histological findings of the resected ileum showed the presence of cytomegalovirus in the endothelial cells of vessels around the ulcer floor. This is the first report of ileal perforation due to cytomegalovirus infection confirmed pathologically in a patient with ulcerative colitis.
Increased risk for reactivation of cytomegalovirus (CMV) disease in patients with ulcerative colitis (UC) compared to the general population is thought to be due to both iatrogenic and inherent factors [1]. One of the risk factors is that patients are immunocompromised with the use of immunosuppressive agents such as corticosteroids, cyclosporine, azathioprine, and infliximab [1, 2]. CMV colitis is frequently found in immunocompromised patients with severe UC and may require surgical treatment because of the development of large bowel perforation. Ileal perforation due to CMV infection confirmed pathologically in patients with UC has not been reported though there are reports of several diseases with immunocompromised status [3–10]. We herein report a case of ileal perforation associated with CMV reactivation confirmed pathologically after a subtotal colectomy for large bowel perforation with CMV colitis in a UC patient.
Keywords Cytomegalovirus Perforation Ileum Ulcerative colitis
Case report
H. Fujikawa (&) T. Araki T. Shimura Y. Okita K. Tanaka M. Inoue M. Kawamura Y. Inoue Y. Mohri K. Uchida M. Kusunoki Division of Reparative Medicine, Department of Gastrointestinal and Pediatric Surgery, Institute of Life Sciences, Mie University Graduate School of Medicine, 2-174, Edobashi, Tsu, Mie 514-8507, Japan e-mail: [email protected]
A 79-year-old woman newly diagnosed with UC 1 month earlier was admitted to a nearby hospital for evaluation of elevated fever and exacerbations of abdominal pain and diarrhea. Colonoscopy revealed an edematous, granular mucosa with small erosions on the day of admission and, a few days later, an extended ulcerative lesion. These findings were consistent with severely active UC, and prednisolone (PSL) at 50 mg/day was begun. The PSL dosage was gradually reduced to 25 mg/day because her symptoms appeared to improve. However, her symptoms became exacerbated again, and the PSL dosage was increased to 40 mg/day. Another colonoscopy revealed a punched-out
Introduction
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ulcer with bleeding (Fig. 1a). A few days later, a blood test for CMV antigenemia was positive, and she was treated with antiviral therapy and a decreased dosage of PSL. Her symptoms did not improve in spite of additional treatment with cytapheresis. She developed severe abdominal pain 54 days after admission, and abdominal computed tomography (CT) showed free air. She was transferred to our hospital for surgical treatment with a diagnosis of intestinal perforation. One site of bowel perforation was found at the cecum, and we performed a subtotal colectomy with end ileostomy and mucous fistula formation in the sigmoid colon. Grossly, the surgical specimen demonstrated lesions of wide mucous ulceration with several pseudopolypoid formations in the pan-colon and perforation in the cecum. The pathological findings showed areas of preserved mucosa with marked inflammatory changes, mainly cryptal distortion, with superficial lymphangiectasia and lymphoplasmacytic infiltration of the lamina propria. Also present were several eosinophils and neutrophils, which spread transmurally, mainly in the ulcerated lesions. Inclusion bodies were present in histological findings (Fig. 1b) and immunohistochemical staining for CMV showed a positive reaction in endothelial cells of vessels around the ulcer floor (Fig. 1c). The diagnosis was Fig. 1 Preoperative endoscopic findings of the colon and histological findings of the resected colon. a Colonoscopy revealed punched-out ulcerations with deep floors in the transverse colon. b Histology showed inclusion bodies (arrow). c Immunohistochemical staining was performed by antibodies against cytomegalovirus, and inclusion bodies were stained in the cytoplasm of endothelial cells (arrows)
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confirmed as a large bowel perforation due to CMV colitis with UC. After surgery, the patient’s condition improved with polymyxin B-immobilized fiber column (PMX) hemoperfusion and continuous hemodiafiltration, and without antiviral therapy. Twelve days after the laparotomy, she developed a bloody discharge from the ileostomy with low-grade fever, leukocytosis and mild elevation of serum C-reactive protein. Abdominal pain and tenderness were unclear because of the condition under mild sedation. Endoscopy revealed ulcerations with deep floors in the ileum 8 and 12 cm from the end of the ileostomy (Fig. 2a) and we investigated only up to the lumen with the ulcerations. CT showed free air around the stoma site, and we performed an emergency operation with the diagnosis of small bowel perforation. Operative findings showed two ileal perforations in the ileum that matched the sites of ulceration in the endoscopic findings. The ileum from the open end of stoma to the perforated lesion was resected (Fig. 2b), and an end-ileostomy was reconstructed. We did not find other pathological lesions in the serous surface of the small intestine and the ileal lumen near the resection stump. Immunohistological findings of the resected ileum showed CMV inclusion in the endothelial cells of vessels around the ulcer floor (Fig. 2c).
