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Prasad G, Kulkarni K, Dhua AK, Malik R. Chronic enteropathy associated with SLCO2A1 from North India: a rare monogenic condition mimicking Crohn's disease. BMJ Case Rep 2025; 18:e263684. [PMID: 39842898 DOI: 10.1136/bcr-2024-263684] [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: 01/24/2025] Open
Abstract
Multiple chronic ulcers of the small intestine are primarily attributed to Crohn's disease. Other differential diagnoses include rare monogenic disorders caused by mutations in PLA2G4A and SLCO2A1, the latter responsible for chronic enteropathy associated with SLCO2A1 (CEAS), a condition mainly reported in Asian patients. We present the case of a 10-year-old girl from India with a 5-year history of abdominal pain, altered bowel habits and failure to gain weight. Despite multiple admissions and treatment with steroids, immunomodulators and biologics, her symptoms persisted. Exome sequencing confirmed CEAS, and radiographic imaging revealed multiple strictures in the small intestine, confirmed during laparotomy. Multiple Heineke-Mikulicz type strictureplasties were performed. This case underscores the importance of considering CEAS in patients with recurrent small intestinal ulcerations, particularly in the presence of concentric strictures, and highlights the role of genetic testing for SLCO2A1 mutations.
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Affiliation(s)
- Gaurav Prasad
- Paediatric Surgery, All India Institute of Medical Sciences, New Delhi, India
| | - Kaushal Kulkarni
- Paediatric Surgery, All India Institute of Medical Sciences, New Delhi, India
| | - Anjan Kumar Dhua
- Paediatric Surgery, All India Institute of Medical Sciences, New Delhi, India
| | - Rohan Malik
- Pediatrics, All India Institute of Medical Sciences, New Delhi, Delhi, India
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Bencardino S, Allocca M, Furfaro F, D'Amico F, Parigi TL, Danese S, Zilli A. Multiple Ileal and Colonic Stenoses: Is It Always Crohn's Disease? J Crohns Colitis 2024:jjae174. [PMID: 39679549 DOI: 10.1093/ecco-jcc/jjae174] [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] [Indexed: 12/17/2024]
Abstract
A 62-year-old woman presented with multiple ileal and colonic stenoses, initially suspected to be Crohn's disease. Despite unremarkable endoscopic biopsies, surgery was performed due to clinical deterioration, and histological analysis confirmed the presence of metastatic breast cancer. This case highlights the importance of considering metastatic disease in the differential diagnosis of gastrointestinal (GI) strictures, particularly when inflammatory bowel disease markers are inconclusive or marginal. Clinicians should be aware of the potential for breast cancer to metastasize to the GI tract, which may present with symptoms mimicking primary GI diseases.
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Affiliation(s)
- Sarah Bencardino
- Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
| | - Mariangela Allocca
- Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
| | - Federica Furfaro
- Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
| | - Ferdinando D'Amico
- Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
| | - Tommaso Lorenzo Parigi
- Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
| | - Silvio Danese
- Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
| | - Alessandra Zilli
- Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
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Bhowmick M, Sharma V. Cryptogenic multifocal ulcerous stenosing enteritis: A ray of light on the umbra of the dark continent. Indian J Gastroenterol 2024; 43:1082-1085. [PMID: 39023741 DOI: 10.1007/s12664-024-01645-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/20/2024]
Affiliation(s)
- Mithu Bhowmick
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Vishal Sharma
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India.
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Mettananda S, Bandara P, Rajeindran M, Padeniya P. A novel mutation in the SLCO2A1 gene presenting as persistent hypoproteinaemia and refractory iron deficiency anaemia due to chronic enteropathy: a case report. BMC Pediatr 2024; 24:751. [PMID: 39563252 DOI: 10.1186/s12887-024-05252-6] [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: 05/05/2024] [Accepted: 11/14/2024] [Indexed: 11/21/2024] Open
Abstract
BACKGROUND The SLCO2A1 gene encodes a prostaglandin transporter and we report a novel mutation causing hypoproteinaemia and refractory anaemia due to chronic enteropathy. CASE PRESENTATION An 18-year-old boy of consanguineous parents was investigated for hypoproteinaemia and anaemia. He was short, pale and had generalised oedema. Investigations revealed haemoglobin 5.8 g/dL; hypochromic microcytic anaemia; low serum protein, albumin, globulin, ferritin and iron. Bone marrow aspiration revealed low iron stores. Upper and lower gastrointestinal endoscopies showed moderate gastritis, duodenitis, and non-specific patchy inflammation in the rectum. The whole exome sequencing revealed a homozygous missense mutation in SCLO2A1 gene (NP_005621.2:p.Arg97Cys; rs761212094). Sanger sequencing of the sibling with milder phenotype revealed same homozygous mutation, and carrier father was heterozygous. CONCLUSION We report a novel mutation of SLCO2A1 gene causing severe persistent hypoproteinaemia and refractory iron deficiency anaemia due to chronic enteropathy helping to delineate genotype-phenotype correlation of SLCO2A1 variants.
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Affiliation(s)
- Sachith Mettananda
- Colombo North Teaching Hospital, Ragama, Sri Lanka.
- Department of Paediatrics, Faculty of Medicine, University of Kelaniya, Thalagolla Road, Ragama, 11010, Sri Lanka.
| | | | - Manissha Rajeindran
- Department of Bionformatics, Credence Genomics (Pvt) Ltd, Colombo, Sri Lanka
| | - Padmapani Padeniya
- Department of Anatomy, Faculty of Medicine, University of Kelaniya, Colombo, Sri Lanka
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Lim JG, Ko JS, Ko JM, Kim HY, Kim MJ, Seong MW, Choi YH, Kang GH, Koh J, Moon JS. Characteristics of chronic enteropathy associated with SLCO2A1 gene (CEAS) in children, a unique type of monogenic very early-onset inflammatory bowel disease. BMC Pediatr 2024; 24:396. [PMID: 38890589 PMCID: PMC11184885 DOI: 10.1186/s12887-024-04877-x] [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: 02/28/2024] [Accepted: 06/10/2024] [Indexed: 06/20/2024] Open
Abstract
BACKGROUND Chronic enteropathy associated with SLCO2A1 gene (CEAS) is a unique type of inflammatory bowel disease. CEAS is monogenic disease and is thought to develop from childhood, but studies on pediatric CEAS are scarce. We analyzed characteristics of pediatric CEAS. METHODS Eleven patients diagnosed with CEAS at Seoul National University Children's Hospital were identified and analyzed. Clinical data of patients were collected. Sanger sequencing of SLCO2A1 was performed on all patients. RESULTS Patients were diagnosed at a median age of 16.0 years (IQR 11.0 ~ 20.0), and the median age at symptoms onset was only 4.0 years (IQR 2.5 ~ 6.0). Growth delay was observed at the time of diagnosis. Patients showed multiple ulcers or strictures in the small intestine, while the esophagus and colon were unaffected in any patients. Almost half of the patients underwent small intestine resection. The major laboratory features of pediatric CEAS include iron deficiency anemia (IDA), hypoalbuminemia, and near-normal levels of C-reactive protein (CRP). Two novel mutations of SLCO2A1 were identified. The most prevalent symptoms were abdominal pain and pale face. None of the immunomodulatory drugs showed a significant effect on CEAS. CONCLUSIONS Pediatric CEAS typically develop from very young age, suggesting it as one type of monogenic very early onset inflammatory bowel disease. CEAS can cause growth delay in children but there is no effective treatment currently. We recommend screening for SLCO2A1 mutations to pediatric patients with chronic IDA from a young age and small intestine ulcers without elevation of CRP levels.
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Affiliation(s)
- Jin Gyu Lim
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Children's Hospital, 101 Daehak-Ro, Jongno-Gu, Seoul, 03080, Korea
| | - Jae Sung Ko
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Children's Hospital, 101 Daehak-Ro, Jongno-Gu, Seoul, 03080, Korea
| | - Jung Min Ko
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Children's Hospital, 101 Daehak-Ro, Jongno-Gu, Seoul, 03080, Korea
| | - Hyun Young Kim
- Department of Pediatric Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Man Jin Kim
- Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Moon Woo Seong
- Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Young Hun Choi
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Gyeong Hoon Kang
- Department of Pathology, Seoul National University College of Medicine, Seoul, Korea
| | - Jaemoon Koh
- Department of Pathology, Seoul National University College of Medicine, Seoul, Korea
| | - Jin Soo Moon
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Children's Hospital, 101 Daehak-Ro, Jongno-Gu, Seoul, 03080, Korea.
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Dai Y, He M, Xu H, Tan B, Zhou W, Liu W, Wang Q, Huang J, Shang Q, Liu Y, Li Y. A novel variant in the SLCO2A1 gene in a Chinese patient with chronic gastroenteropathy and primary hypertrophic osteoarthropathy. Orphanet J Rare Dis 2024; 19:229. [PMID: 38862970 PMCID: PMC11165838 DOI: 10.1186/s13023-024-03221-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Accepted: 05/19/2024] [Indexed: 06/13/2024] Open
Abstract
BACKGROUND Chronic enteropathy associated with SLCO2A1 gene (CEAS) results from loss-of-function variants in SLCO2A1, which encodes the prostaglandin transporter (PGT). CEAS follows an autosomal recessive inheritance pattern. To date, approximate 30 pathogenic variants have been reported in CEAS. METHODS We performed whole exome sequencing (WES) to screen for potential pathogenic variants in a patient suspected of having CEAS, and confirmed a variant in SLCO2A1 using Sanger sequencing. We established an in vitro minigene model to compare splicing between wild type (WT) and mutant transcripts. Quantitative polymerase chain reaction (qPCR) was used to evaluate SLCO2A1 transcription in the stomach and colon tissues from the patient and a healthy control (HC). The transcripts were further cloned and sequenced. RESULTS The patient had a novel, homozygous, recessive c.929A > G variant in exon 7 of SLCO2A1, which has not been previously reported in CEAS or PHO. This variant altered splicing, resulting in an exon 7-truncated transcript lacking 16 bases. No normal transcript was detected in the patient's stomach or colon tissue. qPCR also showed significantly decreased SLCO2A1 transcription compared to HC. CONCLUSION A previously unreported variant caused defective SLCO2A1 splicing and reduced mRNA levels in a patient with CEAS and PHO. This research enhances understanding of CEAS and PHO pathophysiology and aids genetic counseling and diagnosis.
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Affiliation(s)
- Yimin Dai
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1, Shuaifuyuan, Beijing, 100730, China
| | - Miao He
- McKusick-Zhang Center for Genetic Medicine, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | | | - Bei Tan
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1, Shuaifuyuan, Beijing, 100730, China
| | - Weixun Zhou
- Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China
| | - Wei Liu
- Department of Radiology, Peking Union Medical College Hospital, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 1, Shuaifuyuan, Beijing, 100730, China
| | - Qiang Wang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1, Shuaifuyuan, Beijing, 100730, China
| | - Jingyi Huang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1, Shuaifuyuan, Beijing, 100730, China
| | - Qing Shang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1, Shuaifuyuan, Beijing, 100730, China
| | - Yaping Liu
- The State Key Laboratory for Complex, Severe, and Rare Diseases, The State Key Sci-tech Infrastructure for Translational Medicine, Peking Union Medical College Hospital, Beijing, 100730, China.
| | - Yue Li
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1, Shuaifuyuan, Beijing, 100730, China.
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Xie ZX, Li Y, Yang AM, Wu D, Wang Q. Pathogenesis of chronic enteropathy associated with the SLCO2A1 gene: Hypotheses and conundrums. World J Gastroenterol 2024; 30:2505-2511. [PMID: 38817656 PMCID: PMC11135407 DOI: 10.3748/wjg.v30.i19.2505] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2024] [Revised: 03/18/2024] [Accepted: 04/25/2024] [Indexed: 05/20/2024] Open
Abstract
Chronic enteropathy associated with the SLCO2A1 gene (CEAS) is a complex gastroenterological condition characterized by multiple ulcers in the small intestine with chronic bleeding and protein loss. This review explores the potential mechanisms underlying the pathogenesis of CEAS, focusing on the role of SLCO2A1-encoded prostaglandin transporter OATP2A1 and its impact on prostaglandin E2 (PGE2) levels. Studies have suggested that elevated PGE2 levels contribute to mucosal damage, inflammation, and disruption of the intestinal barrier. The effects of PGE2 on macrophage activation and Maxi-Cl channel functionality, as well as its interaction with nonsteroidal anti-inflammatory drugs play crucial roles in the progression of CEAS. Understanding the balance between its protective and pro-inflammatory effects and the complex interactions within the gastrointestinal tract can shed light on potential therapeutic targets for CEAS and guide the development of novel, targeted therapies.
