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Endo K, Satoh T, Yoshino Y, Kondo S, Kawakami Y, Fukushi D, Takasu A, Kogure T, Hirota M, Satoh K. A case of relapsed pan-colonic ulcerative colitis accompanied with gastroduodenal lesions immediately after COVID-19. Clin J Gastroenterol 2025; 18:399-407. [PMID: 40024991 PMCID: PMC12095360 DOI: 10.1007/s12328-025-02107-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Accepted: 02/16/2025] [Indexed: 03/04/2025]
Abstract
Some patients with ulcerative colitis (UC) suffer from complicated UC-associated upper gastrointestinal lesions. However, the trigger of these lesions has not been clarified. Herein, we present a 28-year-old man with relapsed pan-colonic UC accompanied by gastroduodenal lesions immediately after contracting coronavirus disease 2019 (COVID-19). In this patient, UC relapsed approximately 7 days after the COVID-19 onset, despite being in remission for 3 years. The patient also developed symptoms such as epigastric pain and nausea on day 19 of COVID-19. The endoscopic and pathologic findings of the stomach and duodenum closely resembled colorectal lesions of UC; accordingly, we diagnosed the patient with UC-associated gastroduodenal lesions. Corticosteroids were significantly effective in the colorectal and upper gastrointestinal lesions, leading to remission. This report is the first to describe UC-associated upper GI lesions that developed right after COVID-19 infection. Therefore, COVID-19 can be a possible trigger of UC-associated upper gastrointestinal lesion. Further studies are needed to understand the relationship between the onset of UC or UC-associated upper GI lesions and COVID-19.
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Affiliation(s)
- Katsuya Endo
- Division of Gastroenterology, Tohoku Medical and Pharmaceutical University School of Medicine, 1-15-1 Fukumuro, Miyagino-ku, Sendai, Miyagi, 983-8536, Japan.
| | - Tomonori Satoh
- Division of Gastroenterology, Tohoku Medical and Pharmaceutical University School of Medicine, 1-15-1 Fukumuro, Miyagino-ku, Sendai, Miyagi, 983-8536, Japan
| | - Yuki Yoshino
- Division of Gastroenterology, Tohoku Medical and Pharmaceutical University School of Medicine, 1-15-1 Fukumuro, Miyagino-ku, Sendai, Miyagi, 983-8536, Japan
| | - Shiho Kondo
- Division of Gastroenterology, Tohoku Medical and Pharmaceutical University School of Medicine, 1-15-1 Fukumuro, Miyagino-ku, Sendai, Miyagi, 983-8536, Japan
| | - Yoko Kawakami
- Division of Gastroenterology, Tohoku Medical and Pharmaceutical University School of Medicine, 1-15-1 Fukumuro, Miyagino-ku, Sendai, Miyagi, 983-8536, Japan
| | - Daisuke Fukushi
- Division of Gastroenterology, Tohoku Medical and Pharmaceutical University School of Medicine, 1-15-1 Fukumuro, Miyagino-ku, Sendai, Miyagi, 983-8536, Japan
| | - Atsuko Takasu
- Division of Gastroenterology, Tohoku Medical and Pharmaceutical University School of Medicine, 1-15-1 Fukumuro, Miyagino-ku, Sendai, Miyagi, 983-8536, Japan
| | - Takayuki Kogure
- Division of Gastroenterology, Tohoku Medical and Pharmaceutical University School of Medicine, 1-15-1 Fukumuro, Miyagino-ku, Sendai, Miyagi, 983-8536, Japan
| | - Morihisa Hirota
- Division of Gastroenterology, Tohoku Medical and Pharmaceutical University School of Medicine, 1-15-1 Fukumuro, Miyagino-ku, Sendai, Miyagi, 983-8536, Japan
| | - Kennichi Satoh
- Division of Gastroenterology, Tohoku Medical and Pharmaceutical University School of Medicine, 1-15-1 Fukumuro, Miyagino-ku, Sendai, Miyagi, 983-8536, Japan
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Sathiaseelan M, Chiu KY, Lim A, Ravikumara M. Infliximab monotherapy for ulcerative colitis-related severe enteritis following colectomy in a paediatric patient. BMJ Case Rep 2024; 17:e259853. [PMID: 39515825 DOI: 10.1136/bcr-2024-259853] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2024] Open
Abstract
We report the rare entity of ulcerative colitis-related severe enteritis (UCRSE) following colectomy in a child. This entity has been described primarily in adults and is characterised by diffuse enteritis with histology identical to ulcerative colitis (UC). The mainstay treatment is steroids and in recent years anti-tumour necrosis factor agents.A boy in early adolescence required urgent colectomy for medically refractory severe acute colitis. Colectomy specimen histology confirmed UC. Postoperatively, he developed fevers, severe abdominal pain and excessive stoma output (5 L/day). Endoscopy revealed severe extensive enteritis, histologically resembling UC. Infliximab (IFX) was commenced with significant improvement. He remains asymptomatic 28 months post-colectomy on maintenance IFX monotherapy. To our knowledge, this is the youngest patient with this complication.This case illustrates the need to consider UCRSE in a child with otherwise unexplained fever, severe abdominal pain and high stoma output post colectomy. IFX monotherapy is a successful treatment option.
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Affiliation(s)
- Mohana Sathiaseelan
- Dept of Gastroenterology and Hepatology, Perth Children's Hospital, Nedlands, Western Australia, Australia
| | - Kei Yu Chiu
- Dept of Gastroenterology and Hepatology, Perth Children's Hospital, Nedlands, Western Australia, Australia
| | - Alicia Lim
- Dept of Gastroenterology and Hepatology, Perth Children's Hospital, Nedlands, Western Australia, Australia
| | - Madhur Ravikumara
- Dept of Gastroenterology and Hepatology, Perth Children's Hospital, Nedlands, Western Australia, Australia
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Masaki S, Honjo H, Kurimoto M, Okai N, Otsuka Y, Masuta Y, Kamata K, Minaga K, Kudo M, Watanabe T. Concurrent occurrence of ulcerative duodenitis and ulcerative colitis displaying unique responses to golimumab and ustekinumab. Clin J Gastroenterol 2024; 17:854-860. [PMID: 39023824 DOI: 10.1007/s12328-024-02012-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Accepted: 06/25/2024] [Indexed: 07/20/2024]
Abstract
Recent studies have reported the occurrence of upper gastrointestinal (UGI) inflammation in patients with ulcerative colitis (UC). However, whether UC-associated UGI and colorectal lesions share pathogenic cytokine profiles and responses to biologics remains unknown. Herein, we report a case of concurrent UC and ulcerative duodenitis (UD) that displayed unique responses to biologic treatment. Although treatment with prednisolone (PSL) failed to induce remission in both disorders, golimumab (GLM) and ustekinumab (UST) were effective against UD and UC, respectively, and remission of both disorders was achieved using UST. Immunofluorescence analyses revealed that numbers of immune cells expressing TNF-α were comparable in both duodenal and rectal mucosa before the treatment. GLM or UST treatment markedly decreased numbers of TNF-α-expressing duodenal immune cells, suggesting the presence of correlation between TNF-α expression and disease activity of UD. In contrast, TNF-α expression was not parallel to disease activity of UC because GLM or PSL failed to induce remission despite a marked reduction in TNF-α expression. Responsiveness to GLM or UST together with immunofluorescence studies suggests that TNF-α and IL-12/23p40 are pathogenic cytokines causing UD and UC, respectively, in the present case.