Clin J Gastroenterol (2013) 6:111–115
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Fig. 2 Preoperative endoscopic findings, gross appearance of the resected small bowel, and histological findings. a Endoscopy revealed ulcerations with punched-out lesions and bleeding. b The surgical specimen showed deep ulcerations with two perforative lesions (arrow). c Inclusion bodies were stained in the cytoplasm of endothelial cells by immunohistochemistry
The diagnosis was confirmed as multiple ileal perforations due to CMV ileitis. In addition, a blood test for CMV antigenemia after surgery was positive. After surgery, we administered ganciclovir for CMV reactivation and performed PMX hemoperfusion for endotoxin removal. She did not develop a bloody discharge from the ileostomy after surgery and we confirmed that a blood test for CMV antigenemia was negative on postoperative day 10. Although a postoperative wound infection and exacerbation of chronic heart failure due to dilated cardiomyopathy developed, her condition improved and she was transferred to another hospital for continued treatment. She was discharged 5 months after her primary surgery, remains asymptomatic, and is undergoing no specific treatment.
Discussion CMV is a member of the Herpesviridae family. It generally infects 40–100 % of healthy individuals [11], and primary CMV infection is acquired early in life. Although CMV infections are commonly asymptomatic, they can produce a mild mononucleosis-like syndrome [12]. CMV disease can occur in various organs, such as the lung, liver, gastrointestinal tract, retina, and brain [13]. The most common site in
the gastrointestinal tract is the colon; CMV infection can occur anywhere from the esophagus to the rectum [3]. Gastrointestinal involvement in CMV infection may comprise vasculitis in the affected segment, resulting in ischemia and infarction [14]. CMV infections are generally reactivated in patients who are immunocompromised due to factors such as acquired immunodeficiency syndrome (AIDS), organ transplants, malignant tumors, chemotherapy, and immunosuppressive medications [15]. CMV enterocolitis has been reported in both older immunocompetent hosts and immunocompromised hosts [4, 16, 17]. This shows an age-related dysfunction of the immune system, which may weaken with age; the perturbation of mucosal immunity can predispose these patients to development of various infectious and inflammatory diseases [16, 17]. A meta-analysis of the outcome of CMV colitis in immunocompetent hosts showed that most patients were older than 55 years and showed comorbidities (77.3 %) [18]. Severe, steroid-refractory UC especially occurs together with CMV colitis [2, 19], and such patients are usually treated with immunosuppressive medications. Systemic steroid therapy is the gold standard in management of acute moderate to severe flare-ups of UC [2], and steroidrefractory patients require rescue therapies such as immunosuppressive agents [20]. These treatments have been
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associated with an increased risk of CMV colitis in UC [2]. A prospective study reported that CMV reactivation was only observed in patients on systemic steroid therapy, not in patients with active UC before starting steroid therapy [21]. In addition, patients with severe and steroid-refractory UC are likely to undergo a colectomy, and CMV infection has been confirmed in 19 % of patients who have undergone colectomies [22]. Interestingly, Matsuoka et al. [21] reported that antiviral therapies