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Affiliation(s)
- Zhi-Xin Xie
- State Key Laboratory of Complex Severe and Rare Diseases, Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China
- Department of Clinical Medicine, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Yue Li
- State Key Laboratory of Complex Severe and Rare Diseases, Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Ai-Ming Yang
- State Key Laboratory of Complex Severe and Rare Diseases, Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Dong Wu
- State Key Laboratory of Complex Severe and Rare Diseases, Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Qiang Wang
- State Key Laboratory of Complex Severe and Rare Diseases, Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China
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8
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Shang Q, Dai Y, Huang J, Liu W, Zhou W, Liu Y, Yang H, Wang Q, Li Y. Clinical and genetic characteristics of Chinese patients diagnosed with chronic enteropathy associated with SLCO2A1 gene. Orphanet J Rare Dis 2024; 19:201. [PMID: 38755710 PMCID: PMC11100163 DOI: 10.1186/s13023-024-03177-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Accepted: 03/30/2024] [Indexed: 05/18/2024] Open
Abstract
BACKGROUND AND AIMS Chronic enteropathy associated with SLCO2A1 gene is a rare intestinal disease caused by loss-of-function SLCO2A1 mutations, with clinical and genetic characteristics remaining largely unknown, especially in Chinese patients. This study aims to reveal clinical and genetic features of Chinese CEAS patients, highlighting the previously unreported or unemphasized characteristics. METHODS We enrolled 12 Chinese patients with chronic enteropathy associated with SLCO2A1 gene admitted to Peking Union Medical College Hospital from January 2018 to December 2022. Clinical and genetic data of these patients were collected and analyzed. RESULTS 58.3% of patients were male, who also had primary hypertrophic osteoarthropathy, whereas female patients did not have primary hypertrophic osteoarthropathy. Apart from common symptoms associated with anemia and hypoalbuminemia, abdominal pain, ileus, diarrhea, and hematochezia were present. 4 of the 5 female patients had early-onset amenorrhea, though the causal relationship remained to be clarified. Endoscopy and computed tomography enterography revealed that lesions can occur in any part of the digestive tract, most commonly in the ileum. Pathology showed multiple superficial ulcers with adjacent vascular dilatation, and loss of SLCO2A1 expression, particularly in gastrointestinal vascular endothelial cells. Genetic analysis confirmed SLCO2A1 mutations in all patients and identified 11 new SLCO2A1 variants for CEAS. CONCLUSIONS This study reports new clinical, pathological, and genetic findings in 12 Chinese patients with chronic enteropathy associated with SLCO2A1 gene. This study provides insights into the pathogenesis of this disease. However, studies with larger sample sizes and more in-depth mechanism research are still required.
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Affiliation(s)
- Qing Shang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
- School of Medicine, Tsinghua University, Beijing, 100084, China
| | - Yimin Dai
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Jingyi Huang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Wei Liu
- Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Weixun Zhou
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Yaping Liu
- McKusick-Zhang Center for Genetic Medicine, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking, Union Medical College, Beijing, 100730, China
| | - Hong Yang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Qiang Wang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
| | - Yue Li
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
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Niizeki H, Tanaka R, Nomura T, Seki A, Miyasaka M, Matsumoto Y, Ishibashi M, Narumi S, Nakabayashi K, Yoshida K. Lack of cutis verticis gyrata is associated with c.1279_1290del12 of SLCO2A1 in 43 Japanese patients with pachydermoperiostosis. J Dermatol Sci 2024; 114:86-88. [PMID: 38644096 DOI: 10.1016/j.jdermsci.2024.03.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Revised: 02/22/2024] [Accepted: 03/21/2024] [Indexed: 04/23/2024]
Affiliation(s)
- H Niizeki
- Division of Dermatology, National Center for Child Health and Development, Tokyo, Japan.
| | - R Tanaka
- Division of Dermatology, National Center for Child Health and Development, Tokyo, Japan
| | - T Nomura
- Department of Dermatology, Graduate School of Medicine and Faculty of Medicine, Kyoto University, Kyoto, Japan
| | - A Seki
- Division of Orthopedics, National Center for Child Health and Development, Tokyo, Japan
| | - M Miyasaka
- Division of Radiology, National Center for Child Health and Development, Tokyo, Japan
| | - Y Matsumoto
- Division of Dermatology, National Center for Child Health and Development, Tokyo, Japan
| | - M Ishibashi
- Department of Dermatology, Graduate School of Medicine and Faculty of Medicine, Kyoto University, Kyoto, Japan
| | - S Narumi
- Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan
| | - K Nakabayashi
- Department of Maternal-Fetal Biology, National Research Institute for Child Health and Development, Tokyo, Japan
| | - K Yoshida
- Division of Dermatology, National Center for Child Health and Development, Tokyo, Japan.
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Saura R, Hagiwara SI, Hizuka K, Okamoto N, Etani Y. First case report of dichorionic diamniotic twins with chronic enteropathy associated with the SLCO2A1 gene. Clin J Gastroenterol 2024; 17:240-243. [PMID: 38289459 DOI: 10.1007/s12328-023-01912-9] [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: 11/11/2023] [Accepted: 12/16/2023] [Indexed: 03/24/2024]
Abstract
We report the case of twins diagnosed with chronic enteropathy associated with the SLCO2A1 gene (CEAS) based on characteristic ulcer findings, which required 8 years to diagnose. Both twins had similar symptoms, including anemia and growth failure but the gastrointestinal tract was not evaluated initially because of mild symptoms that were considered consistent with psychological etiology. The endoscopic findings of the firstborn child showed spiral ulcer scars and pseudodiverticulum formation without Helicobacter pylori infection or eosinophilic infiltration in the duodenum. Since the twins presented with ulcers of an unknown cause simultaneously and the first-born child had a spiral ulcer, CEAS was suspected. Genetic analysis and high levels of prostaglandin E major urinary metabolites in the urine led to a definitive diagnosis of CEAS.
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Affiliation(s)
- Ryutaro Saura
- Department of Pediatric Gastroenterology, Nutrition and Endocrinology, Osaka Women's and Children's Hospital, 840 Murodo-cho, Izumi, Osaka, 594-1101, Japan
| | - Shin-Ichiro Hagiwara
- Department of Pediatric Gastroenterology, Nutrition and Endocrinology, Osaka Women's and Children's Hospital, 840 Murodo-cho, Izumi, Osaka, 594-1101, Japan.
| | - Keinosuke Hizuka
- Department of Pediatric Gastroenterology, Nutrition and Endocrinology, Osaka Women's and Children's Hospital, 840 Murodo-cho, Izumi, Osaka, 594-1101, Japan
| | - Nobuhiko Okamoto
- Department of Medical Genetics, Osaka Women's and Children's Hospital, 840 Murodo-cho, Izumi, Osaka, 594-1101, Japan
| | - Yuri Etani
- Department of Pediatric Gastroenterology, Nutrition and Endocrinology, Osaka Women's and Children's Hospital, 840 Murodo-cho, Izumi, Osaka, 594-1101, Japan
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11
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Kimball TN, Rivero-García P, Barrera-Godínez A, Domínguez-Cherit J. Genotype and phenotype characterization of primary hypertrophic osteoarthropathy type 2 and chronic enteropathy associated with SLCO2A1: Report of two cases and literature review. Am J Med Genet A 2024; 194:e63446. [PMID: 37915296 DOI: 10.1002/ajmg.a.63446] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2023] [Revised: 09/22/2023] [Accepted: 10/06/2023] [Indexed: 11/03/2023]
Abstract
Autosomal recessive type 2 primary hypertrophic osteoarthropathy (PHOAR2) and chronic enteropathy associated with SLCO2A1 (CEAS) are two entities caused by pathogenic variants (PVs) in the SLCO2A1 gene that can coexist or occur independently from one another. We report two cases of PHOAR2 in Mexico with concomitant CEAS and conducted a review of the literature of the reported cases of PHOAR2 and/or CEAS to analyze the relationship between their genotype and phenotype presentation. The patients from our Institution with classical PHOAR2 phenotype and CEAS, harbored SLCO2A1 c.547G > A and c.1768del variants. We reviewed 232 cases, of which 86.6% were of Asian origin, and identified 109 different variants in SLCO2A1. Intron 7, exon 13, and exon 4 were predominantly affected. The two most common PVs were c.940 + 1G > A and c.1807C > T. We found a statistically significant association between SLCO2A1 variants located in intron 7, exons 12, and 13 and the development of CEAS. Missense variants were more frequent in isolated PHOAR2, while a greater proportion of protein-truncating variants (PTVs) were found in CEAS. Further investigation is imperative to elucidate the underlying pathophysiological mechanisms associated with CEAS, thereby facilitating the identification of effective therapeutic interventions.
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Affiliation(s)
- Tamara N Kimball
- Department of Genetics, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Pamela Rivero-García
- Department of Genetics, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Alejandro Barrera-Godínez
- Department of Dermatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Judith Domínguez-Cherit
- Department of Dermatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
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Ito N, Kudo T, Eguchi H, Jimbo K, Furuhata A, Okuno T, Takeuchi I, Arai K, Ishige T, Okazaki Y, Shimizu T. Attenuated Expression of SLCO2A1 Caused by DNA Methylation in Pediatric Inflammatory Bowel Disease. Inflamm Bowel Dis 2023; 29:1920-1928. [PMID: 37327083 DOI: 10.1093/ibd/izad116] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Indexed: 06/18/2023]
Abstract
BACKGROUND SLCO2A1 encodes a prostaglandin (PG) transporter, and autosomal recessive pathogenic variants of this gene cause chronic enteropathy associated with SLCO2A1. It is unclear whether a heterozygous pathogenic variant of SLCO2A1 has a role in the pathogenesis of other types of inflammatory bowel disease (IBD). In this study, we investigated the possible involvement of a local epigenetic alteration in SLCO2A1 in patients with a heterozygous pathogenic variant. METHODS We conducted whole-exome sequencing of samples from 2 sisters with suspected monogenic IBD. In addition, we performed bisulfite sequencing using DNA extracted from their small and large intestine samples to explore epigenetic alterations. RESULTS A heterozygous splicing site variant, SLCO2A1:c.940 + 1G > A, was detected in both patients. To explore the possible involvement of epigenetic alterations, we analyzed protein and messenger RNA expression of SLCO2A1, and observed attenuated SLCO2A1 expression in the inflamed lesions of these patients compared with that in the control individuals. Furthermore, bisulfite sequencing indicated dense methylation in the promoter region of SLCO2A1 only in the inflamed lesions of both patients. The urinary PG metabolite levels in these patients were comparable to those in patients with chronic enteropathy associated with SLCO2A1 and higher than those in the control individuals. We found considerably higher levels of the metabolites in patient 1, who showed more severe symptoms than patient 2. CONCLUSIONS Local DNA methylation attenuated SLCO2A1 expression, which may evoke local inflammation of the mucosa by the unincorporated PG. These findings may improve our understanding of the epigenetic mechanisms underlying IBD development.