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Affiliation(s)
- Sho Masaki
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan
| | - Hajime Honjo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan
| | - Masayuki Kurimoto
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan
| | - Natsuki Okai
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan
| | - Yasuo Otsuka
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan
| | - Yasuhiro Masuta
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan
| | - Ken Kamata
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan
| | - Kosuke Minaga
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan
| | - Tomohiro Watanabe
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan.
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Hayashi T, Terashima T, Nishitani M, Orita N, Miyazawa M, Seki A, Nakagawa H, Nio K, Iida N, Yamada S, Takatori H, Shimakami T, Yamashita T. Gastroduodenitis Associated with Active Ulcerative Colitis Treated with Infliximab: Different Clinical Course in the Colon and Gastroduodenal Lesions. Intern Med 2024; 63:929-935. [PMID: 37495533 PMCID: PMC11045365 DOI: 10.2169/internalmedicine.2047-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Accepted: 06/12/2023] [Indexed: 07/28/2023] Open
Abstract
A 29-year-old man with severe ulcerative colitis and gastroduodenitis was initially treated with oral mesalamine and high-dose intravenous steroid therapy; however, his epigastralgia and vomiting did not improve. After initiating infliximab, the patient experienced prompt improvement in symptoms and inflammation. Although steroids were effective for the colon, they proved ineffective for gastroduodenal lesions, highlighting the necessity for molecular-targeted agents, such as infliximab, in these cases. The timing for administering such agents should be carefully considered.
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Affiliation(s)
- Tomoyuki Hayashi
- Department of Gastroenterology, Kanazawa University Hospital, Japan
| | | | - Masaki Nishitani
- Department of Gastroenterology, Kanazawa University Hospital, Japan
| | - Noriaki Orita
- Department of Gastroenterology, Kanazawa University Hospital, Japan
| | - Masaki Miyazawa
- Department of Gastroenterology, Kanazawa University Hospital, Japan
| | - Akihiro Seki
- Department of Gastroenterology, Kanazawa University Hospital, Japan
| | | | - Kouki Nio
- Department of Gastroenterology, Kanazawa University Hospital, Japan
| | - Noriho Iida
- Department of Gastroenterology, Kanazawa University Hospital, Japan
| | - Shinya Yamada
- Endoscopy Center, Kanazawa University Hospital, Japan
| | | | | | - Taro Yamashita
- Department of Gastroenterology, Kanazawa University Hospital, Japan
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Guo C, He S, Wang H. Case report: Successful treatment of ulcerative colitis-related post-colectomy enteritis refractory to multiple therapies with ustekinumab. Front Immunol 2024; 15:1297508. [PMID: 38433841 PMCID: PMC10904456 DOI: 10.3389/fimmu.2024.1297508] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Accepted: 01/31/2024] [Indexed: 03/05/2024] Open
Abstract
Ulcerative colitis-related severe post-colectomy enteritis is a rare condition. A few cases have undergone successful treatment with corticosteroids, Cyclosporine, Azathioprine, and Infliximab. We aim to evaluate the treatment outcome of ustekinumab in this rare case. Here we describe a 56-year-old woman with post-colectomy enteritis refractory to multiple therapies. Finally, the patient was administered with ustekinumab treatment. Under monitoring, the feces volume of the patient decreased from 5000-7000 mL per day to 1700-2000 mL. Over a one-year follow-up period, the patient gradually gained body weight, with the stoma drainage of formed brown stool. And the villi of the small intestinal mucosa restore growth. To our knowledge, this is the first report that indicates ustekinumab could be a treatment selection for ulcerative colitis-related severe post-colectomy enteritis.
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Affiliation(s)
| | | | - Huahong Wang
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
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A case of ulcerative colitis-related postoperative enteritis treated with granulocyte and monocyte apheresis. Clin J Gastroenterol 2023; 16:43-47. [PMID: 36214972 DOI: 10.1007/s12328-022-01716-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Accepted: 09/28/2022] [Indexed: 11/06/2022]
Abstract
A 46-year-old man, receiving continuous steroid therapy for refractory ulcerative colitis with an insufficient response to anti-tumor necrosis factor-α therapy, presented with left buttock pain. He was diagnosed with steroidal left femoral head necrosis, and total proctocolectomy with permanent ileostomy was performed. At 6 months postoperatively, the patient developed general fatigue, abdominal pain, and severe ileostomy diarrhea. Computed tomography revealed continuous intestinal edema from the descending duodenal leg to the upper jejunum. Gastrointestinal endoscopy revealed deep ulcers, coarse mucosa, and duodenal erosion. Based on clinical progress, findings, and pathology, the patient was diagnosed with ulcerative colitis-related postoperative enteritis. Although 5-aminosalicylic acid treatment was initiated, his symptoms persisted, bloody diarrhea from colostomy was observed. Subsequently, granulocyte and monocyte apheresis treatment was added. Symptoms and endoscopic findings improved with granulocyte and monocyte apheresis. Azathioprine was introduced as maintenance therapy, and no sign of recurrence was observed. Although ulcerative colitis-related postoperative enteritis has no definitive treatment, granulocyte and monocyte apheresis may be considered for initial treatment.
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Hawa K, Maltz R, Donegan A, Prasad V, Dotson JL, Boyle B, Michel HK. Postcolectomy Enteritis in a Pediatric Patient With Ulcerative Colitis. JPGN REPORTS 2022; 3:e255. [PMID: 37168479 PMCID: PMC10158275 DOI: 10.1097/pg9.0000000000000255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Accepted: 07/25/2022] [Indexed: 05/13/2023]
Abstract
Postcolectomy enteritis is characterized by diffuse small bowel inflammatory changes following colectomy for medically refractory ulcerative colitis. Symptoms may include abdominal pain, massive intestinal bleeding, intestinal perforation, and high stoma output. While the exact pathogenesis is unknown, immune dysregulation with increased cytokine and inflammatory cell response is suspected to lead to the inflammatory response. Therefore, immunosuppressive medications are the mainstay for treatment. All cases to date have been described in adult patients. We present a case of postcolectomy enteritis in a pediatric patient who improved without significant intervention.