should not be necessary for most UC patients with only CMV reactivation as long as the CMV antigen values are low, while the efficacy of ganciclovir in CMV infection has been widely recognized. In CMV colitis, the necessity for antiviral therapy after colectomy has been unclear except in cases of CMV disease in other organs because most of the colon with CMV infection was resected, and therefore the patient was not treated with antiviral therapy. However, antiviral therapy may be considered in elderly UC patients with CMV colitis and taking immunosuppressive medications even when subtotal colectomy is performed, because they could be more immunocompromised than young patients and develop CMV disease in other organs. CMV-associated ileal perforation is relatively uncommon and has been reported in patients with AIDS [5, 6]. It was also recently reported in immunosuppressed patients with malignant tumors [3, 7], lupus enteritis [8], rheumatoid arthritis [9], and drug-induced hypersensitivity syndrome [10]. In addition, Cha et al. [4] reported an elderly immunocompetent patient with ileal perforation in a literature review. Our patient was elderly with severe, steroidrefractory UC and CMV colitis. We performed subtotal colectomy with end ileostomy and mucous fistula formation in the sigmoid colon for a colonic perforation. However, the patient developed ileal perforation after surgery. Recently, Uchino et al. [23] have reported multiple perforations due to diffuse gastroduodenitis and enteritis associated with UC and concomitant CMV reactivation after total proctocolectomy. Though the case was diagnosed based on serological and endoscopic findings with negative histopathological findings in biopsy examination, the serological study could be affected by CMV infection in the colon because CMV reactivation was suspected serologically before total proctocolectomy. On the other hand, we diagnosed it on the basis of histopathological findings in the surgical specimen. No cases of ileal perforation caused by CMV infection in UC which was diagnosed pathologically have been previously reported, including nonoperative and postoperative cases. It is important to consider ileitis caused by CMV reactivation in UC patients with immunosuppressive therapies and we could show a case with pathological proof. In summary, we demonstrated a case of small intestinal perforation caused by CMV reactivation after subtotal
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colectomy for UC. This is the first report of ileal perforation due to CMV infection confirmed pathologically in a patient with UC. Our report could help many physicians to be aware of the possibility of this rare complication in UC and the risk associated with high-dose steroid therapy for elderly UC patients. Conflict of interest of interest.
The authors declare that they have no conflict
References 1. Nguyen M, Bradford K, Zhang X, Shih DQ. Cytomegalovirus reactivation in ulcerative colitis patients. Ulcers. 2011;. doi: 10.1155. 2. Domenech E, Vega R, Ojanguren I, Hernandez A, GarciaPlanella E, Bernal I, et al. Cytomegalovirus infection in ulcerative colitis: a prospective, comparative study on prevalence and diagnostic strategy. Inflamm Bowel Dis. 2008;14:1373–9. 3. Nishii T, Rino Y, Ando K, Matsuzu K, Wada H, Chiba A, et al. Successful treatment of multiple small-bowel perforations caused by cytomegalovirus in a patient with malignant lymphoma: report of a case. Surg Today. 2006;36:930–3. 