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Affiliation(s)
- Natsuki Ito
- Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
- Diagnostics and Therapeutics of Intractable Diseases and Intractable Disease Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Takahiro Kudo
- Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Hidetaka Eguchi
- Diagnostics and Therapeutics of Intractable Diseases and Intractable Disease Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Keisuke Jimbo
- Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Atsushi Furuhata
- Biomedical Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Toshiaki Okuno
- Department of Biochemistry, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Ichiro Takeuchi
- Center for Pediatric Inflammatory Bowel Disease, Division of Gastroenterology, National Center for Child Health and Development, Tokyo, Japan
| | - Katsuhiro Arai
- Center for Pediatric Inflammatory Bowel Disease, Division of Gastroenterology, National Center for Child Health and Development, Tokyo, Japan
| | - Takashi Ishige
- Department of Pediatrics, Gunma University Graduate School of Medicine, Gunma, Japan
| | - Yasushi Okazaki
- Diagnostics and Therapeutics of Intractable Diseases and Intractable Disease Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Toshiaki Shimizu
- Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
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13
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Moreels TG, Singh A. Updates on the diagnosis and management of cryptogenic multifocal ulcerative stenosing enteropathy (CMUSE) and non-steroidal enteropathy. Best Pract Res Clin Gastroenterol 2023; 64-65:101847. [PMID: 37652648 DOI: 10.1016/j.bpg.2023.101847] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Accepted: 07/02/2023] [Indexed: 09/02/2023]
Abstract
Crohn's disease and coeliac disease are well-known to induce ulcerations in the small-bowel. However, there is a group of very rare chronic ulcerative conditions of the small intestine that has emerged from the intestinal black box nearly 70 years ago, and that has gained interest with the advent of small-bowel capsule endoscopy and device-assisted enteroscopy. These distinct ulcerative enteropathies have come to our attention, and continue to reveal their aetiology and treatment options. Two distinct entities, called cryptogenic multifocal ulcerative stenosing enteritis/enteropathy (CMUSE) and chronic nonspecific multiple ulcers of the small intestine (CNSU) are gaining more clinical attention. CMUSE was first reported in Europe, whereas CNSU was exclusively diagnosed in Japanese patients. With the identification of susceptibility genes impacting prostaglandin metabolism, CMUSE and CNSU have become two distinct pathologies within the group of prostaglandin-associated enteropathies, to be differentiated from medication-induced enteropathies, especially non-steroidal anti-inflammatory drugs (NSAID)-induced enteropathy with similar intestinal ulcerations due to interference with prostaglandin metabolism. The current review provides an historical overview of CMUSE and CNSU publications, in addition to the currently available diagnostic and treatment options, and how to differentiate these rare enteropathies from NSAID-induced enteropathy.
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Affiliation(s)
- Tom G Moreels
- University Hospital Saint-Luc, Department of Gastroenterology & Hepatology, Ave Hippocrate 10, 1200, Brussels, Belgium.
| | - Ayaskanta Singh
- SUM Ultimate Medicare and SUM Hospital, Department of Gastroenterology, SOA University, Bhubaneswar, Odisha, India.
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14
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Kimura K, Jimbo K, Arai N, Sato M, Suzuki M, Kudo T, Yano T, Shimizu T. Eosinophilic enteritis requiring differentiation from chronic enteropathy associated with SLCO2A1 gene: A case report. World J Gastroenterol 2023; 29:1757-1764. [PMID: 37077520 PMCID: PMC10107214 DOI: 10.3748/wjg.v29.i11.1757] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Revised: 02/06/2023] [Accepted: 02/27/2023] [Indexed: 03/17/2023] Open
Abstract
BACKGROUND Eosinophilic gastrointestinal disease (EGID) is a disorder characterized by infiltration of eosinophils causing mucosal damage and dysfunction of the gastrointestinal tract. The endoscopic findings of eosinophilic enteritis (EoN), an EGID variant, are nonspecific and occasionally difficult to diagnose. In contrast, chronic enteropathy associated with SLCO2A1 (CEAS) is a chronic persistent small intestinal disorder characterized by endoscopic findings such as multiple oblique and circular ulcers.
CASE SUMMARY We report the case of a 10-year-old boy who had suffered abdominal pain and fatigue for the preceding 6 mo. He was referred to our institute for investigation of suspected gastrointestinal bleeding because of severe anemia with hypoproteinemia and positive fecal human hemoglobin. The upper and lower gastrointestinal endoscopic findings were normal; however, double-balloon small bowel endoscopy showed multiple oblique and circular ulcers with discrete margins and mild constriction of the intestinal lumen in the ileum. The findings were highly consistent with CEAS, but urine prostaglandin metabolites were within normal limits, and no previously reported mutations in the SLCO2A1 gene were identified. Histological evaluation demonstrated moderate to severe eosinophilic infiltration localized to the small intestine suggesting a diagnosis of EoN. Clinical remission was maintained with montelukast and a partial elemental diet, but emergent surgery for bowel obstruction due to small intestinal stenosis was performed two years after the initial treatment.
CONCLUSION EoN should be considered in the differential diagnosis of CEAS-like small intestinal ulcerative lesions and normal urinary prostaglandin metabolite levels.
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Affiliation(s)
- Kantaro Kimura
- Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo 113-8421, Japan
| | - Keisuke Jimbo
- Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo 113-8421, Japan
| | - Nobuyasu Arai
- Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo 113-8421, Japan
| | - Masamichi Sato
- Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo 113-8421, Japan
| | - Mitsuyoshi Suzuki
- Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo 113-8421, Japan
| | - Takahiro Kudo
- Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo 113-8421, Japan
| | - Tomonori Yano
- Department of Medicine, Jichi Medical University, Tochigi 329-0498, Japan
| | - Toshiaki Shimizu
- Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo 113-8421, Japan
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15
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Jeong B, Park SH, Ye BD, Kim J, Yang SK. A Novel Chronic Enteropathy Associated with SLCO2A1 Gene Mutation: Enterography Findings in a Multicenter Korean Registry. Korean J Radiol 2023; 24:305-312. [PMID: 36907595 PMCID: PMC10067698 DOI: 10.3348/kjr.2022.0684] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Revised: 01/19/2023] [Accepted: 01/19/2023] [Indexed: 03/14/2023] Open
Abstract
OBJECTIVE Chronic enteropathy associated with SLCO2A1 gene (CEAS) is a recently recognized disease. We aimed to evaluate the enterographic findings of CEAS. MATERIALS AND METHODS Altogether, 14 patients with CEAS were confirmed based on known SLCO2A1 mutations. They were registered in a multicenter Korean registry between July 2018 and July 2021. Nine of the patients (37.2 ± 13 years; all female) who underwent surgery-naïve-state computed tomography enterography (CTE) or magnetic resonance enterography (MRE) were identified. Two experienced radiologists reviewed 25 and 2 sets of CTE and MRE examinations, respectively, regarding the small bowel findings. RESULTS In initial evaluation, eight patients showed a total of 37 areas with mural abnormalities in the ileum on CTE, including 1-4 segments in six and > 10 segments in two patients. One patient showed unremarkable CTE. The involved segments were 10-85 mm (median, 20 mm) in length, 3-14 mm (median, 7 mm) in mural thickness, circumferential in 86.5% (32/37), and showed stratified enhancement in the enteric and portal phases in 91.9% (34/37) and 81.8% (9/11), respectively. Perienteric infiltration and prominent vasa recta were noted in 2.7% (1/37) and 13.5% (5/37), respectively. Bowel strictures were identified in six patients (66.7%), with a maximum upstream diameter of 31-48 mm. Two patients underwent surgery for strictures immediately after the initial enterography. Follow-up CTE and MRE in the remaining patients showed minimal-to-mild changes in the extent and thickness of the mural involvement for 17-138 months (median, 47.5 months) after initial enterography. Two patients required surgery for bowel stricture at 19 and 38 months of follow-up, respectively. CONCLUSION CEAS of the small bowel typically manifested on enterography in varying numbers and lengths of abnormal ileal segments that showed circumferential mural thickening with layered enhancement without perienteric abnormalities. The lesions caused bowel strictures that required surgery in some patients.
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Affiliation(s)
- Boryeong Jeong
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Seong Ho Park
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.,Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
| | - Byong Duk Ye
- Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.,Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.,Digestive Diseases Research Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jihun Kim
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Suk-Kyun Yang
- Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.,Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.,Digestive Diseases Research Center, University of Ulsan College of Medicine, Seoul, Korea
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16
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Raynor A, Stefanescu C, Bruneel A, Puy H, Peoc’h K, Manceau H. Reversible atransferrinemia in a patient with chronic enteropathy: is transferrin mandatory for iron transport? Biochem Med (Zagreb) 2023; 33:010801. [PMID: 36627980 PMCID: PMC9807235 DOI: 10.11613/bm.2023.010801] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Accepted: 09/05/2022] [Indexed: 12/23/2022] Open
Abstract
Herein, we report the case of a 42-year-old woman, hospitalized in a French tertiary hospital for a relapse of a chronic enteropathy, who was found on admission to have no detectable serum transferrin. Surprisingly, she only exhibited mild anaemia. This atransferrinemia persisted for two months throughout her hospitalization, during which her haemoglobin concentration remained broadly stable. Based on her clinical history and evolution, we concluded to an acquired atransferrinemia secondary to chronic undernutrition, inflammation and liver failure. We discuss the investigations performed in this patient, and hypotheses regarding the relative stability of her haemoglobin concentration despite the absence of detectable transferrin.
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Affiliation(s)
- Alexandre Raynor
- Department of Biochemistry, Bichat University Hospital, APHP.Nord, Paris, France
| | - Carmen Stefanescu
- Department of Gastroenterology, Beaujon University Hospital, APHP. Nord, Clichy, France
| | - Arnaud Bruneel
- Department of Biochemistry, Bichat University Hospital, APHP.Nord, Paris, France
| | - Hervé Puy
- Department of Biochemistry, Bichat University Hospital, APHP.Nord, Paris, France,French Porphyria Center, Louis Mourier University Hospital, Colombes, France,Université Paris Cité, INSERM U1149, HIROS Heme Iron and Oxidative Stress, Inflammation Research Center, Paris, France
| | - Katell Peoc’h
- Department of Biochemistry, Bichat University Hospital, APHP.Nord, Paris, France,Department of Biochemistry, Beaujon University Hospital, APHP. Nord, Clichy, France,Université Paris Cité, INSERM U1149, HIROS Heme Iron and Oxidative Stress, Inflammation Research Center, Paris, France
| | - Hana Manceau
- Department of Biochemistry, Beaujon University Hospital, APHP. Nord, Clichy, France,Université Paris Cité, INSERM U1149, HIROS Heme Iron and Oxidative Stress, Inflammation Research Center, Paris, France,Corresponding author:
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17
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Hamon A, Cazals-Hatem D, Stefanescu C, Uzzan M, Treton X, Sauvanet A, Panis Y, Monsinjon M, Bonvalet F, Corcos O, Azouguene E, Cerf-Bensussan N, Bouhnik Y, Charbit-Henrion F. Crohn-like disease affecting small bowel due to monogenic SLCO2A1 mutations: First cases of Chronic Enteropathy Associated with SLCO2A1 gene (CEAS) in France. J Crohns Colitis 2022; 17:816-820. [PMID: 36480694 PMCID: PMC10155746 DOI: 10.1093/ecco-jcc/jjac181] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Multiple chronic ulcers of small intestine are mainly ascribed to Crohn's disease. Among possible differential diagnoses are chronic ulcers of small bowel caused by abnormal activation of the prostaglandin pathway either in the archetypal but uncommon non-steroidal anti-inflammatory drug (NSAID)-induced enteropathy, or in rare monogenic disorders due to PLA2G4A and SLCO2A1 mutations. SLCO2A1 variants are responsible for CEAS (Chronic enteropathy associated with SLCO2A1), a syndrome which was exclusively reported in patients of Asian origin. Herein, we report the case of two French female siblings with CEAS. CASE REPORT P1 underwent iterative bowel resections (removing 1 meter of small bowel in total) for recurrent strictures and perforations. Her sister P2 had a tight duodenal stricture which required partial duodenectomy. Next-generation sequencing was performed on P1's DNA and identified 2 compound heterozygous variants in exon 12 in SLCO2A1, which were also present in P2. CONCLUSION CEAS can be detected within the European population and raise the question of its incidence and recognition outside Asia. Presence of intractable recurrent ulcerations of the small intestine mimicking Crohn's disease with concentric stricture should motivate a genetic search for SLCO2A1 mutations, particularly in the context of family history or consanguinity.