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Affiliation(s)
- Kathryn Hawa
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Nationwide Children’s Hospital, Columbus, OH
| | - Ross Maltz
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Nationwide Children’s Hospital, Columbus, OH
- Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH
| | - Amy Donegan
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Nationwide Children’s Hospital, Columbus, OH
| | - Vinay Prasad
- Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH
- Department of Pathology, Nationwide Children’s Hospital, Columbus, OH
| | - Jennifer L. Dotson
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Nationwide Children’s Hospital, Columbus, OH
- Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH
- Center for Child Health Equity and Outcomes Research, The Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, OH
| | - Brendan Boyle
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Nationwide Children’s Hospital, Columbus, OH
- Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH
| | - Hilary K. Michel
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Nationwide Children’s Hospital, Columbus, OH
- Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH
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Horio Y, Uchino M, Hori K, Kusunoki K, Minagawa T, Kuwahara R, Kataoka K, Beppu N, Ikeda M, Ikeuchi H. Clinical Features and Therapeutic Outcomes of Post-colectomy Enteritis with Ulcerative Colitis. JOURNAL OF THE ANUS RECTUM AND COLON 2021; 5:405-413. [PMID: 34746505 PMCID: PMC8553349 DOI: 10.23922/jarc.2021-031] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Accepted: 07/06/2021] [Indexed: 12/23/2022]
Abstract
Objectives Few reports are available on post-colectomy enteritis (PCE) with ulcerative colitis (UC), which can be severe and sometimes fatal. The clinical characteristics are unclear, and treatment and diagnosis protocols have not been established. We aimed to investigate the incidence, clinical characteristics, diagnostic criteria, and therapeutic outcomes of PCE in this study. Methods Patients with UC who underwent colectomy between April 2010 and December 2019 were included in this study. We retrospectively analyzed patients who developed PCE and excluded patients with other forms of enteritis. Results We performed 829 colectomies because of a preoperative diagnosis of UC. Eleven and four patients were diagnosed with Crohn's disease and indeterminate colitis after surgery, respectively; 22 patients developed enteritis in the perioperative period. We excluded six patients with backwash ileitis, five with prepouch ileitis, three with infectious enteritis, and one with ischemic enteritis. In total, 7/814 (0.8%) patients developed PCE. All patients with PCE had pancolitis. PCE was observed a median of 33 (12-248) days after surgery. Endoscopy showed friable and granular mucosa. The extent of disease included various types such as pan-enteritis with diffuse type, pan-enteritis and mild inflammation in the middle ileum, and only ileitis. Gastroduodenitis-associated UC developed in 6/7 cases. All patients improved with tumor necrosis factor alpha (TNFα) antagonists even if TNFα antagonists had not been effective for colitis. Conclusions PCE was rare. The mucosal endoscopic findings were similar to those of UC, and the extent of disease varied. TNFα antagonist administration for PCE was effective.
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Affiliation(s)
- Yuki Horio
- Department of Gastroenterological Surgery, Hyogo College of Medicine, Hyogo, Japan
| | - Motoi Uchino
- Department of Gastroenterological Surgery, Hyogo College of Medicine, Hyogo, Japan
| | - Kazutoshi Hori
- Department of Intestinal Inflammation Research, Hyogo College of Medicine, Hyogo, Japan
| | - Kurando Kusunoki
- Department of Gastroenterological Surgery, Hyogo College of Medicine, Hyogo, Japan
| | - Tomohiro Minagawa
- Department of Gastroenterological Surgery, Hyogo College of Medicine, Hyogo, Japan
| | - Ryuichi Kuwahara
- Department of Gastroenterological Surgery, Hyogo College of Medicine, Hyogo, Japan
| | - Kozo Kataoka
- Department of Gastroenterological Surgery, Hyogo College of Medicine, Hyogo, Japan
| | - Naohito Beppu
- Department of Gastroenterological Surgery, Hyogo College of Medicine, Hyogo, Japan
| | - Masataka Ikeda
- Department of Gastroenterological Surgery, Hyogo College of Medicine, Hyogo, Japan
| | - Hiroki Ikeuchi
- Department of Gastroenterological Surgery, Hyogo College of Medicine, Hyogo, Japan
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Ulcerative colitis-related postoperative enteritis treated with anti-tumor necrosis factor therapy: two case reports and a literature review. Clin J Gastroenterol 2021; 14:1396-1403. [PMID: 34302278 DOI: 10.1007/s12328-021-01485-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Accepted: 07/18/2021] [Indexed: 10/20/2022]
Abstract
Several case reports have described severe postoperative enteritis shortly after total colectomy for ulcerative colitis. The very low incidence of this condition makes diagnosis and treatment difficult, and the appropriate treatment strategy is unclear. We report two cases of enteritis after surgery for ulcerative colitis, which were treated with anti-tumor necrosis factor-α therapy. Case 1 involved a 22-year-old man with symptoms, such as nausea 40 days after total colectomy. Gastrointestinal endoscopy revealed patchy obliteration of the vascular pattern, erosions in the duodenum, and superficial ulcers in the small intestine. His symptoms and endoscopic findings immediately improved upon administration of infliximab; clinical remission lasted 5 years with continuous administration. Case 2 involved a 64-year-old man, who had a large amount of watery diarrhea from ileostomy that increased 5 days after total colectomy; gastrointestinal endoscopy revealed extensive ulcers in the small intestine. Symptoms and endoscopic findings improved with prednisolone, but relapsed with tapering of the corticosteroid. Administration of adalimumab resulted in marked improvement of enteritis. However, the small intestine developed a pinhole stricture, and partial resection of the small intestine was performed. Our experience with two cases indicates that anti-tumor necrosis factor-α therapy may play an important role in ulcerative colitis-related postoperative enteritis.
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Rabbenou W, Chang S. Medical treatment of pouchitis: a guide for the clinician. Therap Adv Gastroenterol 2021; 14:17562848211023376. [PMID: 34249146 PMCID: PMC8239975 DOI: 10.1177/17562848211023376] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Accepted: 05/18/2021] [Indexed: 02/04/2023] Open
Abstract
Pouchitis is the most common complication in patients who have undergone restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA). Up to 81% of IPAA patients experience pouchitis, with 40% of patients presenting within the first year of surgery. Common risk factors include genetic mutations, extensive colitis, rheumatologic disorders, and primary sclerosing cholangitis. Currently, there are no medications with approved indications for pouchitis. As such, the conventional treatment of pouchitis is entirely off-label. This paper is intended to be a practical and up-to-date review of available therapies used for the management of pouchitis. The mainstay of treatment for acute pouchitis remains antibiotics, but newer therapeutics have also shown promise in the treatment of chronic pouchitis. Common lifestyle considerations that may play a role in pouchitis are also reviewed. PLAIN LANGUAGE SUMMARY Medical treatment of pouchitis: a guide for the clinician The ileal pouch-anal anastomosis ("pouch") is the most common way patients who require surgery to remove their colon are able to avoid a permanent ileostomy ("ostomy"). This pouch, created from the small intestines, serves as a reservoir to hold stool. The most common complication after pouch surgery is pouchitis. Pouchitis symptoms include more frequent bowel movements, urgency to defecate, blood in the stool, incontinence, and abdominal pain. This paper is intended to be a practical review of available therapies including medications and lifestyle changes that can be considered for the management of acute pouchitis, chronic pouchitis, and cuffitis.