4. Cha JM, Lee JI, Choe JW, Joo KR, Jung SW, Shin HP, et al. Cytomegalovirus enteritis causing ileal perforation in an elderly immunocompetent individual. Yonsei Med J. 2010;51:279–83. 5. Meza AD, Bin-Sagheer S, Zuckerman MJ, Morales CA, Verghese A. Ileal perforation due to cytomegalovirus infection. J Natl Med Assoc. 1994;86:145–8. 6. Kram HB, Shoemaker WC. Intestinal perforation due to cytomegalovirus infection in patients with AIDS. Dis Colon Rectum. 1990;33:1037–40. 7. Kawate S, Ohwada S, Sano T, Kawashima Y, Kishikawa I, Tomizawa N, et al. Ileal perforation caused by cytomegalovirus infection in a patient with recurrent gastric cancer: report of a case. Surg Today. 2002;32:1088–90. 8. Bang S, Park YB, Kang BS, Park MC, Hwang MH, Kim HK, et al. CMV enteritis causing ileal perforation in underlying lupus enteritis. Clin Rheumatol. 2004;23:69–72. 9. Ishiguro T, Takayanagi N, Kawabata Y, Sugita Y. Intestinal perforation due to concomitant cytomegalovirus infection during treatment for Pneumocystis jirovecii pneumonia in a patient with rheumatoid arthritis. Intern Med. 2011;50:1835–7. 10. Sano S, Ueno H, Yamagami K, Yakushiji Y, Isaka Y, Kawasaki I, et al. Isolated ileal perforation due to cytomegalovirus reactivation during management of terbinafine hypersensitivity. World J Gastroenterol. 2010;16:3339–42. 11. Goodgame RW. Gastrointestinal cytomegalovirus disease. Ann Intern Med. 1993;119:924–35. 12. Taylor GH. Cytomegalovirus. Am Fam Physician. 2003;67: 519–24. 13. Rafailidis PI, Mourtzoukou EG, Varbobitis IC, Falagas ME. Severe cytomegalovirus infection in apparently immunocompetent patients: a systematic review. Virol J. 2008;5:47. 14. Spencer SP, Power N. The acute abdomen in the immune compromised host. Cancer Imaging. 2008;8:93–101. 15. Kaufman HS, Kahn AC, Iacobuzio-Donahue C, Talamini MA, Lillemoe KD, Hamilton SR. Cytomegaloviral enterocolitis: clinical associations and outcome. Dis Colon Rectum. 1999;42:24–30. 16. Tejedor Cerdena MA, Velasco Guardado A, Fernandez Prodomingo A, Concepcion Pinero Perez MC, Calceron R, Prieto Bermejo AB, et al. Cytomegalovirus ileitis in an immunocompetent patient. Rev Esp Enferm Dig. 2011;103:154–6.
Clin J Gastroenterol (2013) 6:111–115 17. Ryu KH, Yi SY. Cytomegalovirus ileitis in an immunocompetent elderly adult. World J Gastroenterol. 2006;12:5084–6. 18. Galiatsatos P, Shrier I, Lamoureux E, Szilagyi A. Meta-analysis of outcome of cytomegalovirus colitis in immunocompetent hosts. Dig Dis Sci. 2005;50:609–16. 19. Maher MM, Nassar MI. Acute cytomegalovirus infection is a risk factor in refractory and complicated inflammatory bowel disease. Dig Dis Sci. 2009;54:2456–62. 20. Ho GT, Mowat C, Goddard CJ, Fennell JM, Shah NB, Prescott RJ, et al. Predicting the outcome of severe ulcerative colitis: development of a novel risk score to aid early selection of patients for second-line medical therapy or surgery. Aliment Pharmacol Ther. 2004;19:1079–87.
115 21. Matsuoka K, Iwao Y, Mori T, Sakuraba A, Yajima T, Hisamatsu T, et al. Cytomegalovirus is frequently reactivated and disappears without antiviral agents in ulcerative colitis patients. Am J Gastroenterol. 2007;102:331–7. 22. Alcala MJ, Casellas F, Pallares J, de Torres I, Malagelada JR. Infection by cytomegalovirus in patients with ulcerative colitis requiring colonic resection. Med Clin (Barc). 2000;114:201–4. 23. Uchino M, Ikeuchi H, Bando T, Matsuoka H, Hirata A, Takahashi Y, et al. Diffuse gastroduodenitis and enteritis associated with ulcerative colitis and concomitant cytomegalovirus reactivation after total colectomy: report of a case. Surg Today. 2012 (Epub ahead of print).