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Affiliation(s)
- Annick Hamon
- Department of Gastroenterology, Beaujon Hospital, Assistance Publique - Hôpitaux de Paris-Cité, University of Paris, Paris, France
| | - Dominique Cazals-Hatem
- Department of Pathology, Beaujon Hospital, Assistance Publique - Hôpitaux de Paris-Cité, University of Paris, Paris, France
| | - Carmen Stefanescu
- Department of Gastroenterology, Beaujon Hospital, Assistance Publique - Hôpitaux de Paris-Cité, University of Paris, Paris, France.,Groupe hospitalier Ambroise Paré - Hartmann, Institut des MICI, Neuilly sur Seine, France
| | - Mathieu Uzzan
- Department of Gastroenterology, Mondor Hospital, Assistance Publique - Hôpitaux de Paris-Cité, University of Paris, Paris, France
| | - Xavier Treton
- Department of Gastroenterology, Beaujon Hospital, Assistance Publique - Hôpitaux de Paris-Cité, University of Paris, Paris, France.,Groupe hospitalier Ambroise Paré - Hartmann, Institut des MICI, Neuilly sur Seine, France
| | - Alain Sauvanet
- Department of Hepato-biliary Surgery, Beaujon Hospital, Assistance Publique - Hôpitaux de Paris-Cité, University of Paris, Paris, France
| | - Yves Panis
- Department of Hepato-biliary Surgery, Beaujon Hospital, Assistance Publique - Hôpitaux de Paris-Cité, University of Paris, Paris, France
| | - Marie Monsinjon
- Department of Colorectal Surgery, Beaujon Hospital, Assistance Publique - Hôpitaux de Paris-Cité, University of Paris, Paris, France
| | - Fanny Bonvalet
- Department of Radiology, Beaujon Hospital, Assistance Publique - Hôpitaux de Paris-Cité, University of Paris, Paris, France
| | - Olivier Corcos
- Department of Gastroenterology, Beaujon Hospital, Assistance Publique - Hôpitaux de Paris-Cité, University of Paris, Paris, France
| | - Emilie Azouguene
- Department of Genomic Medecine for Rare Diseases, Necker-Enfants Malades Hospital, Assistance Publique - Hôpitaux de Paris, University of Paris-Cité, Paris, France
| | | | - Yoram Bouhnik
- Department of Gastroenterology, Beaujon Hospital, Assistance Publique - Hôpitaux de Paris-Cité, University of Paris, Paris, France.,Groupe hospitalier Ambroise Paré - Hartmann, Institut des MICI, Neuilly sur Seine, France
| | - Fabienne Charbit-Henrion
- Department of Genomic Medecine for Rare Diseases, Necker-Enfants Malades Hospital, Assistance Publique - Hôpitaux de Paris, University of Paris-Cité, Paris, France.,INSERM UMR1163, Intestinal Immunity, Institut Imagine, Paris, France
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18
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Dönger U, Warasnhe K, Özçay F, Şule Haskoloğlu Z, İbrahim Aydın H, Ceylaner S. Chronic enteropathy associated with SLCO2A1 gene and hereditary fructose intolerance: A coincidence of two rare diseases. Arab J Gastroenterol 2022; 23:290-293. [PMID: 36384942 DOI: 10.1016/j.ajg.2022.10.007] [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: 05/23/2022] [Revised: 08/08/2022] [Accepted: 10/16/2022] [Indexed: 11/14/2022]
Abstract
Chronic enteropathy associated with SLCO2A1 gene (CEAS) is a rare disorder characterized by multiple small intestine ulcers. Patients with CEAS typically present with chronic anemia and gastrointestinal bleeding. Besides CEAS, SLCO2A1 mutations cause primary hypertrophic osteoarthropathy (PHO) which is considered as an extraintestinal manifestation in CEAS patients. Since CEAS and Crohn's disease are clinically indistinguishable, patients are often misdiagnosed with Crohn's disease. Herein, we describe a 4-year-old Turkish girl with CEAS due to homozygous pathogenic variant (c.656C > T) in SLCO2A1 with concomitant hereditary fructose intolerance (HFI) caused by homozygous pathogenic variant (c.1005C > G) in ALDOB. Prompt restriction of fructose, sucrose and sorbitol resulted in hepatomegaly regression and mild amelioration of patient's symptoms. Despite budesonide and azathioprine treatments, patient's protein losing enteropathy and chronic anemia did not improve. Although previous CEAS cases were reported from East Asian countries, it is likely to occur in people from other geographic areas. CEAS seems to be underdiagnosed and high index of suspicion is required for the diagnosis of this rare entity. Patients with prior diagnosis of Crohn's disease with no response to immunosuppressive treatment or anti-TNF therapy should be re-evaluated for possible CEAS diagnosis.
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Affiliation(s)
- Utku Dönger
- Department of Pediatrics, Başkent University Faculty of Medicine, Ankara, Turkey
| | - Khaled Warasnhe
- Department of Pediatrics, Başkent University Faculty of Medicine, Ankara, Turkey.
| | - Figen Özçay
- Department of Pediatric Gastroenterology and Hepatology, Başkent University Faculty of Medicine, Ankara, Turkey
| | - Zehra Şule Haskoloğlu
- Department of Pediatric Immunology and Allergy, Ankara University Faculty of Medicine, Ankara, Turkey
| | - Halil İbrahim Aydın
- Department of Metabolic Diseases, Başkent University Faculty of Medicine, Ankara, Turkey
| | - Serdar Ceylaner
- INTERGEN Genetics and Rare Diseases Diagnosis Research & Application Center, Ankara, Turkey
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19
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Long B, Tang H, Zhao X, He T, Tang M, Wan P. Chronic enteropathy associated with SLCO2A1-associated primary hypertrophic osteoarthropathy in a female patient. Clin Res Hepatol Gastroenterol 2022; 46:102021. [PMID: 36089247 DOI: 10.1016/j.clinre.2022.102021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Revised: 05/08/2022] [Accepted: 05/09/2022] [Indexed: 02/04/2023]
Affiliation(s)
- Bangce Long
- Medical Faculty of Kunming University of Science and Technology, affiliated with The First People's Hospital of Yunnan Province, Kunming, Yunnan, China; Department of Gastroenterology, the First People's Hospital of Yunnan Province, Kunming, Yunnan, China
| | - Hui Tang
- Medical Faculty of Kunming University of Science and Technology, affiliated with The First People's Hospital of Yunnan Province, Kunming, Yunnan, China; Department of Gastroenterology, the First People's Hospital of Yunnan Province, Kunming, Yunnan, China
| | - Xueru Zhao
- Medical Faculty of Kunming University of Science and Technology, affiliated with The First People's Hospital of Yunnan Province, Kunming, Yunnan, China; Department of Gastroenterology, the First People's Hospital of Yunnan Province, Kunming, Yunnan, China
| | - Tian He
- Medical Faculty of Kunming University of Science and Technology, affiliated with The First People's Hospital of Yunnan Province, Kunming, Yunnan, China; Department of Gastroenterology, the First People's Hospital of Yunnan Province, Kunming, Yunnan, China
| | - Ming Tang
- Medical Faculty of Kunming University of Science and Technology, affiliated with The First People's Hospital of Yunnan Province, Kunming, Yunnan, China; Department of Pathology, the First People's Hospital of Yunnan Province, Kunming, Yunnan, China
| | - Ping Wan
- Medical Faculty of Kunming University of Science and Technology, affiliated with The First People's Hospital of Yunnan Province, Kunming, Yunnan, China; Department of Gastroenterology, the First People's Hospital of Yunnan Province, Kunming, Yunnan, China.
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20
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Seki S, Tanaka G, Kimura T, Hayashida M, Miyoshi J, Matsuura M, Sakurai H, Hisamatsu T. Functional analysis of mutant SLCO2A1 transporters found in patients with chronic enteropathy associated with SLCO2A1. J Gastroenterol Hepatol 2022; 37:1776-1784. [PMID: 35877192 DOI: 10.1111/jgh.15968] [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: 10/20/2021] [Revised: 07/01/2022] [Accepted: 07/19/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND AND AIM Chronic enteropathy associated with the solute carrier organic anion transporter family member 2A1 (SLCO2A1), or CEAS, causes anemia and hypoalbuminemia in young people. Dysfunction of the SLCO2A1 transporter protein is thought to involve genetic mutation, but mutant proteins have not been functionally characterized. We examined the prostaglandin E2 (PGE2 ) transport ability of recombinant SLCO2A1 proteins containing 11 SLCO2A1 mutations found in CEAS patients. METHODS Wild-type and mutant SLCO2A1 proteins were forcibly expressed in Xenopus laevis oocytes, and measurements of PGE2 uptake and transport capacity were compared. The membrane protein topology and functionality of the eight SLCO2A1 mutations involving single-nucleotide substitutions were predicted using computer analysis. RESULTS The extent of functional disruption of the 11 SLCO2A1 mutations identified in CEAS patients was variable, with 10 mutations (421GT, 547GA, 664GA, 770GA, 830dupT, 830delT, 940 + 1GA, 1372GT, 1647GT, and 1807CT) resulting in loss or reduction of PGE2 transport, excluding 97GC. CONCLUSION PGE2 transport ability of recombinant SLCO2A1 in X. laevis oocytes was hindered in 10/11 SLCO2A1 mutations identified in patients with CEAS. Further studies on the relationships between the different mutations and PGE2 transport and clinical features, such as severity, are needed.
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Affiliation(s)
- Satowa Seki
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Tokyo, Japan
| | - Gen Tanaka
- Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo, Japan
| | - Toru Kimura
- Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo, Japan
| | - Mari Hayashida
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Tokyo, Japan
| | - Jun Miyoshi
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Tokyo, Japan
| | - Minoru Matsuura
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Tokyo, Japan
| | - Hiroyuki Sakurai
- Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo, Japan
| | - Tadakazu Hisamatsu
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Tokyo, Japan
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21
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Ariake C, Hosoe N, Sakurai H, Tojo A, Hayashi Y, Jl Limpias Kamiya K, Sujino T, Takabayashi K, Kosaki K, Seki S, Hisamatsu T, Ogata H, Kanai T. Chronic Enteropathy Associated with Solute Carrier Organic Anion Transporter Family, Member 2A1 (SLCO2A1) with Positive Immunohistochemistry for SLCO2A1 Protein. Intern Med 2022; 61:2607-2611. [PMID: 35185052 PMCID: PMC9492477 DOI: 10.2169/internalmedicine.8939-21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2021] [Accepted: 01/10/2022] [Indexed: 11/06/2022] Open
Abstract
Chronic enteropathy associated with solute carrier organic anion transporter family, member 2A1 (SLCO2A1) (CEAS) is a rare autosomal recessive hereditary disease characterized by chronic persistent anemia and hypoproteinemia. Its diagnosis typically requires a genetic analysis. The efficacy of immunohistochemical staining with SLCO2A1 polyclonal antibody as a pre-diagnostic tool for CEAS has been previously reported. We herein report a patient with CEAS in whom immunohistochemical staining confirmed SLCO2A1 protein expression. The immunopositive results may have been due to nonsense-mediated RNA decay. As immunohistochemical staining of SLCO2A1 protein may show immunopositive results, a genetic analysis should also be performed when CEAS is strongly clinically suspected.
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Affiliation(s)
- Chizuru Ariake
- Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Japan
- Department of Internal Medicine, Kensei Hospital, Japan
| | - Naoki Hosoe
- Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Japan
| | - Hinako Sakurai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Japan
| | - Anna Tojo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Japan
| | - Yukie Hayashi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Japan
| | - Kenji Jl Limpias Kamiya
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Japan
| | - Tomohisa Sujino
- Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Japan
| | - Kaoru Takabayashi
- Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Japan
| | - Kenjiro Kosaki
- Center for Medical Genetics, Keio University School of Medicine, Japan
| | - Satowa Seki
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Japan
| | - Tadakazu Hisamatsu
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Japan
| | - Haruhiko Ogata
- Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Japan
| | - Takanori Kanai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Japan
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22
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McAlindon ME. Cryptogenic multifocal ulcerating stenosing enteritis and other under-recognised small bowel inflammatory enteropathies. Curr Opin Gastroenterol 2022; 38:279-284. [PMID: 35275899 DOI: 10.1097/mog.0000000000000833] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
PURPOSE OF REVIEW Capsule endoscopy and more sensitive radiological techniques have resulted in more enteropathies being detected. A rare disease of unknown aetiology, 'cryptogenic multifocal ulcerating stenosing enteritis' or 'chronic nonspecific multiple ulcers of the small intestine' (CNSU), has long been recognised. This review aims to describe how disease can be better diagnosed and differentiated from other small bowel inflammatory disorders. RECENT FINDINGS Genetic studies have shown that some patients with CNSU (the term used in Japanese studies) express SLCO2A1 gene mutations, a gene which encodes a prostaglandin transporter expressed on vascular endothelium, allowing a more specific diagnosis of 'chronic enteropathy associated with SLCO2A1'. Mutations in the PLA2G4A gene result in cytosolic phospholipase A2α deficiency and reduced arachidonic acid for prostaglandin synthesis leading to a severe ulcerating, stenosing and fistulating small bowel disease. SUMMARY A 'prostaglandin-related enteropathy' should be considered in patients with atypical small bowel ulceration and stenosis. Genetic analysis will allow the detection of SLCO2A1 and PLA2G4A gene mutations. However, a careful history of medication use and a urinary metabolite screen may reveal the use of nonsteroidal anti-inflammatory drugs, a common cause of small bowel injury which is well recognised as being mediated by prostaglandin inhibition.