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Affiliation(s)
- Wendy Rabbenou
- Division of Gastroenterology and Hepatology, New York University Langone Medical Center, New York, NY, USA
| | - Shannon Chang
- Division of Gastroenterology and Hepatology, New York University Langone Medical Center, 305 E 33rd Street, New York, NY 10016, USA
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Sun Y, Zhang Z, Zheng CQ, Sang LX. Mucosal lesions of the upper gastrointestinal tract in patients with ulcerative colitis: A review. World J Gastroenterol 2021; 27:2963-2978. [PMID: 34168401 PMCID: PMC8192286 DOI: 10.3748/wjg.v27.i22.2963] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 03/10/2021] [Accepted: 04/21/2021] [Indexed: 02/06/2023] Open
Abstract
Ulcerative colitis (UC) is a chronic, nonspecific, relapsing inflammatory bowel disease. The colorectum is considered the chief target organ of UC, whereas upper gastrointestinal (UGI) tract manifestations are infrequent. Recently, emerging evidence has suggested that UC presents complications in esophageal, stomachic, and duodenal mucosal injuries. However, UC-related UGI tract manifestations are varied and frequently silenced or concealed. Moreover, the endoscopic and microscopic characteristics of UGI tract complicated with UC are nonspecific. Therefore, UGI involvement may be ignored by many clinicians. In addition, no standard criteria have been established for patients with UC who should undergo fibrogastroduodenoscopy. Furthermore, specific treatment recommendations may be needed for patients with UC-associated UGI lesions. Herein, we review the esophageal, gastric, and duodenal mucosal lesions of the UC-associated UGI tract, as well as the potential pathogenesis and therapy.
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Affiliation(s)
- Yan Sun
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110022, Liaoning Province, China
| | - Zhe Zhang
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110022, Liaoning Province, China
| | - Chang-Qing Zheng
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110022, Liaoning Province, China
| | - Li-Xuan Sang
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110022, Liaoning Province, China
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Outtier A, Ferrante M. Chronic Antibiotic-Refractory Pouchitis: Management Challenges. Clin Exp Gastroenterol 2021; 14:277-290. [PMID: 34163205 PMCID: PMC8213947 DOI: 10.2147/ceg.s219556] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Accepted: 05/06/2021] [Indexed: 12/12/2022] Open
Abstract
Background Pouchitis is the most common long-term complication in patients with ulcerative colitis who underwent restorative proctocolectomy with ileal pouch-anal anastomosis. The incidence of acute pouchitis is 20% after 1 year and up to 40% after 5 years. Chronic antibiotic-refractory pouchitis develops in approximately 10% of patients. Aim To present a narrative review of published literature regarding the management of chronic antibiotic-refractory pouchitis. Methods Current relevant literature was summarized and critically evaluated. Results Clear definitions should be used to classify pouchitis into acute versus chronic, and responsive versus dependent versus refractory to antibiotics. Before treatment is started for chronic antibiotic-refractory pouchitis, secondary causes should be ruled out. There is a need for validated scoring systems to measure the severity of the disease. Because chronic antibiotic-refractory pouchitis is a rare condition, only small studies with often a poor study design have been performed. Treatments with antibiotics, aminosalicylates, steroids, immunomodulators and biologics have shown to be effective and safe for chronic antibiotic-refractory pouchitis. Also, treatments with AST-120, hyperbaric oxygen therapy, tacrolimus enemas, and granulocyte and monocyte apheresis suggested some efficacy. Conclusion The available data are weak but suggest that therapeutic options for chronic antibiotic-refractory pouchitis are similar to the treatment strategies for inflammatory bowel diseases. However, randomized controlled trials are warranted to further identify the best treatment options in this patient population.
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Affiliation(s)
- An Outtier
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium
| | - Marc Ferrante
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium
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Kohyama A, Watanabe K, Sugita A, Futami K, Ikeuchi H, Takahashi KI, Suzuki Y, Fukushima K. Ulcerative colitis-related severe enteritis: an infrequent but serious complication after colectomy. J Gastroenterol 2021; 56:240-249. [PMID: 33155079 DOI: 10.1007/s00535-020-01742-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2020] [Accepted: 10/19/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIM After colectomy for ulcerative colitis (UC), very severe and sometimes lethal enteritis can develop. However, the clinical features remain uncertain because of the low incidence, diversity of symptoms, and undefined diagnostic criteria. The aim of this study was to define postoperative ulcerative colitis-related severe enteritis (UCRSE) and to investigate its clinical features. METHODS A retrospective multicenter study was performed as a survey of major medical facilities utilizing surgical supplies for inflammatory bowel disease in Japan from 2001 to 2014. UCRSE was defined as a case with massive intestinal bleeding, intestinal perforation, high-output stoma, and/or a requirement for medications, such as steroids and biologics. Patients with gastroduodenal lesions or pouchitis alone were excluded. The incidence, symptoms, involvement of bacteria, cytomegalovirus reactivation, treatment, and prognosis were examined for patients with UCRSE after colectomy. RESULTS Forty-two (0.8%) out of 5284 cases met the criteria for UCRSE. Major symptoms were massive intestinal bleeding (76.2%), which required a median of 3850 (560-18900) mL blood transfusion; high-output stoma (38.1%) with excretion of fluid of 5000 (2000-7800) mL/day; and intestinal perforation (7.1%). Hypovolemic shock (35.7%) and/or disseminated intravascular coagulation (31.0%) developed as serious complications. Tests for cytomegalovirus reactivation were positive in 26.2% of cases. The presence of pathogenic bacteria was confirmed in only 5 cases. Corticosteroids or infliximabs were effective in half of the patients. Thirteen cases (31.0%) were treated surgically and 22 cases (56.4%) required maintenance therapy. The mortality rate was 11.9%. CONCLUSION UCRSE is a rare but serious complication after colectomy and is sometimes life-threatening.
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Affiliation(s)
- Atsushi Kohyama
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.
| | - Kazuhiro Watanabe
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
| | - Akira Sugita
- Department of Inflammatory Bowel Disease, Yokohama Municipal Citizen's Hospital, Yokohama, Japan
| | - Kitaro Futami
- Department of Surgery, Fukuoka University, Chikushi Hospital, Fukuoka, Japan
| | - Hiroki Ikeuchi
- Department of Inflammatory Bowel Disease, Hyogo College of Medicine, Nishinomiya, Japan
| | | | - Yasuo Suzuki
- Inflammatory Bowel Disease Center, Toho University Sakura Medical Center, Sakura, Japan
| | - Kouhei Fukushima
- Division of Surgical and Molecular Pathophysiology, Tohoku University Graduate School of Medicine, Sendai, Japan
- Laboratory of Gastrointestinal Tract Reconstruction, Tohoku University Graduate School of Biomedical Engineering, Sendai, Japan
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Abstract
Although the features of lower gastrointestinal tract inflammation associated with ulcerative colitis and Crohn disease are generally familiar to pathologists, there is less awareness of and familiarity with the manifestations of inflammatory bowel disease in the esophagus, stomach, and duodenum. Nonetheless, their diagnosis has therapeutic and possibly prognostic implications, potentially foretelling severe complications. The recognition that ulcerative colitis can affect gastrointestinal organs proximal to the large intestine and terminal ileum represents a revision of concepts ingrained among generations of physicians. This article reviews the pathologic features and clinical significance of esophagitis, gastritis, and duodenitis associated with inflammatory bowel disease.