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CASE REPORT
Small intestinal perforation caused by cytomegalovirus reactivation after subtotal colectomy for ulcerative colitis: report of a case Hiroyuki Fujikawa • Toshimitsu Araki • Tadanobu Shimura • Yoshiki Okita Koji Tanaka • Mikihiro Inoue • Mikio Kawamura • Yasuhiro Inoue • Yasuhiko Mohri • Keiichi Uchida • Masato Kusunoki
•
Received: 22 November 2012 / Accepted: 15 January 2013 / Published online: 15 February 2013 Ó Springer Japan 2013
Abstract A 79-year-old woman with bloody diarrhea was diagnosed with ulcerative colitis. She developed intestinal perforation after high-dose steroid therapy. An emergency laparotomy revealed a perforation in the ascending colon, and a subtotal colectomy was performed with an ileostomy and a mucous fistula in the sigmoid colon. Histological findings of the resected colon showed the presence of cytomegalovirus in the endothelial cells of vessels around the ulcer floor. Twelve days after the laparotomy, she developed an ileal perforation with a bloody discharge from the ileostomy and underwent an emergency laparotomy. Multiple intestinal perforations were found in the ileum, and the perforated ileum was resected. Cytomegalovirus infection was controlled with ganciclovir postoperatively. Histological findings of the resected ileum showed the presence of cytomegalovirus in the endothelial cells of vessels around the ulcer floor. This is the first report of ileal perforation due to cytomegalovirus infection confirmed pathologically in a patient with ulcerative colitis.
Increased risk for reactivation of cytomegalovirus (CMV) disease in patients with ulcerative colitis (UC) compared to the general population is thought to be due to both iatrogenic and inherent factors [1]. One of the risk factors is that patients are immunocompromised with the use of immunosuppressive agents such as corticosteroids, cyclosporine, azathioprine, and infliximab [1, 2]. CMV colitis is frequently found in immunocompromised patients with severe UC and may require surgical treatment because of the development of large bowel perforation. Ileal perforation due to CMV infection confirmed pathologically in patients with UC has not been reported though there are reports of several diseases with immunocompromised status [3–10]. We herein report a case of ileal perforation associated with CMV reactivation confirmed pathologically after a subtotal colectomy for large bowel perforation with CMV colitis in a UC patient.
Keywords Cytomegalovirus Perforation Ileum Ulcerative colitis
Case report
H. Fujikawa (&) T. Araki T. Shimura Y. Okita K. Tanaka M. Inoue M. Kawamura Y. Inoue Y. Mohri K. Uchida M. Kusunoki Division of Reparative Medicine, Department of Gastrointestinal and Pediatric Surgery, Institute of Life Sciences, Mie University Graduate School of Medicine, 2-174, Edobashi, Tsu, Mie 514-8507, Japan e-mail: [email protected]
A 79-year-old woman newly diagnosed with UC 1 month earlier was admitted to a nearby hospital for evaluation of elevated fever and exacerbations of abdominal pain and diarrhea. Colonoscopy revealed an edematous, granular mucosa with small erosions on the day of admission and, a few days later, an extended ulcerative lesion. These findings were consistent with severely active UC, and prednisolone (PSL) at 50 mg/day was begun. The PSL dosage was gradually reduced to 25 mg/day because her symptoms appeared to improve. However, her symptoms became exacerbated again, and the PSL dosage was increased to 40 mg/day. Another colonoscopy revealed a punched-out
Introduction
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112
ulcer with bleeding (Fig. 1a). A few days later, a blood test for CMV antigenemia was positive, and she was treated with antiviral therapy and a decreased dosage of PSL. Her symptoms did not improve in spite of additional treatment with cytapheresis. She developed severe abdominal pain 54 days after admission, and abdominal computed tomography (CT) showed free air. She was transferred to our hospital for surgical treatment with a diagnosis of intestinal perforation. One site of bowel perforation was found at the cecum, and we performed a subtotal colectomy with end ileostomy and mucous fistula formation in the sigmoid colon. Grossly, the surgical specimen demonstrated lesions of wide mucous ulceration