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Affiliation(s)
- Mark E McAlindon
- Academic Department of Gastroenterology and Hepatology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield S10 2JF, UK
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23
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Editorial: Pathology in the small bowel - challenges, trials and tribulations. Curr Opin Gastroenterol 2022; 38:261-262. [PMID: 35645019 DOI: 10.1097/mog.0000000000000834] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
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24
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Matsuura M, Matsumoto T, Naito Y, Saitoh Y, Kanai T, Suzuki Y, Tanaka S, Ogata H, Hisamatsu T. Advanced endoscopy for the management of inflammatory digestive diseases: Review of the Japan Gastroenterological Endoscopy Society core session. Dig Endosc 2022; 34:729-735. [PMID: 35037317 DOI: 10.1111/den.14234] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Revised: 12/28/2021] [Accepted: 01/11/2022] [Indexed: 02/08/2023]
Abstract
A series of workshops entitled "Advanced endoscopy in the management of inflammatory digestive disease" was held at the 97th to 100th biannual meeting of the Japan Gastroenterological Endoscopy Society. During these core sessions, research findings concerning various endoscopic practices in the field of inflammatory bowel disease (IBD) were presented, and meaningful discussions were shared on the evolving role and future challenges of endoscopy in IBD. This article reviews these core sessions and discusses current topics on the role of endoscopy, focusing on the diagnosis, disease monitoring, mucosal healing assessments, cancer surveillance, and therapeutic interventions in IBD.
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Affiliation(s)
- Minoru Matsuura
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Tokyo, Japan
| | - Takayuki Matsumoto
- Division of Gastroenterology, Department of Medicine, Iwate Medical University, Iwate, Japan
| | - Yuji Naito
- Department of Human Immunology and Nutrition Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Yusuke Saitoh
- Digestive Disease Center, Asahikawa City Hospital, Hokkaido, Japan
| | - Takanori Kanai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokyo, Japan
| | - Yasuo Suzuki
- Department of Gastroenterology, Toho University Sakura Medical Center, Chiba, Japan
| | - Shinji Tanaka
- Endoscopy and Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Haruhiko Ogata
- Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan
| | - Tadakazu Hisamatsu
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Tokyo, Japan
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25
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Vuyyuru SK, Kedia S, Sahu P, Ahuja V. Immune-mediated inflammatory diseases of the gastrointestinal tract: Beyond Crohn's disease and ulcerative colitis. JGH Open 2022; 6:100-111. [PMID: 35155819 PMCID: PMC8829105 DOI: 10.1002/jgh3.12706] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2021] [Revised: 12/26/2021] [Accepted: 12/29/2021] [Indexed: 12/17/2022]
Abstract
Immune-mediated inflammatory diseases (IMIDs) are a diverse group of complex inflammatory diseases that result from dysregulated immune pathways and can involve any system of the human body. Inflammatory bowel disease (IBD) is one such disease involving the gastrointestinal (GI) system. With high prevalence in the West and increasing incidence in newly industrialized countries, IBD poses a significant burden on health care. IMIDs of the GI system other than IBD can have similar clinical features, causing diagnostic and therapeutic challenges. Although these disorders share a common pathophysiology, the defects can occur anywhere in the complex network of cytokines, inflammatory mediators, and innate and adaptive systems, leading to unregulated inflammation. Precise knowledge about them will help determine the possible targeted therapy. Thus, it is essential to distinguish these disorders from IBD. This review describes various IMIDs of the GI tract that mimic IBD.
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Affiliation(s)
- Sudheer K Vuyyuru
- Department of GastroenterologyAll India Institute of Medical SciencesNew DelhiIndia
| | - Saurabh Kedia
- Department of GastroenterologyAll India Institute of Medical SciencesNew DelhiIndia
| | - Pabitra Sahu
- Department of GastroenterologyAll India Institute of Medical SciencesNew DelhiIndia
| | - Vineet Ahuja
- Department of GastroenterologyAll India Institute of Medical SciencesNew DelhiIndia
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26
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Huang H, Wang X, Ou D, Liu X, Wu B, Zhou B, Wang Y, Shi X. Four Variants of SLCO2A1 Identified in Three Chinese Patients with Chronic Enteropathy Associated with the SLCO2A1 Gene. Dig Dis Sci 2021; 66:2992-3001. [PMID: 33000396 DOI: 10.1007/s10620-020-06629-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2020] [Accepted: 09/16/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Chronic enteropathy associated with the SLCO2A1 gene (CEAS) is an enteropathy characterized by multiple small intestinal ulcers of nonspecific histology, also known as chronic nonspecific multiple ulcers of the small intestine. The SLCO2A1 gene encodes a prostaglandin transporter (PGT). AIMS The aim of this study was to investigate the clinical characteristics of ten Chinese patients with intestinal ulcers of unknown origin, screen them for variants of SLCO2A1, and to investigate the expression of PGT in the small intestinal mucosa of patients with CEAS. METHODS Ten Chinese patients with intestinal ulcers of unknown origin were included in this study. Blood samples were collected for whole-exome sequencing and Sanger sequencing of candidate gene variants. Immunohistochemical staining was used to investigate the expression of PGT. RESULTS These ten patients were clinically diagnosed with intestinal ulcers of unknown origin based on criteria established according to earlier publications. Three of them were genetically diagnosed as having CEAS and four candidate variants of the SLCO2A1 gene were identified, among which c.941-1G>A, c.178G>A and c.1681C>T were detected in patients with CEAS for the first time. The terminal ileum was involved in all three patients with CEAS in our study, which was different from the results of Japanese patients. The expression of PGT in the vascular endothelial cells of the intestinal mucosa tissues of patients with CEAS was negative or intermediate. CONCLUSION We summarized the clinical data of ten Chinese patients with intestinal ulcers of unknown origin and identified three novel SLCO2A1 variants from three patients with CEAS. This study improves our understanding of CEAS and broadens the spectrum of SLCO2A1 variants known to cause CEAS.
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Affiliation(s)
- Hui Huang
- Department of Medical Genetics, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China
| | - Xuehong Wang
- Department of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China
| | - Dalian Ou
- Department of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China
| | - Xiaowei Liu
- Department of Gastroenterology, Xiangya Hospital of Central South University, Changsha, 410008, Hunan, China
| | - Boda Wu
- Department of Medical Genetics, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China
- Department of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China
| | - Bai Zhou
- Department of Medical Genetics, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China
- Department of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China
| | - Yongjun Wang
- Department of Medical Genetics, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China.
- Department of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China.
| | - Xiaoliu Shi
- Department of Medical Genetics, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China
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27
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Sun K, He Q, Zhu L, Abula G, Zhao J, Chen X. Multiple small intestinal ulcers with SLCO2A1 and PLA2G4A mutation in a Chinese patient. Dig Liver Dis 2021; 53:1062-1064. [PMID: 34052181 DOI: 10.1016/j.dld.2021.04.032] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2021] [Revised: 04/25/2021] [Accepted: 04/26/2021] [Indexed: 12/11/2022]
Affiliation(s)
- Kaidi Sun
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin 300052, China
| | - Qijin He
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin 300052, China
| | - Lanping Zhu
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin 300052, China
| | - Gulisitan Abula
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin 300052, China
| | - Jingwen Zhao
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin 300052, China.
| | - Xin Chen
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin 300052, China.
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SLCO2A1 gene is the causal gene for both primary hypertrophic osteoarthropathy and hereditary chronic enteropathy. J Orthop Translat 2021; 28:10-11. [PMID: 33575166 PMCID: PMC7844433 DOI: 10.1016/j.jot.2020.12.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Revised: 12/14/2020] [Accepted: 12/15/2020] [Indexed: 02/08/2023] Open
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29
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Oba MS, Murakami Y, Nishiwaki Y, Asakura K, Ohfuji S, Fukushima W, Nakamura Y, Suzuki Y. Estimated Prevalence of Cronkhite-Canada Syndrome, Chronic Enteropathy Associated With SLCO2A1 Gene, and Intestinal Behçet's Disease in Japan in 2017: A Nationwide Survey. J Epidemiol 2021; 31:139-144. [PMID: 32092751 PMCID: PMC7813772 DOI: 10.2188/jea.je20190349] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2019] [Accepted: 02/07/2020] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Cronkhite-Canada syndrome (CCS), chronic enteropathy associated with SLCO2A1 gene (CEAS), and intestinal Behçet's disease (BD) are classified as intractable intestinal disorders in Japan. However, the national prevalence of these diseases remains unknown. We performed a nationwide survey to estimate the patient numbers and prevalence rates of these diseases throughout Japan in 2017. METHODS We conducted a mail-based survey targeting hospitals across Japan to estimate the annual numbers of patients with CCS, CEAS, and intestinal BD in 2017. Using a stratified random sampling method, we selected 2,979 hospital departments and asked them to report the number of patients who met specific diagnostic criteria. The total number of patients for each disease was estimated by multiplying the reported numbers by the reciprocal of the sampling rate and response rate. The corresponding prevalence rates per 1,000,000 population were calculated based on the mid-year population of Japan in 2017. RESULTS The overall survey response rate was 68.1% (2,029 departments). The estimated numbers of patients with CCS, CEAS, and intestinal BD were 473 (95% confidence interval [CI], 357-589), 388 (95% CI, 289-486), and 3,139 (95% CI, 2,749-3,529), respectively; the prevalence rates per 1,000,000 population were 3.7 (male: 4.0; female: 3.5), 3.1 (male: 3.0; female: 3.1), and 24.8 (male: 24.5; female: 25.0), respectively. The male-to-female ratios were 1.10, 0.94, and 0.93 for patients with CCS, CEAS, and intestinal BD, respectively. CONCLUSIONS Estimates of the national prevalence of CCS, CEAS, and intestinal BD in Japan were generated and found to be higher than those previously reported.
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Affiliation(s)
- Mari S. Oba
- Department of Medical Statistics, Toho University, Tokyo, Japan
| | | | - Yuji Nishiwaki
- Department of Environmental and Occupational Health, Toho University, Tokyo, Japan
| | - Keiko Asakura
- Department of Environmental and Occupational Health, Toho University, Tokyo, Japan
| | - Satoko Ohfuji
- Department of Public Health, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Wakaba Fukushima
- Department of Public Health, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Yosikazu Nakamura
- Department of Public Health, Jichi Medical University, Tochigi, Japan
| | - Yasuo Suzuki
- Department of Internal Medicine, Toho University Sakura Medical Center, Chiba, Japan
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30
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Nakanishi T, Nakamura Y, Umeno J. Recent advances in studies of SLCO2A1 as a key regulator of the delivery of prostaglandins to their sites of action. Pharmacol Ther 2021; 223:107803. [PMID: 33465398 DOI: 10.1016/j.pharmthera.2021.107803] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Accepted: 12/18/2020] [Indexed: 02/08/2023]
Abstract
Solute carrier organic anion transporter family member 2A1 (SLCO2A1, also known as PGT, OATP2A1, PHOAR2, or SLC21A2) is a plasma membrane transporter consisting of 12 transmembrane domains. It is ubiquitously expressed in tissues, and mediates the membrane transport of prostaglandins (PGs, mainly PGE2, PGF2α, PGD2) and thromboxanes (e.g., TxB2). SLCO2A1-mediated transport is electrogenic and is facilitated by an outwardly directed gradient of lactate. PGs imported by SLCO2A1 are rapidly oxidized by cytoplasmic 15-hydroxyprostaglandin dehydrogenase (15-PGDH, encoded by HPGD). Accumulated evidence suggests that SLCO2A1 plays critical roles in many physiological processes in mammals, and it is considered a potential pharmacological target for diabetic foot ulcer treatment, antipyresis, and non-hormonal contraception. Furthermore, whole-exome analyses suggest that recessive inheritance of SLCO2A1 mutations is associated with two refractory diseases, primary hypertrophic osteoarthropathy (PHO) and chronic enteropathy associated with SLCO2A1 (CEAS). Intriguingly, SLCO2A1 is also a key component of the Maxi-Cl channel, which regulates fluxes of inorganic and organic anions, including ATP. Further study of the bimodal function of SLCO2A1 as a transporter and ion channel is expected to throw new light on the complex pathology of human diseases. Here, we review and summarize recent information on the molecular functions of SLCO2A1, and we discuss its pathophysiological significance.