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Affiliation(s)
- Noam Harpaz
- Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, Annenberg Building Room 15-38, 1468 Madison Avenue, New York, NY 10029, USA; Department of Medicine, Icahn School of Medicine at Mount Sinai, Annenberg Building Room 15-38, 1468 Madison Avenue, New York, NY 10029, USA.
| | - Alexandros D Polydorides
- Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, Annenberg Building Room 15-38, 1468 Madison Avenue, New York, NY 10029, USA; Department of Medicine, Icahn School of Medicine at Mount Sinai, Annenberg Building Room 15-38, 1468 Madison Avenue, New York, NY 10029, USA
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15
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Kitajima T, Okita Y, Kawamura M, Kondo S, Toiyama Y, Uchida K, Kusunoki M. The relationship between preoperative T helper cytokines in the ileal mucosa and the pathogenesis of pouchitis. BMC Gastroenterol 2020; 20:277. [PMID: 32811425 PMCID: PMC7437011 DOI: 10.1186/s12876-020-01421-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Accepted: 08/11/2020] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Although the etiology of pouchitis remains unknown, inflammatory cytokines are significantly associated with the pathogenesis of pouchitis. The cytokine responses that characterize inflammatory bowel diseases (IBD) are key pathogenic components of the disease. Although cytokine profiles in the colonic mucosa have been investigated in experimental colitis models or IBD patients, cytokine profiles in the ileal mucosa at colectomy have been rarely assessed. AIM To assess the relationship between pouchitis and T helper (Th) cytokines in the ileal mucosa collected at the time of colectomy and pouch construction. METHODS This retrospective study involved 68 consecutive patients from January 2004 to May 2011 who underwent ileal pouch-anal anastomosis for ulcerative colitis. Samples were obtained from the terminal ileum of resected specimens at time of total colectomy or subtotal colectomy. mRNA expression levels of Th cytokines (IFN-γ, IL-23A, IL-5, IL-13 and IL-17A) were determined. RESULTS Forty of 68 patients (58.8%) developed pouchitis. There was no association between IL-23A expression levels and incidence of pouchitis (p = 0.301). Patients with elevated IFN-γ had a significantly higher incidence of pouchitis compared with low IFN-γ patients (p = 0.043). Univariate analysis demonstrated a total dose of prednisolone > 7000 mg administered before colectomy (p = 0.04) and high IFN-γ expression (p = 0.02) were significant risk factors for pouchitis onset. In multivariate analysis, elevated IFN-γ messenger(m)RNA levels were significantly associated with pouchitis onset (p = 0.03). CONCLUSION IFN-γ expression in the normal ileal mucosa at the time of colectomy may be an important factor in the pathophysiology of pouchitis.
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Affiliation(s)
- Takahito Kitajima
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.
| | - Yoshiki Okita
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan
| | - Mikio Kawamura
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan
| | - Satoru Kondo
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan
| | - Yuji Toiyama
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan
| | - Keiichi Uchida
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan
| | - Masato Kusunoki
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan
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16
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Qin Z, Wang PY, Wan JJ, Zhang Y, Wei J, Sun Y, Liu X. MicroRNA124-IL6R Mediates the Effect of Nicotine in Inflammatory Bowel Disease by Shifting Th1/Th2 Balance Toward Th1. Front Immunol 2020; 11:235. [PMID: 32153570 PMCID: PMC7050625 DOI: 10.3389/fimmu.2020.00235] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2019] [Accepted: 01/28/2020] [Indexed: 12/20/2022] Open
Abstract
Epidemiological investigations have shown that smoking ameliorates ulcerative colitis (UC) but exacerbates Crohn's disease (CD), diseases that feature a Th2-mediated and Th1-mediated response, respectively. Cigarette extracts, especially nicotine, affect the Th1/Th2 balance. We previously reported that nicotine protects against mouse DSS colitis (similar to UC) by enhancing microRNA-124 (miR-124) expression. Intriguingly, elevation of miR-124 in CD is reported to aggravate the disease. Here we investigate the dual regulation of miR-124 in inflammatory bowel diseases (IBDs), which may explain the similar bidirectional regulation of tobacco. We found that overexpressed miR-124 protected against mouse DSS-induced colitis with a Th1 polarization in peripheral blood lymphocytes and colon tissues, which was also found in human peripheral blood lymphocytes. Conversely, miR-124 knockdown worsened DSS murine colitis with a Th2 polarization. Moreover, knockdown of miR-124 could eliminate the polarization toward Th1 after nicotine treatment, suggesting that miR-124 mediates the effect of nicotine on the Th1/Th2 balance. In addition, interference of IL-6R, which is a downstream target of miR-124, could remarkably weaken the Th1 polarization induced by miR-124. Taken together, these results suggest that nicotine shifts the balance of Th1/Th2 toward Th1 via a miR-124-mediated IL-6R pathway, which might explain its dual role in IBDs.
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Affiliation(s)
- Zhen Qin
- Department of Clinical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai, China
| | - Peng-Yuan Wang
- Department of Clinical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai, China.,Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, China
| | - Jing-Jing Wan
- Department of Clinical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai, China.,Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, China
| | - Yu Zhang
- Department of Clinical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai, China.,Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, China
| | - Jie Wei
- Department of Clinical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai, China
| | - Yang Sun
- Department of Clinical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai, China
| | - Xia Liu
- Department of Clinical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai, China
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Phloretin ameliorates dextran sulfate sodium-induced ulcerative colitis in mice by regulating the gut microbiota. Pharmacol Res 2019; 150:104489. [PMID: 31689519 DOI: 10.1016/j.phrs.2019.104489] [Citation(s) in RCA: 187] [Impact Index Per Article: 31.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2019] [Revised: 10/04/2019] [Accepted: 10/10/2019] [Indexed: 02/06/2023]
Abstract
Phloretin, extracted from the pericarp and velamen of apples or pears, is a dihydrochalcone flavonoid with anti-bacterial and anti-inflammatory activities. It has been reported that phloretin has anti-inflammatory effects in ulcerative colitis (UC) mice. However, the role of the gut microbiota in the phloretin anti-UC process remains unclear. In this study, we observed that the anti-UC effect of phloretin was affected by co-housing, probably because of the transmissible nature of the gut micobiota. Through fecal micobiota transplantation (FMT), the effects of the gut microbiota on the anti-UC of phloretin were further confirmed. UC was induced in mice by administrating 3% dextran sulfate sodium (DSS) in drinking water for 7 days. Phloretin (60 mg/kg) was administered by gavage every day during the experiment. Fecal microbes (109 CFU/mL) from phloretin-treated UC mice were administered by gavage to non-phloretin-treated UC mice for 7 days. The results showed that FMT, like phloretin, ameliorated UC by improving disease symptoms and colon inflammation, balancing inflammatory cytokines, maintaining intestinal barrier integrity, restoring systemic immune function, inhibiting NF-κB and NLRP3 inflammasome activation and ameliorating the oxidant stress. Both FMT and phloretin treatment increased the levels of Bacteroidetes, Alistipes and Lactobacillus and decreased those of Firmicutes, Oscillibacter and Ruminiclostridium_6. Correlation analysis between gut microbes and micro-environmental factors revealed that Alistipes abundance was negatively correlated with DAI, pathological score, and TNF-α, IL-6 and IL-1β levels, and Alistipes was more abundant in phloretin or FMT treated UC mice. Oscillibacter abundance was significantly positively correlated with IL-6 and IL-1β levels and pathological score, and Oscillibacter was increased in UC mice. Furthermore, network analysis of the dominant genera revealed that Alistipes abundance was negatively related to Oscillibacter abundance. In conclusion, this study suggests that the anti-UC effects of phloretin are achieved through regulation of the gut microbiota and phloretin has the potential to be developed as a promising agent for the treatment of UC.