with several pseudopolypoid formations in the pan-colon and perforation in the cecum. The pathological findings showed areas of preserved mucosa with marked inflammatory changes, mainly cryptal distortion, with superficial lymphangiectasia and lymphoplasmacytic infiltration of the lamina propria. Also present were several eosinophils and neutrophils, which spread transmurally, mainly in the ulcerated lesions. Inclusion bodies were present in histological findings (Fig. 1b) and immunohistochemical staining for CMV showed a positive reaction in endothelial cells of vessels around the ulcer floor (Fig. 1c). The diagnosis was Fig. 1 Preoperative endoscopic findings of the colon and histological findings of the resected colon. a Colonoscopy revealed punched-out ulcerations with deep floors in the transverse colon. b Histology showed inclusion bodies (arrow). c Immunohistochemical staining was performed by antibodies against cytomegalovirus, and inclusion bodies were stained in the cytoplasm of endothelial cells (arrows)
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confirmed as a large bowel perforation due to CMV colitis with UC. After surgery, the patient’s condition improved with polymyxin B-immobilized fiber column (PMX) hemoperfusion and continuous hemodiafiltration, and without antiviral therapy. Twelve days after the laparotomy, she developed a bloody discharge from the ileostomy with low-grade fever, leukocytosis and mild elevation of serum C-reactive protein. Abdominal pain and tenderness were unclear because of the condition under mild sedation. Endoscopy revealed ulcerations with deep floors in the ileum 8 and 12 cm from the end of the ileostomy (Fig. 2a) and we investigated only up to the lumen with the ulcerations. CT showed free air around the stoma site, and we performed an emergency operation with the diagnosis of small bowel perforation. Operative findings showed two ileal perforations in the ileum that matched the sites of ulceration in the endoscopic findings. The ileum from the open end of stoma to the perforated lesion was resected (Fig. 2b), and an end-ileostomy was reconstructed. We did not find other pathological lesions in the serous surface of the small intestine and the ileal lumen near the resection stump. Immunohistological findings of the resected ileum showed CMV inclusion in the endothelial cells of vessels around the ulcer floor (Fig. 2c).
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Fig. 2 Preoperative endoscopic findings, gross appearance of the resected small bowel, and histological findings. a Endoscopy revealed ulcerations with punched-out lesions and bleeding. b The surgical specimen showed deep ulcerations with two perforative lesions (arrow). c Inclusion bodies were stained in the cytoplasm of endothelial cells by immunohistochemistry
The diagnosis was confirmed as multiple ileal perforations due to CMV ileitis. In addition, a blood test for CMV antigenemia after surgery was positive. After surgery, we administered ganciclovir for CMV reactivation and performed PMX hemoperfusion for endotoxin removal. She did not develop a bloody discharge from the ileostomy after surgery and we confirmed that a blood test for CMV antigenemia was negative on postoperative day 10. Although a postoperative wound infection and exacerbation of chronic heart failure due to dilated cardiomyopathy developed, her condition improved and she was transferred to another hospital for continued treatment. She was discharged 5 months after her primary surgery, remains asymptomatic, and is undergoing no specific treatment.
Discussion CMV is a member of the Herpesviridae family. It generally infects 40–100 % of healthy individuals [11], and primary CMV infection is acquired early in life. Although CMV infections are commonly asymptomatic, they can produce a mild mononucleosis-like syndrome [12]. CMV disease can occur in various organs, such as the lung, liver, gastrointestinal tract, retina, and brain [13]. The most common site in