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Affiliation(s)
- Takeo Nakanishi
- Faculty of Pharmacy, Takasaki University of Health and Welfare, Takasaki, Gunma 370-0033, Japan.
| | - Yoshinobu Nakamura
- Faculty of Pharmacy, Takasaki University of Health and Welfare, Takasaki, Gunma 370-0033, Japan
| | - Junji Umeno
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Fukuoka 812-8582, Japan
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Tsuzuki Y, Aoyagi R, Miyaguchi K, Ashitani K, Ohgo H, Yamaoka M, Ishizawa K, Kayano H, Hisamatsu T, Umeno J, Hosoe N, Matsumoto T, Nakamoto H, Imaeda H. Chronic Enteropathy Associated with SLCO2A1 with Pachydermoperiostosis. Intern Med 2020; 59:3147-3154. [PMID: 33328413 PMCID: PMC7807103 DOI: 10.2169/internalmedicine.4756-20] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2020] [Accepted: 06/07/2020] [Indexed: 01/18/2023] Open
Abstract
A 49-year-old man complained of chronic palpitation and shortness of breath, which had recently become exacerbated. A blood examination indicated severe refractory anemia and hypoproteinemia. Physical examinations revealed anemia, a systolic murmur, and spoon nails. Multiple nonspecific ileal ulcers were observed. A pathological examination indicated a small granuloma with CD68-positive histiocytes. He had a deeply wrinkled forehead, chiseled face, and clubbed fingers. Radiography revealed periostosis of the fingers and long bones in the limb. He was diagnosed with pachydermoperiostosis. SLCO2A1 demonstrated a c.1807C>T homo-mutation. He was also diagnosed with SLCO2A1-associated chronic enteropathy and thus was treated with 5-aminosalicylic acid, which temporarily improved the ileal ulcers, anemia, and hypoalbuminemia.
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Affiliation(s)
- Yoshikazu Tsuzuki
- Department of General Internal Medicine, Saitama Medical University, Japan
- Department of Gastroenterology, Saitama Medical University, Japan
| | - Ryutaro Aoyagi
- Department of General Internal Medicine, Saitama Medical University, Japan
| | - Kazuya Miyaguchi
- Department of General Internal Medicine, Saitama Medical University, Japan
| | - Keigo Ashitani
- Department of General Internal Medicine, Saitama Medical University, Japan
| | - Hideki Ohgo
- Department of General Internal Medicine, Saitama Medical University, Japan
- Department of Gastroenterology, Saitama Medical University, Japan
| | - Minoru Yamaoka
- Department of General Internal Medicine, Saitama Medical University, Japan
| | | | | | - Tadakazu Hisamatsu
- The Third Department of Internal Medicine, Kyorin University School of Medicine, Japan
| | - Junji Umeno
- Department of Medicine and Clinical Science, Graduate School of Medical Science, Kyushu University, Japan
| | - Naoki Hosoe
- Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Japan
| | - Takayuki Matsumoto
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Japan
| | - Hidetomo Nakamoto
- Department of General Internal Medicine, Saitama Medical University, Japan
| | - Hiroyuki Imaeda
- Department of General Internal Medicine, Saitama Medical University, Japan
- Department of Gastroenterology, Saitama Medical University, Japan
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A novel mutation in the SLCO2A1 gene, encoding a prostaglandin transporter, induces chronic enteropathy. PLoS One 2020; 15:e0241869. [PMID: 33166338 PMCID: PMC7652309 DOI: 10.1371/journal.pone.0241869] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Accepted: 10/22/2020] [Indexed: 02/06/2023] Open
Abstract
Chronic enteropathy associated with SLCO2A1 gene (CEAS) is caused by loss-of-function mutations in SLCO2A1, which encodes a prostaglandin (PG) transporter. In this study, we report a sibling case of CEAS with a novel pathogenic variant of the SLCO2A1 gene. Compound heterozygous variants in SLCO2A1 were identified in an 8-year-old boy and 12-year-old girl, and multiple chronic nonspecific ulcers were observed in the patients using capsule endoscopy. The splice site mutation (c.940 + 1G>A) of the paternal allele was previously reported to be pathogenic, whereas the missense variant (c.1688T>C) of the maternal allele was novel and had not yet been reported. The affected residue (p.Leu563Pro) is located in the 11th transmembrane domain (helix 11) of SLCO2A1. Because SLCO2A1 mediates the uptake and clearance of PGs, the urinary PG metabolites were measured by liquid chromatography coupled to tandem mass spectrometry. The urinary tetranor-prostaglandin E metabolite levels in the patients were significantly higher than those in unaffected individuals. We established cell lines with doxycycline-inducible expression of wild type SLCO2A1 (WT-SLCO2A1) and the L563P mutant. Immunofluorescence staining showed that WT-SLCO2A1 and the L563P mutant were dominantly expressed on the plasma membranes of these cells. Cells expressing WT-SLCO2A1 exhibited time- and dose-dependent uptake of PGE2, while the mutant did not show any uptake activity. Residue L563 is very close to the putative substrate-binding site in SLCO2A1, R561 in helix 11. However, in a molecular model of SLCO2A1, the side chain of L563 projected outside of helix 11, indicating that L563 is likely not directly involved in substrate binding. Instead, the substitution of Pro may twist the helix and impair the transporter function. In summary, we identified a novel pathogenic variant of SLCO2A1 that caused loss-of-function and induced CEAS.
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33
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Fang Y, Gu W, Luo Y, Chen J. Obscure gastrointestinal bleeding caused by congenital enteropathy in a Chinese young child-a case report. BMC Pediatr 2020; 20:438. [PMID: 32943023 PMCID: PMC7500552 DOI: 10.1186/s12887-020-02333-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Accepted: 09/08/2020] [Indexed: 11/30/2022] Open
Abstract
Background SLCO2A1 was recently reported to cause nonspecific ulcers at small bowel, it was named as chronic enteropathy associated with SLCO2A1 (CEAS). It was rarely reported beyond the Japanese population. Case presentation A 4-year-5-month old girl presented with intractable anemia since 1-year-3-month. Her stool occult blood test was positive and the result of esophagogastroduodenoscopy and colonoscopy were normal. She was considered as obscure gastrointestinal bleeding. The magnetic resonance enterography and ultrasound of small intestinal revealed segmental thickening of small bowel. The capsule endoscopy detected ulcers, erosion and slightly stenosis near the site of junction of jejunum and ileum. She was considered chronic non-specific multiple ulcers of the small intestine and was advised to have whole exon sequencing. She was treated with exclusive enteral nutrition and iron supplement for two months. However, she was not responsive to this treatment, then she had three doses of infliximab. At the same time, the next-generation sequencing of this patient revealed two novel compound heterozygous mutations in SLCO2A1. She was diagnosed with CEAS and was treated with oral mercaptopurine. Her hemoglobin level was stable and the serum albumin level was slightly decreased during the follow up. Conclusion CEAS may present as nonspecific small bowel ulcers, and misinterpret as small bowel Crohn’s disease. Genetic tests may help with the precise diagnosis of small bowel ulcers.
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Affiliation(s)
- Youhong Fang
- Department of Gastroenterology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 3333 Bin Sheng RoadZhejiang Province, Hangzhou, 310052, China
| | - Weizhong Gu
- Department of Pathology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Youyou Luo
- Department of Gastroenterology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 3333 Bin Sheng RoadZhejiang Province, Hangzhou, 310052, China
| | - Jie Chen
- Department of Gastroenterology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 3333 Bin Sheng RoadZhejiang Province, Hangzhou, 310052, China.
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Kashiwagi K, Jimbo K, Hosoi K, Miyano G, Kudo T, Yamataka A, Shimizu T. A novel segmental absence of intestinal musculature with small intestinal stenosis: a case report. BMC Gastroenterol 2020; 20:272. [PMID: 32807081 PMCID: PMC7433357 DOI: 10.1186/s12876-020-01419-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2020] [Accepted: 08/10/2020] [Indexed: 02/01/2023] Open
Abstract
Background Segmental absence of intestinal musculature (SAIM) is a rare cause of intestinal obstruction and perforation due to partial or complete defects in the intestinal muscularis propria in neonates and is occasionally observed in adulthood. Case presentation The first case of small intestinal stenosis derived from SAIM, which was difficult to differentiate from Crohn’s disease (CD), is reported. A 4-year-old girl presented with abdominal pain, anemia, and a positive fecal occult blood test. She was initially diagnosed with CD and started on treatment. Because her gastrointestinal symptoms persisted, her previous pediatricians tried to carry out capsule endoscopy, but it was not possible because the patency capsule was retained. Therefore, she was referred to our institute and re-evaluated. The patency capsule examination was repeated to re-evaluate small intestinal passage, but it stagnated again. Abdominal ultrasonography showed a poorly deformable intestinal tract that narrowed rapidly from the dilated segment and had a thin wall with an irregular laminar structure. In addition, unlike the typical ultrasonic CD findings, the power Doppler signal enhancement at the intestinal wall and “creeping fat sign” were not found. The patient was referred for laparoscopic observation to pediatric surgeons, who confirmed a prominently dilated intestinal tract 40 cm proximal to the ileocecal valve, which was resected. Histopathological findings showed longitudinal muscle hypoplasia of the resected, dilated intestinal tract and fat replacement of the muscle layer. At the stenosis site, the muscle layer was fibrotic and showed incomplete muscle arrangement. Because of these findings, she was diagnosed with SAIM. After the surgical treatment, no gastrointestinal symptoms relapsed, and the fecal occult blood test has remained negative for 2 years. Moreover, 8 months after surgery, double-balloon endoscopy showed no abnormalities, such as a longitudinal ulcer and cobblestone appearance. Conclusions In the present case, SAIM involved not only intestinal ileus and perforation, but also small intestinal stenosis. Although no other reports have demonstrated the usefulness of abdominal ultrasonography for the diagnosis of SAIM, the present report suggests that ultrasonography may be useful for differentiating SAIM from CD by close observation of the area around the small intestinal stenosis.
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Affiliation(s)
- Kosuke Kashiwagi
- Department of Pediatrics, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Keisuke Jimbo
- Department of Pediatrics, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
| | - Kenji Hosoi
- Department of Pediatrics, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Go Miyano
- Department of Pediatric General and Urobenital Surgery, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Takahiro Kudo
- Department of Pediatrics, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Atsuyuki Yamataka
- Department of Pediatric General and Urobenital Surgery, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Toshiaki Shimizu
- Department of Pediatrics, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
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Chen D, Liu W, Zhou W, Zheng W, Wu D, Qian J. Retrospective study of the differential diagnosis between cryptogenic multifocal ulcerous stenosing enteritis and small bowel Crohn's disease. BMC Gastroenterol 2020; 20:252. [PMID: 32758146 PMCID: PMC7409495 DOI: 10.1186/s12876-020-01389-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2020] [Accepted: 07/16/2020] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Being a rare disease, cryptogenic multifocal ulcerous stenosing enteritis (CMUSE) is easily misdiagnosed as small bowel Crohn's disease (SBCD). AIMS This study was aimed to compare clinical features of CMUSE to SBCD. METHODS Fourteen patients with CMUSE and 61 patients with SBCD were retrospectively analyzed. RESULTS Hematochezia was more frequent in CMUSE patients (10, 71.4% vs 23, 37.7%, P = 0.022), while diarrhea was more common in SBCD patients (23, 37.7% vs 0, 0.0%, P = 0.015). More patients with CMUSE developed intestinal stenosis than with SBCD (14, 100% vs 37, 60.7%, P = 0.011). 30 (50.0%) SBCD patients and none CMUSE patients had an elevated erythrocyte sedimentation rate level (P = 0.001). Extra-enteric findings found by computed tomography enterography were significantly more prevalent in SBCD patients than in CMUSE patients (25,71.4% vs 3,25%, P = 0.013). Longitudinal ulcers found by endoscopy were more common in SBCD patients (16, 37.2% vs 0, 0.0%, P = 0.041), while circumferential ulcers were more common in CMUSE patients (6, 54.6% vs 8, 18.6%, P = 0.041). All ulcers observed in CMUSE patients were within mucosal and submucosal layers, but 8 (44.4%) SBCD patients had deep ulcers that reached beyond submucosal layers (P = 0.003). Ulcers were located at strictures in 9 (90.0%) CMUSE patients but only in 1 (5.6%) SBCD patient (P = 0.000). CONCLUSIONS Gastrointestinal symptoms, erythrocyte sedimentation rate levels, radiologic, endoscopic and pathologic features help to distinguish CMUSE from SBCD.