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Choi YS, Kim JK, Kim WJ, Kim MJ. Remission of diffuse ulcerative duodenitis in a patient with ulcerative colitis after infliximab therapy: a case study and review of the literature. Intest Res 2019; 17:273-277. [PMID: 30739436 PMCID: PMC6505096 DOI: 10.5217/ir.2018.00122] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2018] [Revised: 11/06/2018] [Accepted: 11/07/2018] [Indexed: 12/12/2022] Open
Abstract
Although ulcerative colitis (UC) is confined to colonic and rectal mucosa in a continuous fashion, recent studies have also demonstrated the involvement of upper gastrointestinal tract as diagnostic endoscopy becomes more available and technically advanced. The pathogenesis of UC is not well established yet. It might be associated with an inappropriate response of host mucosal immune system to gut microflora. Although continuous and symmetric distribution of mucosal inflammation from rectum to colon is a typical pattern of UC, clinical feature and course of atypically distributed lesions in UC might also help us understand the pathogenesis of UC. Herein, we report a case of duodenal involvement of UC which successfully remitted after infliximab therapy. Endoscopic and pathologic findings before and after administration of anti-tumor necrosis factor suggest that the pathogenesis of upper gastrointestinal involvement of UC may be similar to that of colon involvement.
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Affiliation(s)
- Yong-Sung Choi
- Department of Gastroenterology, Daehang Hospital, Seoul, Korea
| | - Jong Kyu Kim
- Department of Gastroenterology, Daehang Hospital, Seoul, Korea
| | - Wan Jung Kim
- Department of Gastroenterology, Daehang Hospital, Seoul, Korea
| | - Mi-Jung Kim
- Department of Pathology, Daehang Hospital, Seoul, Korea
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19
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Ku JM, Hong SH, Kim SR, Choi HS, Kim HI, Kim DU, Oh SM, Seo HS, Kim TY, Shin YC, Cheon C, Ko SG. The prevention of 2,4-dinitrochlorobenzene-induced inflammation in atopic dermatitis-like skin lesions in BALB/c mice by Jawoongo. Altern Ther Health Med 2018; 18:215. [PMID: 30005655 PMCID: PMC6045835 DOI: 10.1186/s12906-018-2280-z] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2017] [Accepted: 07/06/2018] [Indexed: 01/09/2023]
Abstract
Background Jawoongo is an herbal mixture used in traditional medicine to treat skin diseases. This study aimed to investigate whether Jawoongo ameliorates Atopic dermatitis (AD)-like pathology in mice and to understand its underlying cellular mechanisms. Methods AD was induced by 2, 4-Dinitrocholrlbenzene (DNCB) in BALB/c mice. Treatment with Jawoongo was assessed to study the effect of Jawoongo on AD in mice. Histological Analysis, blood analysis, RT-PCR, western blot analysis, ELISA assay and cell viability assay were performed to verify the inhibitory effect of Jawoongo on AD in mice. Results We found that application of Jawoongo in an ointment form on AD-like skin lesions on DNCB-exposed BALB/c mice reduced skin thickness and ameliorated skin infiltration with inflammatory cells, mast cells and CD4+ cells. The ointment also reduced the mRNA levels of IL-2, IL-4, IL-13 and TNF-α in the sensitized skin. Leukocyte counts and the levels of IgE, IL-6, IL-10 and IL-12 were decreased in the blood of the DNCB-treated mice. Furthermore, studies on cultured cells demonstrated that Jawoongo exhibits anti-inflammatory activities, including the suppression of proinflammatory cytokine expression, nitric oxide (NO) production, and inflammation-associated molecule levels in numerous types of agonist-stimulated innate immune cell, including human mast cells (HMC-1), murine macrophage RAW264.7 cells, and splenocytes isolated from mice. Conclusion These findings indicate that Jawoongo alleviates DNCB-induced AD-like symptoms via the modulation of several inflammatory responses, indicating that Jawoongo might be a useful drug for the treatment of AD. Electronic supplementary material The online version of this article (10.1186/s12906-018-2280-z) contains supplementary material, which is available to authorized users.
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20
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Abstract
PURPOSE OF REVIEW Ileal pouch-anal anastomosis (IPAA) is the preferred surgical treatment for patients undergoing colectomy to maintain intestinal continuity. Earlier studies have suggested that outcomes are worse in elderly patients who underwent IPAA. However, more recent reports have shown that IPAA outcomes in the elderly are comparable to younger patients. We review the recent medical literature regarding outcomes and treatments for common complications in elderly IPAA patients. RECENT FINDINGS Compared to younger patients, IPAA in the elderly is not associated with increased major surgical complications, but is associated with increased length of stay and re-admission rate for dehydration in older patients. Rates of fecal incontinence after IPAA were similar between younger and older patients. Sacral nerve stimulation has shown early promise as a possible treatment for fecal incontinence after IPAA, but more research is needed. Pouchitis is a common complication, and antibiotics remain first-line treatment options. Other treatment options include mesalamines, steroids, immunomodulators, and biologics. The efficacy of newer biologics such as vedolizumab and ustekinumab has been reported, but more data is needed. IPAA is safe in the elderly with high self-reported patient satisfaction. However, the elderly IPAA patient warrants special consideration regarding outcomes and management.
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Huguet M, Pereira B, Goutte M, Goutorbe F, Dubois A, Bommelaer G, Buisson A. Systematic Review With Meta-Analysis: Anti-TNF Therapy in Refractory Pouchitis and Crohn's Disease-Like Complications of the Pouch After Ileal Pouch-Anal Anastomosis Following Colectomy for Ulcerative Colitis. Inflamm Bowel Dis 2018; 24:261-268. [PMID: 29361101 DOI: 10.1093/ibd/izx049] [Citation(s) in RCA: 74] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Inflammatory complications including chronic refractory pouchitis and Crohn's disease (CD)-like complications of the pouch are common complications after ileal pouch-anal anastomosis (IPAA) following colectomy for ulcerative colitis (UC). We performed a systematic review and meta-analysis to evaluate the efficacy of anti-TNF therapy in distinguishing patients with chronic refractory pouchitis from those with CD-like complications of the pouch. METHODS We performed a systematic literature search to identify articles and abstracts reporting anti-TNF agents efficacy in treating inflammatory complications of the pouch after IPAA for UC. Short-term and long-term remissions were evaluated at 8 weeks 95%CI[5-10] and 12 months 95%CI[12-18.5], respectively. RESULTS We identified 21 articles and 3 abstracts including 313 patients treated either with infliximab (n = 194) or adalimumab (n = 119) for inflammatory complications of the pouch. The rates of short-term and long-term clinical remission were 0.50 (95%CI [0.37-0.63]; I2 = 0.57) and 0.52 (95%CI[0.39-0.65]; I2 = 0.59), respectively. The rate of remission after anti-TNF induction therapy seemed to be higher in CD-like complications of the pouch 0.64 (95%CI[0.5-0.77]; I2 = 0.18), compared to refractory pouchitis 0.10 (95%CI [0.00-0.35]; I2 = 0.00) (P = 0.06), whereas no such difference appeared after long-term maintenance therapy 0.57 (95%CI[0.43-0.71]; I2 = 0.32) and 0.37 (95%CI [0.14-0.62]; I2 = 0.47), respectively (P = 0.57). Sensitivity analyses suggested no difference in outcomes. No significant publication bias has been detected. CONCLUSION Anti-TNF agents have a clear trend to have higher and faster efficacy in CD-like complications of the pouch compared to refractory pouchitis, highlighting the need to differentiate these two entities both in daily practice and clinical trials.