the gastrointestinal tract is the colon; CMV infection can occur anywhere from the esophagus to the rectum [3]. Gastrointestinal involvement in CMV infection may comprise vasculitis in the affected segment, resulting in ischemia and infarction [14]. CMV infections are generally reactivated in patients who are immunocompromised due to factors such as acquired immunodeficiency syndrome (AIDS), organ transplants, malignant tumors, chemotherapy, and immunosuppressive medications [15]. CMV enterocolitis has been reported in both older immunocompetent hosts and immunocompromised hosts [4, 16, 17]. This shows an age-related dysfunction of the immune system, which may weaken with age; the perturbation of mucosal immunity can predispose these patients to development of various infectious and inflammatory diseases [16, 17]. A meta-analysis of the outcome of CMV colitis in immunocompetent hosts showed that most patients were older than 55 years and showed comorbidities (77.3 %) [18]. Severe, steroid-refractory UC especially occurs together with CMV colitis [2, 19], and such patients are usually treated with immunosuppressive medications. Systemic steroid therapy is the gold standard in management of acute moderate to severe flare-ups of UC [2], and steroidrefractory patients require rescue therapies such as immunosuppressive agents [20]. These treatments have been
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associated with an increased risk of CMV colitis in UC [2]. A prospective study reported that CMV reactivation was only observed in patients on systemic steroid therapy, not in patients with active UC before starting steroid therapy [21]. In addition, patients with severe and steroid-refractory UC are likely to undergo a colectomy, and CMV infection has been confirmed in 19 % of patients who have undergone colectomies [22]. Interestingly, Matsuoka et al. [21] reported that antiviral therapies should not be necessary for most UC patients with only CMV reactivation as long as the CMV antigen values are low, while the efficacy of ganciclovir in CMV infection has been widely recognized. In CMV colitis, the necessity for antiviral therapy after colectomy has been unclear except in cases of CMV disease in other organs because most of the colon with CMV infection was resected, and therefore the patient was not treated with antiviral therapy. However, antiviral therapy may be considered in elderly UC patients with CMV colitis and taking immunosuppressive medications even when subtotal colectomy is performed, because they could be more immunocompromised than young patients and develop CMV disease in other organs. CMV-associated ileal perforation is relatively uncommon and has been reported in patients with AIDS [5, 6]. It was also recently reported in immunosuppressed patients with malignant tumors [3, 7], lupus enteritis [8], rheumatoid arthritis [9], and drug-induced hypersensitivity syndrome [10]. In addition, Cha et al. [4] reported an elderly immunocompetent patient with ileal perforation in a literature review. Our patient was elderly with severe, steroidrefractory UC and CMV colitis. We performed subtotal colectomy with end ileostomy and mucous fistula formation in the sigmoid colon for a colonic perforation. However, the patient developed ileal perforation after surgery. Recently, Uchino et al. [23] have reported multiple perforations due to diffuse gastroduodenitis and enteritis associated with UC and concomitant CMV reactivation after total proctocolectomy. Though the case was diagnosed based on serological and endoscopic findings with negative histopathological findings in biopsy examination, the serological study could be affected by CMV infection in the colon because CMV reactivation was suspected serologically before total proctocolectomy. On the other hand, we diagnosed it on the basis of histopathological findings in the surgical specimen. No cases of ileal perforation caused by CMV infection in UC which was diagnosed pathologically have been previously reported, including nonoperative and postoperative cases. It is important to consider ileitis caused by CMV reactivation in UC patients with immunosuppressive therapies and we could show a case with pathological proof. In summary, we demonstrated a case of small intestinal perforation caused by CMV reactivation after subtotal
123
Clin J Gastroenterol (2013) 6:111–115
colectomy for UC. This is the first report of ileal perforation due to CMV infection confirmed pathologically in a patient with UC. Our report could help many physicians to be aware of the possibility of this rare complication in UC and the risk associated with high-dose steroid therapy for elderly UC patients. Conflict of interest of interest.