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Affiliation(s)
- Dan Chen
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shuaifuyuan, No.1, Dongcheng District, Beijing, 100730, China
| | - Wei Liu
- Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Weixun Zhou
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Weiyang Zheng
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shuaifuyuan, No.1, Dongcheng District, Beijing, 100730, China
| | - Dong Wu
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shuaifuyuan, No.1, Dongcheng District, Beijing, 100730, China.
| | - Jiaming Qian
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shuaifuyuan, No.1, Dongcheng District, Beijing, 100730, China.
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Sonoda A, Wada Y, Togo K, Mizukami K, Fuyuno Y, Umeno J, Fujioka S, Fukuda K, Okamoto K, Ogawa R, Okimoto T, Murakami K. Characteristic Facial Appearance Was the Key to Diagnosing Chronic Enteropathy Associated with SLCO2A1-associated Primary Hypertrophic Osteoarthropathy. Intern Med 2020; 59:491-494. [PMID: 31611528 PMCID: PMC7056367 DOI: 10.2169/internalmedicine.3369-19] [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] [Indexed: 12/12/2022] Open
Abstract
Patients with chronic enteropathy associated with SLCO2A1 (CEAS) develop multiple circular, longitudinal, or eccentric ulcers in the ileum. It is sometimes difficult to distinguish CEAS from Crohn's disease. CEAS and primary hypertrophic osteoarthropathy (PHO) are together known to be caused by a mutation of SLCO2A1 gene. The case of a 65-year-old man whose characteristic appearance due to pachydermia of the forehead folds led to the diagnosis of CEAS with PHO is presented.
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Affiliation(s)
- Akira Sonoda
- Department of Gastroenterology, Oita University, Japan
| | - Yasuhiro Wada
- Department of Gastroenterology, Oita University, Japan
- Division of Diagnostic Pathology, Department of Clinical Laboratory Medicine, Shiga University of Medical Science, Japan
| | - Kazumi Togo
- Department of Gastroenterology, Oita University, Japan
| | | | - Yuta Fuyuno
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Japan
| | - Junji Umeno
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Japan
| | - Shin Fujioka
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Japan
| | | | | | - Ryo Ogawa
- Department of Gastroenterology, Oita University, Japan
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Wang Q, Li YH, Lin GL, Li Y, Zhou WX, Qian JM, Xia WB, Wu D. Primary hypertrophic osteoarthropathy related gastrointestinal complication has distinctive clinical and pathological characteristics: two cases report and review of the literature. Orphanet J Rare Dis 2019; 14:297. [PMID: 31878983 PMCID: PMC6933916 DOI: 10.1186/s13023-019-1264-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2018] [Accepted: 11/22/2019] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Primary hypertrophic osteoarthropathy (PHO) is a rare disease related to HPGD and SLCO2A1 gene mutation. Gastrointestinal involvement of PHO is even rarer with unknown pathogenesis. Clinical features of GI complication in PHO mimics other auto-immune based bowel entities, such as inflammatory bowel diseases and cryptogenic multifocal ulcerous stenosing enteritis (CMUSE). We aimed to analyze the clinical, genetic, radiological and pathological features of Chinese patients with PHO and determine the difference between PHO patients presenting with and without GI involvement. METHODS We reported two PHO cases with gastrointestinal involvement and reviewed all the studies of PHO in Chinese population published from January 1, 2000, to April 30, 2018. Clinical and genetic presentations of PHO in Chinese patients were analyzed. We compared the characteristics of those patients with gastrointestinal involvement against those without. RESULTS The two patients were both males with complete-form PHO for more than 10 years. GI related symptoms included diarrhea, chronic gastrointestinal hemorrhage, incomplete intestinal obstruction, anemia, and edema, which were unresponsive to etoricoxib treatment. Radiological examinations revealed segmental intestinal stenosis and thickened intestinal wall. Endoscopic findings included multiple ulcers and mucosal inflammation. Both patients had mutations of SLCO2A1 according to sequence analysis. The surgical pathology revealed chronic inflammation involving the intestinal mucosa and submucosa, similar to histological changes in CMUSE. According to the systemic review of 158 Chinese patients with PHO, 17.2% had gastrointestinal involvement, including peptic ulcer, gastric polyps, hypertrophic gastritis, and segmental intestinal stenosis. Patients with gastrointestinal involvement were more likely to have anemia (40.0% vs. 4.5%, P < 0.001), hypoalbuminemia (16.7% vs. 0.9%, P = 0.003), and myelofibrosis (19.0% vs. 0.9%, P = 0.002) than those without. Most patients with gastrointestinal complication had SLCO2A1 mutation (86.7%, 13 /15). CONCLUSIONS Digestive tract involvement is uncommon in patients with PHO and often presents with anemia, and hypoalbuminemia resulted from intestinal inflammation. The intestinal pathologic characteristics are distinct from Crohn's disease but similar to CMUSE. Mutations in SLCO2A1 might be the pathogenic cause of GI involvement of PHO. NSAIDs may not be effective for PHO patients with gastrointestinal complications.
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Affiliation(s)
- Qiang Wang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Ying-he Li
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Guo-le Lin
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Yue Li
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Wei-xun Zhou
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Jia-ming Qian
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Wei-bo Xia
- Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Dong Wu
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
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Hu P, He H, Dai N, Zhang S, Deng L. Chronic enteropathy associated with SLCO2A1 gene: A case report and literature review. Clin Res Hepatol Gastroenterol 2019; 43:e68-e72. [PMID: 31196708 DOI: 10.1016/j.clinre.2019.05.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2019] [Revised: 05/05/2019] [Accepted: 05/07/2019] [Indexed: 02/04/2023]
Abstract
A case of chronic enteropathy associated with SLCO2A1 gene (CEAS) is presented. The female patient was readmitted four times during a three-year follow-up period for intractable dropsy and anemia. Multiple ulcers of small bowel wall were revealed by endoscopic examination. Computed tomography enterography (CTE) and magnetic resonance enterography (MRE) showed the segmental wall thickening of the small bowel. Hepatosplenomegaly and increased bone density of spine and pelvis suggested the diagnosis of myelofibrosis. X-ray films showed the cortical thickening of tibiofibula. The mutations of SLCO2A1 gene were revealed by gene test and the diagnosis of CEAS was confirmed. According to our case report, imaging examinations, including CTE, MRE and X-ray films provide additional valuable information during the diagnostic procedure of CEAS.
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Affiliation(s)
- Peng Hu
- Department of Radiology, Zhejiang University School of Medicine, Sir Run Run Shaw hospital, 3 East Qingchun Road, 310016 Hangzhou City, Zhejiang Province, China
| | - Huiqin He
- Department of Gastroenterology, Zhejiang University School of Medicine, Sir Run Run Shaw hospital, 310016 Hangzhou City, Zhejiang Province, China
| | - Ning Dai
- Department of Gastroenterology, Zhejiang University School of Medicine, Sir Run Run Shaw hospital, 310016 Hangzhou City, Zhejiang Province, China
| | - Shizheng Zhang
- Department of Radiology, Zhejiang University School of Medicine, Sir Run Run Shaw hospital, 3 East Qingchun Road, 310016 Hangzhou City, Zhejiang Province, China
| | - Liping Deng
- Department of Radiology, Zhejiang University School of Medicine, Sir Run Run Shaw hospital, 3 East Qingchun Road, 310016 Hangzhou City, Zhejiang Province, China.
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Singh A. Cryptogenic Multifocal Ulcerating Stenosing Enteropathy(CMUSE) and/or Chronic Non-specific Multiple Ulcers of the Small Intestine(CNSU) and Non-granulomatous Ulcerating Jejunoileitis (NGUJI). Curr Gastroenterol Rep 2019; 21:53. [PMID: 31501950 DOI: 10.1007/s11894-019-0721-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
PURPOSE OF REVIEW The purpose is to make aware of the existence of the rare and exclusive small intestine (SI) diseases, namely cryptogenic multifocal ulcerating stenosing enteropathy (CMUSE) or chronic non-specific multiple ulcers of the small intestine (CNSU) and non-granulomatous ulcerating jejunoileitis (NGUJI). The article will elucidate their epidemiology, pathogenesis, clinical features, diagnosis, differentiating features and management. RECENT FINDINGS Recent papers have published the clinical features and diagnostic criteria of CMUSE/CNSU and NGUJI. CNSU/CMUSE is caused by gene mutations involved in the prostaglandin pathways. Although capsule endoscopy can detect these lesions, it carries a risk of retention. TNF antagonists and azathioprine have shown response in few cases. CMUSE/CNSU and NGUJI are uncommon diseases that cause relapsing SI obstruction and bleed due to short-segment strictures and multiple shallow ulcers. This article focuses on current knowledge and novel insights regarding their pathogenesis, genetics, clinical features, diagnostic criteria and management. Multicentric clinical and genetic studies are the need of the hour.
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Affiliation(s)
- Ayaskanta Singh
- Department of Gastroenterology and Hepatobiliary Sciences, IMS and SUM Hospital, Siksha 'O' Anusandhan, deemed to be University, Kalinga Nagar, Bhubaneswar, Orissa, 751003, India.
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Matsuno Y, Umeno J, Esaki M, Hirakawa Y, Fuyuno Y, Okamoto Y, Hirano A, Yasukawa S, Hirai F, Matsui T, Hosomi S, Watanabe K, Hosoe N, Ogata H, Hisamatsu T, Yanai S, Kochi S, Kurahara K, Yao T, Torisu T, Kitazono T, Matsumoto T. Measurement of prostaglandin metabolites is useful in diagnosis of small bowel ulcerations. World J Gastroenterol 2019; 25:1753-1763. [PMID: 31011259 PMCID: PMC6465938 DOI: 10.3748/wjg.v25.i14.1753] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2019] [Revised: 02/27/2019] [Accepted: 03/11/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND We recently reported on a hereditary enteropathy associated with a gene encoding a prostaglandin transporter and referred to as chronic enteropathy associated with SLCO2A1 gene (CEAS). Crohn's disease (CD) is a major differential diagnosis of CEAS, because these diseases share some clinical features. Therefore, there is a need to develop a convenient screening test to distinguish CEAS from CD. AIM To examine whether prostaglandin E major urinary metabolites (PGE-MUM) can serve as a biomarker to distinguish CEAS from CD. METHODS This was a transactional study of 20 patients with CEAS and 98 patients with CD. CEAS was diagnosed by the confirmation of homozygous or compound heterozygous mutation of SLCO2A1. We measured the concentration of PGE-MUM in spot urine by radioimmunoassay, and the concentration was compared between the two groups of patients. We also determined the optimal cut-off value of PGE-MUM to distinguish CEAS from CD by receiver operating characteristic (ROC) curve analysis. RESULTS Twenty Japanese patients with CEAS and 98 patients with CD were enrolled. PGE-MUM concentration in patients with CEAS was significantly higher than that in patients with CD (median 102.7 vs 27.9 μg/g × Cre, P < 0.0001). One log unit increase in PGE-MUM contributed to 7.3 increase in the likelihood for the diagnosis of CEAS [95% confidence interval (CI) 3.2-16.7]. A logistic regression analysis revealed that the association was significant even after adjusting confounding factors (adjusted odds ratio 29.6, 95%CI 4.7-185.7). ROC curve analysis revealed the optimal PGE-MUM cut-off value for the distinction of CEAS from CD to be 48.9 μg/g × Cre with 95.0% sensitivity and 79.6% specificity. CONCLUSION PGE-MUM measurement is a convenient, non-invasive and useful test for the distinction of CEAS from CD.