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Affiliation(s)
- Mathilde Huguet
- Université Clermont Auvergne, Inserm, 3iHP, CHU Clermont-Ferrand, Service d'Hépato-Gastro Entérologie, Clermont-Ferrand, France
| | - Bruno Pereira
- Biostatistics Unit- DRCI, GM - Clermont-Ferrand University and Medical Center, Clermont-Ferrand, France
| | - Marion Goutte
- Université Clermont Auvergne, Inserm, 3iHP, CHU Clermont-Ferrand, Service d'Hépato-Gastro Entérologie, Clermont-Ferrand, France
- Université Clermont Auvergne, Inserm U1071, M2iSH, USC-INRA 2018, F-63000 Clermont-Ferrand, France
| | - Félix Goutorbe
- Université Clermont Auvergne, Inserm, 3iHP, CHU Clermont-Ferrand, Service d'Hépato-Gastro Entérologie, Clermont-Ferrand, France
| | - Anne Dubois
- Université Clermont Auvergne, CHU Clermont-Ferrand, Service de chirurgie digestive, Clermont-Ferrand, France
| | - Gilles Bommelaer
- Université Clermont Auvergne, Inserm, 3iHP, CHU Clermont-Ferrand, Service d'Hépato-Gastro Entérologie, Clermont-Ferrand, France
- Université Clermont Auvergne, Inserm U1071, M2iSH, USC-INRA 2018, F-63000 Clermont-Ferrand, France
| | - Anthony Buisson
- Université Clermont Auvergne, Inserm, 3iHP, CHU Clermont-Ferrand, Service d'Hépato-Gastro Entérologie, Clermont-Ferrand, France
- Université Clermont Auvergne, Inserm U1071, M2iSH, USC-INRA 2018, F-63000 Clermont-Ferrand, France
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Garidisan: Improving the Quality of Ulcer Healing in Rats with Ulcerative Colitis. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2017; 2017:8721257. [PMID: 28928792 PMCID: PMC5591922 DOI: 10.1155/2017/8721257] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/08/2017] [Revised: 05/21/2017] [Accepted: 06/06/2017] [Indexed: 12/16/2022]
Abstract
Garidisan, commonly used in Mongolia to treat ulcerative colitis (UC), contains wild poppy and Artemisia frigida Willd. Clinical evidence shows that Garidisan can effectively treat UC and that recurrence is low. Thus, we evaluated the effects of Garidisan on ulcer healing quality and the regulation of immune balance in rats with experimental UC. UC was induced by immunization with TNBS and Garidisan significantly reduced DAI, CMDI, and HS. H&E staining, SEM, and VG staining showed that Garidisan repaired damaged intestinal mucosa and significantly reduced expression of ICAM-1 and CD105 in regenerated tissues of UC rats. Collagen fibers were significantly fewer as well after treatment. Garidisan elevated EGF, VEGF, bFGF, VEGFR2, and FGFR1 of UC rats, reduced CD3+CD4+/CD3+CD8+ T cell ratios, and increased CD4+Th1/CD4+Th2 cell ratios and IFN-r/IL-4 ratios in peripheral blood of UC rats. In conclusion, Garidisan promoted tissue maturation of regenerated tissues by regulating the immune balance and improved functional maturity of regenerated tissues by reducing collagen formation, promoting maturation of new blood vessels, and increasing expression of growth factors and their receptors.
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Abstract
Data about the effectiveness of biologics, including anti-tumor necrosis factor (TNF) therapy and anti-integrin strategies, in antibiotic refractory pouchitis or Crohn's disease-associated pouch complications are sparse. We performed a systematic review of the literature in Medline and Web of Science. All English language publications and meeting abstracts describing patients with pouchitis treated with anti-TNF or anti-integrin therapies were included. We identified a total of 17 papers and 2 abstracts, most of these retrospective case series, including a total of 192 patients treated either with infliximab (n=140) or adalimumab (n=52). No reports were found for anti-integrin therapies or other anti-TNF agents such as certolizumab pegol or golimumab. Because of the heterogeneity of the studies, small numbers of patients, differing cotreatments, and subjective outcome definitions, the exact efficacy of these biological therapies cannot be assessed in a combined fashion. Overall infliximab appears to have good clinical effectiveness in selected patients achieving up to 80% short-term and around 50% long-term response, whereas the few data available for adalimumab are not sufficient to draw valid conclusions. Larger prospectively collected multicenter data with clearly defined inclusion criteria and outcomes are necessary to better define the clinical value of anti-TNF therapy in patients with antibiotic refractory pouchitis or Crohn's-like complications of the pouch.
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Ming Z, Jia Y, Yan Y, Pang G, Chen Q. Amelioration effect of bovine casein glycomacropeptide on ulcerative colitis in mice. FOOD AGR IMMUNOL 2015. [DOI: 10.1080/09540105.2015.1018874] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022] Open
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Tacrolimus Therapy for Ulcerative Colitis-Associated Post-Colectomy Enteritis. ACG Case Rep J 2014; 2:33-5. [PMID: 26157899 PMCID: PMC4435352 DOI: 10.14309/crj.2014.76] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2013] [Accepted: 07/30/2014] [Indexed: 12/20/2022] Open
Abstract
Ulcerative colitis (UC)-associated pan-enteritis is a newly identified clinical entity that occurs almost exclusively after colectomy. Characterized by diffuse small bowel mucosal inflammation not compatible with Crohn's disease, the optimal treatment modality for this condition is unknown. Tacrolimus is a potent calcineurin inhibitor that has been successfully used in the treatment of UC. We describe a case of severe refractory pan-enteritis after colectomy for UC that was successfully treated with oral tacrolimus after failing intravenous corticosteroid treatment. Tacrolimus may be a safe and effective treatment modality for diffuse enteritis after colectomy in UC patients.
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Chiba M, Ono I, Wakamatsu H, Wada I, Suzuki K. Diffuse gastroduodenitis associated with ulcerative colitis: treatment by infliximab. Dig Endosc 2013; 25:622-5. [PMID: 24164601 DOI: 10.1111/j.1443-1661.2012.01398.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2012] [Accepted: 09/06/2012] [Indexed: 01/21/2023]
Abstract
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.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.