The authors declare that they have no conflict
References 1. Nguyen M, Bradford K, Zhang X, Shih DQ. Cytomegalovirus reactivation in ulcerative colitis patients. Ulcers. 2011;. doi: 10.1155. 2. Domenech E, Vega R, Ojanguren I, Hernandez A, GarciaPlanella E, Bernal I, et al. Cytomegalovirus infection in ulcerative colitis: a prospective, comparative study on prevalence and diagnostic strategy. Inflamm Bowel Dis. 2008;14:1373–9. 3. Nishii T, Rino Y, Ando K, Matsuzu K, Wada H, Chiba A, et al. Successful treatment of multiple small-bowel perforations caused by cytomegalovirus in a patient with malignant lymphoma: report of a case. Surg Today. 2006;36:930–3. 4. Cha JM, Lee JI, Choe JW, Joo KR, Jung SW, Shin HP, et al. Cytomegalovirus enteritis causing ileal perforation in an elderly immunocompetent individual. Yonsei Med J. 2010;51:279–83. 5. Meza AD, Bin-Sagheer S, Zuckerman MJ, Morales CA, Verghese A. Ileal perforation due to cytomegalovirus infection. J Natl Med Assoc. 1994;86:145–8. 6. Kram HB, Shoemaker WC. Intestinal perforation due to cytomegalovirus infection in patients with AIDS. Dis Colon Rectum. 1990;33:1037–40. 7. Kawate S, Ohwada S, Sano T, Kawashima Y, Kishikawa I, Tomizawa N, et al. Ileal perforation caused by cytomegalovirus infection in a patient with recurrent gastric cancer: report of a case. Surg Today. 2002;32:1088–90. 8. Bang S, Park YB, Kang BS, Park MC, Hwang MH, Kim HK, et al. CMV enteritis causing ileal perforation in underlying lupus enteritis. Clin Rheumatol. 2004;23:69–72. 9. Ishiguro T, Takayanagi N, Kawabata Y, Sugita Y. Intestinal perforation due to concomitant cytomegalovirus infection during treatment for Pneumocystis jirovecii pneumonia in a patient with rheumatoid arthritis. Intern Med. 2011;50:1835–7. 10. Sano S, Ueno H, Yamagami K, Yakushiji Y, Isaka Y, Kawasaki I, et al. Isolated ileal perforation due to cytomegalovirus reactivation during management of terbinafine hypersensitivity. World J Gastroenterol. 2010;16:3339–42. 11. Goodgame RW. Gastrointestinal cytomegalovirus disease. Ann Intern Med. 1993;119:924–35. 12. Taylor GH. Cytomegalovirus. Am Fam Physician. 2003;67: 519–24. 13. Rafailidis PI, Mourtzoukou EG, Varbobitis IC, Falagas ME. Severe cytomegalovirus infection in apparently immunocompetent patients: a systematic review. Virol J. 2008;5:47. 14. Spencer SP, Power N. The acute abdomen in the immune compromised host. Cancer Imaging. 2008;8:93–101. 15. Kaufman HS, Kahn AC, Iacobuzio-Donahue C, Talamini MA, Lillemoe KD, Hamilton SR. Cytomegaloviral enterocolitis: clinical associations and outcome. Dis Colon Rectum. 1999;42:24–30. 16. Tejedor Cerdena MA, Velasco Guardado A, Fernandez Prodomingo A, Concepcion Pinero Perez MC, Calceron R, Prieto Bermejo AB, et al. Cytomegalovirus ileitis in an immunocompetent patient. Rev Esp Enferm Dig. 2011;103:154–6.
Clin J Gastroenterol (2013) 6:111–115 17. Ryu KH, Yi SY. Cytomegalovirus ileitis in an immunocompetent elderly adult. World J Gastroenterol. 2006;12:5084–6. 18. Galiatsatos P, Shrier I, Lamoureux E, Szilagyi A. Meta-analysis of outcome of cytomegalovirus colitis in immunocompetent hosts. Dig Dis Sci. 2005;50:609–16. 19. Maher MM, Nassar MI. Acute cytomegalovirus infection is a risk factor in refractory and complicated inflammatory bowel disease. Dig Dis Sci. 2009;54:2456–62. 20. Ho GT, Mowat C, Goddard CJ, Fennell JM, Shah NB, Prescott RJ, et al. Predicting the outcome of severe ulcerative colitis: development of a novel risk score to aid early selection of patients for second-line medical therapy or surgery. Aliment Pharmacol Ther. 2004;19:1079–87.
115 21. Matsuoka K, Iwao Y, Mori T, Sakuraba A, Yajima T, Hisamatsu T, et al. Cytomegalovirus is frequently reactivated and disappears without antiviral agents in ulcerative colitis patients. Am J Gastroenterol. 2007;102:331–7. 22. Alcala MJ, Casellas F, Pallares J, de Torres I, Malagelada JR. Infection by cytomegalovirus in patients with ulcerative colitis requiring colonic resection. Med Clin (Barc). 2000;114:201–4. 23. Uchino M, Ikeuchi H, Bando T, Matsuoka H, Hirata A, Takahashi Y, et al. Diffuse gastroduodenitis and enteritis associated with ulcerative colitis and concomitant cytomegalovirus reactivation after total colectomy: report of a case. Surg Today. 2012 (Epub ahead of print).
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