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Affiliation(s)
- Yuichi Matsuno
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
| | - Junji Umeno
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
| | - Motohiro Esaki
- Department of Endoscopic Diagnostics and Therapeutic, Saga University Hospital, Saga 849-8501, Japan
| | - Yoichiro Hirakawa
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
- Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
| | - Yuta Fuyuno
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
| | - Yasuharu Okamoto
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
| | - Atsushi Hirano
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
| | - Shigeyoshi Yasukawa
- Department of Gastroenterology, Fukuoka University Chikushi Hospital, Chikushino 818-8502, Japan
| | - Fumihito Hirai
- Department of Gastroenterology, Fukuoka University Chikushi Hospital, Chikushino 818-8502, Japan
| | - Toshiyuki Matsui
- Department of Gastroenterology, Fukuoka University Chikushi Hospital, Chikushino 818-8502, Japan
| | - Shuhei Hosomi
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka 545-8586, Japan
| | - Kenji Watanabe
- Department of Intestinal Inflammation Research, Hyogo College of Medicine, Nishinomiya 663-8501, Japan
| | - Naoki Hosoe
- Center for Diagnostic and Therapeutic Endoscopy, School of Medicine, Keio University, Tokyo 160-0016, Japan
| | - Haruhiko Ogata
- Center for Diagnostic and Therapeutic Endoscopy, School of Medicine, Keio University, Tokyo 160-0016, Japan
| | - Tadakazu Hisamatsu
- the Third Department of Internal Medicine, Kyorin University School of Medicine, Mitaka 181-8611, Japan
| | - Shunichi Yanai
- Division of Gastroenterology, Department of Internal Medicine, Iwate Medical University, Morioka 020-8505, Japan
| | - Shuji Kochi
- Division of Gastroenterology, Matsuyama Red Cross Hospital, Matsuyama 790-8524, Japan
| | - Koichi Kurahara
- Division of Gastroenterology, Matsuyama Red Cross Hospital, Matsuyama 790-8524, Japan
| | - Tsuneyoshi Yao
- Department of Gastroenterology, Sada Hospital, Fukuoka 810-0004, Japan
| | - Takehiro Torisu
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
| | - Takanari Kitazono
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
| | - Takayuki Matsumoto
- Division of Gastroenterology, Department of Internal Medicine, Iwate Medical University, Morioka 020-8505, Japan
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Tao EW, Zou TH, Wang YF, Tang JT, Chen YX, Gao QY. Case report of cryptogenic multifocal ulcerous stenosing enteritis (CMUSE): a rare disease may contribute to endoscopy-capsule retention in the small intestine. BMC Gastroenterol 2019; 19:49. [PMID: 30943900 PMCID: PMC6448319 DOI: 10.1186/s12876-019-0962-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2019] [Accepted: 03/17/2019] [Indexed: 02/08/2023] Open
Abstract
Background CMUSE is a rare disease whose diagnosis remains difficult because the lesion is confined to the small bowel. Case presentation Here, we present a case of 43-year-old female patient suffered chronic abdominal pain for 20 years, and finally diagnosed with CMUSE. Capsule endoscopy was performed when general endoscopic investigation failed to find the lesion, but the capsule was stranded in the small intestine. Moreover, capsule retention results in acute intestinal obstruction. Thus, surgery was performed and CMUSE was confirmed. The patient was recovered after partial small intestine resection. Conclusions Capsule retention occurred in nearly 60% of patients with CMUSE. Capsule endoscopy should be avoided when the patient is suspected of CMUSE, especially with severe anemia and radiologic finding in the ileum.
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Affiliation(s)
- En-Wei Tao
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Ren-Ji Hospital, Shanghai Jiao-Tong University School of Medicine, 145 Middle Shandong Road, Shanghai, 200001, China
| | - Tian-Hui Zou
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Ren-Ji Hospital, Shanghai Jiao-Tong University School of Medicine, 145 Middle Shandong Road, Shanghai, 200001, China
| | - Yong-Feng Wang
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Ren-Ji Hospital, Shanghai Jiao-Tong University School of Medicine, 145 Middle Shandong Road, Shanghai, 200001, China
| | - Jie-Ting Tang
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Ren-Ji Hospital, Shanghai Jiao-Tong University School of Medicine, 145 Middle Shandong Road, Shanghai, 200001, China
| | - Ying-Xuan Chen
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Ren-Ji Hospital, Shanghai Jiao-Tong University School of Medicine, 145 Middle Shandong Road, Shanghai, 200001, China
| | - Qin-Yan Gao
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Ren-Ji Hospital, Shanghai Jiao-Tong University School of Medicine, 145 Middle Shandong Road, Shanghai, 200001, China.
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Yeung EH, Guan W, Mumford SL, Silver RM, Zhang C, Tsai MY, Schisterman EF. Measured maternal prepregnancy anthropometry and newborn DNA methylation. Epigenomics 2019; 11:187-198. [PMID: 30618290 DOI: 10.2217/epi-2018-0099] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
AIM We examined maternal prepregnancy anthropometry and cord blood DNA methylation. METHODS Associations between maternal measures (i.e., weight, height, waist circumference, hip circumference, skinfolds, leptin) and methylation β-values at each CpG (measured by the Infinium MethylationEPIC BeadChip) were estimated among 391 singletons. RESULTS Total of 18% of mothers were obese (body mass index ≥ 30) and 27% centrally obese (waist-to-hip ratio ≥ 0.85). One Bonferroni significant CpG with respect to obesity (cg02975187) and two with central obesity (cg12053563, cg12549355) were identified (p < 6 × 10-8). A suggestive association (p < 10-6) was observed at SFRS8 with increasing body mass index. SFRS8 was previously identified with propensity for weight gain in adults. CONCLUSION While associations identified with multiple measures related to maternal adiposity suggest different pathways, methylation differences were small in magnitude.
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Affiliation(s)
- Edwina H Yeung
- Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health & Human Development, 6710B Rockledge Drive 7004, Bethesda, MD 20817, USA
| | - Weihua Guan
- Division of Biostatistics, School of Public Health, University of Minnesota, A460 Mayo Building, MMC 303, 420 Delaware St SE, Minneapolis, MN 55455, USA
| | - Sunni L Mumford
- Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health & Human Development, 6710B Rockledge Drive 7004, Bethesda, MD 20817, USA
| | - Robert M Silver
- Department of Obstetrics & Gynecology, University of Utah, 50 North Medical Drive, Room 2B200, Salt Lake City, UT 84103, USA.,Intermountain Healthcare, Salt Lake City, 50 North Medical Drive, Salt Lake City, UT 84132, USA
| | - Cuilin Zhang
- Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health & Human Development, 6710B Rockledge Drive 7004, Bethesda, MD 20817, USA
| | - Michael Y Tsai
- Department of Laboratory Medicine & Pathology, University of Minnesota Medical School, Minneapolis, MN 55455, USA
| | - Enrique F Schisterman
- Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health & Human Development, 6710B Rockledge Drive 7004, Bethesda, MD 20817, USA
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Caruso ML, Di Pinto F, Ignazzi A, Coletta S, Valentini AM, Cavalcanti E, De Michele F. Increased nerve twigs in small intestinal mucosa with programmed cell death-ligand 1 and somatostatin receptor type 2A expression in recurrent Crohn disease: A case report. Medicine (Baltimore) 2018; 97:e13492. [PMID: 30544444 PMCID: PMC6310582 DOI: 10.1097/md.0000000000013492] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
RATIONALE Inflammatory bowel disease (IBD) patients manifest symptoms of disturbed gut function, such as neural sensory-motor changes. Programmed cell death-ligand 1 (PD-L1), normally present in neural tissue, exists in close apposition to the mucosal immune system and intestinal epithelium, and a bi-directional communication is known to occur at these interfaces. Somatostatin has been shown to suppress the inflammatory reaction, and has been used in several clinical trials to treat inflammatory disorders, such rheumatoid arthritis. Recently, somatostatin receptor type 2A, that regulates neurotransmission, proliferation, and apoptosis, has been recognized in IBD. Although prominent abnormalities in the morphology of the enteric nervous system have been observed in idiopathic IBD, they are more marked in Crohn disease. PATIENT CONCERNS A 55-year-old woman with recurrent Crohn disease, just surgically treated for ileal resection, have a stenotic complication. INTERVENTIONS At surgery 5 cm of preterminal ileum with stenosis and anastomotic ileocolic block was removed. DIAGNOSES The histopathology showed a recurrent Crohn in fistulo-stenotic phase; the stenosis was mainly sustained by mass-forming, ganglioneuromatous hyperplasia. Normally very rare, fine nerve twigs extend up into mucosa but we found a new-formed fibrillary network, extending into the inflammation area at the subepithelial luminal site of the mucosa, that was positive to PD-L1 and somatostatin receptor type 2A (SSTR2A) immunostaining but not visualized in routinary stained slides. OUTCOMES After surgery the patient was semestrally followed with clinical endoscopic evaluation that results uneventfully. LESSONS Our case shows that before surgery neuromatous abnormalities can be predicted by immunostained new-formed twigs in the mucosa.
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Eda K, Mizuochi T, Takaki Y, Ushijima K, Umeno J, Yamashita Y. Successful azathioprine treatment in an adolescent with chronic enteropathy associated with SLCO2A1 gene: A case report. Medicine (Baltimore) 2018; 97:e12811. [PMID: 30313113 PMCID: PMC6203590 DOI: 10.1097/md.0000000000012811] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
INTRODUCTION Chronic nonspecific multiple ulcers of the small intestine (CNSU), an entity with female preponderance and manifestations including anemia and hypoproteinemia reflecting persistent gastrointestinal bleeding and intestinal protein loss, has been considered idiopathic. Umeno et al recently reported that CNSU is caused by loss-of-function mutations in the solute carrier organic anion transporter family member 2A1 gene (SLCO2A1) encoding a prostaglandin transporter, renaming the disorder "chronic enteropathy associated with SLCO2A1 gene mutation" (CEAS). Treatments for chronic enteropathies such as inflammatory bowel disease, including 5-aminosalicylic acid, corticosteroids, azathioprine, and anti-tumor necrosis factor-α antibody, often are ineffective in CEAS, which frequently requires surgery. CASE PRESENTATION A 14-year-old girl had refractory anemia and hypoproteinemia for more than 2 years. Video capsule endoscopy showed nonspecific jejunal and ileal ulcers with varied sizes and shapes. She was diagnosed with CEAS resulting from compound heterozygous mutation of the SLCO2A1 gene. After corticosteroid treatment without improvement, azathioprine treatment improved her anemia and edema as hemoglobin and serum protein increased. Video capsule endoscopy 1 year after initiation of azathioprine showed improvement of small intestinal ulcers. CONCLUSION Physicians should consider CEAS in patients with refractory anemia, hypoproteinemia, and multiple small intestinal ulcers. Why our patient responded to azathioprine but not to corticosteroids is unclear, but azathioprine might benefit some other patients with CEAS.
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Affiliation(s)
- Keisuke Eda
- Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan
| | - Tatsuki Mizuochi
- Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan
| | - Yugo Takaki
- Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan
| | - Kosuke Ushijima
- Department of Pediatrics, Kurume University Medical Center, Kurume, Japan
| | - Junji Umeno
- Department of Medicine and Clinical Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan
| | - Yushiro Yamashita
- Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan
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Umeno J, Matsumoto T, Hirano A, Fuyuno Y, Esaki M. Genetic analysis is helpful for the diagnosis of small bowel ulceration. World J Gastroenterol 2018; 24:3198-3200. [PMID: 30065566 PMCID: PMC6064963 DOI: 10.3748/wjg.v24.i28.3198] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2018] [Revised: 06/07/2018] [Accepted: 06/21/2018] [Indexed: 02/06/2023] Open
Abstract
The widespread use of capsule endoscopy and balloon-assisted endoscopy has provided easy access for detailed mucosal assessment of the small intestine. However, the diagnosis of rare small bowel diseases, such as cryptogenic multifocal ulcerous stenosing enteritis (CMUSE), remains difficult because clinical and morphological features of these diseases are obscure even for gastroenterologists. In an issue of this journal in 2017, Hwang et al reviewed and summarized clinical and radiographic features of 20 patients with an established diagnosis of CMUSE. Recently, recessive mutations in the PLA2G4A and SLCO2A1 genes have been shown to cause small intestinal diseases. The small bowel ulcers in each disease mimic those in the other and furthermore those found in nonsteroidal anti-inflammatory drug-induced enteropathy. These recent and novel findings suggest that a clinical diagnosis exclusively based on the characteristics of small bowel lesions is possibly imprecise. Genetic analyses seem to be inevitable for the diagnosis of rare small bowel disorders such as CMUSE.
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Affiliation(s)
- Junji Umeno
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Fukuoka 812-8582, Japan
| | - Takayuki Matsumoto
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Iwate Medical University, Morioka, Iwate 020-8505, Japan
| | - Atsushi Hirano
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Fukuoka 812-8582, Japan
| | - Yuta Fuyuno
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Fukuoka 812-8582, Japan
| | - Motohiro Esaki
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Fukuoka 812-8582, Japan
- Department of Endoscopic Diagnostics and Therapeutics, Saga University Hospital, Saga 849-8501, Japan
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