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Affiliation(s)
- Mitsuro Chiba
- Division of Gastroenterology, Nakadori General Hospital
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Hoentjen F, Hanauer SB, Hart J, Rubin DT. Long-term treatment of patients with a history of ulcerative colitis who develop gastritis and pan-enteritis after colectomy. J Clin Gastroenterol 2013; 47:52-7. [PMID: 22858512 PMCID: PMC3874322 DOI: 10.1097/mcg.0b013e3182582c1d] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Ulcerative colitis (UC) is generally described as a superficial diffuse inflammation restricted to the colon and rectum. However, several case reports have described a distinct and rare type of UC-related pan-enteritis, typically occurring after colectomy. Corticosteroids are effective for induction of remission of this condition, but it is not clear how these patients should be managed long term. GOALS To further describe and define the entity of UC-related pan-enteritis and to investigate the efficacy of azathioprine for maintenance of remission. RESULTS We describe 5 patients with superficial diffuse ulcerative inflammation of the stomach, small bowel, and pouch if present. Four of the 5 patients developed enteritis after colectomy for ulcerative pancolitis. Pathology showed severe mucosal inflammation with infiltration of neutrophils and plasma cells from the stomach to the ileum. Video capsule endoscopy in 1 patient confirmed the presence of mucosal inflammation throughout the small bowel. All patients were started on a standardized treatment with intravenous corticosteroids for induction of remission and azathioprine for maintenance therapy. The conditions of all the patients rapidly improved, and subsequently, 4 patients were in full remission on azathioprine monotherapy, despite failure of this UC therapy before surgery, whereas 1 patient continues to have a steroid-dependent disease. CONCLUSIONS The outcomes of 5 cases of UC-related pan-enteritis as described in this report support a role for azathioprine in remission maintenance. Future research is needed to improve our understanding of this rare but distinct intestinal inflammatory disorder.
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Affiliation(s)
- Frank Hoentjen
- Inflammatory Bowel Disease Center, University of Chicago Medical Center, Chicago, USA,Inflammatory Bowel Disease Center, Department of Gastroenterology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Stephen B. Hanauer
- Inflammatory Bowel Disease Center, University of Chicago Medical Center, Chicago, USA
| | - John Hart
- Department of Pathology, University of Chicago Medical Center, Chicago, USA
| | - David T. Rubin
- Inflammatory Bowel Disease Center, University of Chicago Medical Center, Chicago, USA
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Götlind YY, Fritsch Fredin M, Kumawat AK, Strid H, Willén R, Rangel I, Bland PW, Hörnquist EH. Interplay between T(h)1 and T(h)17 effector T-cell pathways in the pathogenesis of spontaneous colitis and colon cancer in the Gαi2-deficient mouse. Int Immunol 2013; 25:35-44. [PMID: 22962436 DOI: 10.1093/intimm/dxs089] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Gαi2-deficient mice spontaneously develop colitis. Using xMAP technology and RT-PCR, we investigated cytokine/chemokine profiles during histologically defined phases of disease: (i) no/mild, (ii) moderate, (iii) severe colitis without dysplasia/cancer and (iv) severe colitis with dysplasia/cancer, compared with age-matched wild-type (WT) littermates. Colonic dysplasia was observed in 4/11 mice and cancer in 1/11 mice with severe colitis. The histology correlated with progressive increases in colon weight/cm and spleen weight, and decreased thymus weight, all more advanced in mice with dysplasia/cancer. IL-1β, IL-6, IL-12p40, IL-17, TNF-α, CCL2 and CXCL1 protein levels in colons, but not small intestines increased with colitis progression and were significantly increased in mice with moderate and severe colitis compared with WT mice, irrespective of the absence/presence of dysplasia/cancer. CCL5 did not change during colitis progression. Colonic IL-17 transcription increased 40- to 70-fold in all stages of colitis, whereas IFN-γ mRNA was gradually up-regulated 12- to 55-fold with colitis progression, and further to 62-fold in mice with dysplasia/cancer. IL-27 mRNA increased 4- to 15-fold during the course of colitis, and colonic IL-21 transcription increased 3-fold in mice with severe colitis, both irrespective of the absence/presence of dysplasia/cancer. FoxP3 transcription was significantly enhanced (3.5-fold) in mice with moderate and severe colitis, but not in mice with dysplasia/cancer, compared with WT mice. Constrained correspondence analysis demonstrated an association between increased protein levels of TNF-α, CCL2, IL-1β, IL-6 and CXCL1 and dysplasia/cancer. In conclusion, colonic responses are dominated by a mixed T(h)1/T(h)17 phenotype, with increasing T(h)1 cytokine transcription with progression of colitis in Gαi2(-/-) mice.
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Affiliation(s)
- Yu-Yuan Götlind
- Department of Microbiology and Immunology, Institute of Biomedicine and MIVAC, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden
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Godoi DF, Cardoso CR, Silva MJB, Ferraz DB, Provinciatto PR, Cunha FDQ, da Silva JS, Voltarelli JC. Reappraisal of total body irradiation followed by bone marrow transplantation as a therapy for inflammatory bowel disease. Immunobiology 2012; 218:317-24. [PMID: 22771114 DOI: 10.1016/j.imbio.2012.05.012] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2012] [Accepted: 05/16/2012] [Indexed: 01/14/2023]
Abstract
The main current therapies for inflammatory bowel diseases (IBD) are aimed at controlling the exacerbated inflammation in the gut. Although these therapies have been successful, they are not curative and it is not possible to predict whether a beneficial response will occur or which patients will be refractory to the treatment. Total body irradiation (TBI) associated with chemotherapy is the first choice in the treatment of some hematological disorders and is an applicable option in the preparation of patients with hematologic diseases for hematopoietic stem cell transplantation. Then, in this study we investigated the association of TBI as immunosuppressive therapy and bone marrow cell (BMC) transplantation as a strategy to induce colitis recovery and immune reconstitution in the TNBS model of intestinal inflammation. TNBS mice treated with TBI associated with BMC transplantation presented elevated gain of weight and an overall better outcome of the disease when compared to those treated only with TBI. In addition, TBI associated or not with BMC reduced the frequency of inflammatory cells in the gut and restored the goblet cell counts. These results were accompanied by a down regulation in the production of inflammatory cytokines in the colon of mice treated with TBI alone or in association with BMC transplantation. The BMC infused were able to repopulate the ablated immune system and accumulate in the site of inflammation. However, although both treatments (TBI or TBI+BMC) were able to reduce gut inflammation, TBI alone was not enough to fully restore mice weight and these animals presented an extremely reduced survival rate when their immune system was not promptly reconstituted with BMC transplantation. Finally, these evidences suggest that the BMC transplantation is an efficient strategy to reduce the harmful effects of TBI in the colitis treatment, suggesting that radiotherapy may be an important immunosuppressive therapy in patients with IBD, by modulating the local inflammatory response.
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Affiliation(s)
- Dannielle Fernandes Godoi
- Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
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