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Cryptogenic Multifocal Ulcerating Stenosing Enteropathy(CMUSE) and/or Chronic Non-specific Multiple Ulcers of the Small Intestine(CNSU) and Non-granulomatous Ulcerating Jejunoileitis (NGUJI)

  • Ayaskanta SinghEmail author
Small Intestine (D Sachar, Section Editor)
  • 26 Downloads
Part of the following topical collections:
  1. Topical Collection on Small Intestine

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.

Summary

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.

Keywords

Chronic stenosing enteropathy Chronic enteropathy associated with the SLCO2A1 gene (CEAS) Neuromuscular and vascular hamartoma (NVHM) Capsule endoscopy 

Notes

Compliance with Ethical Standards

Conflict of Interest

The author declares that there is no conflict of interest.

Human and Animal Rights and Informed Consent

All reported studies/experiments with human or animal subjects performed by the author have been previously published and complied with all applicable ethical standards.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Debray C, Besancon F, Hardouin JP, Martin E, Marche C, Khoury K. Cryptogenetic plurifocal ulcerative stenosing enteritis. Arch Mal Appar Dig Mal Nutr. 1964;53:193–206.PubMedGoogle Scholar
  2. 2.
    • Perlemuter G, Guillevin L, Legman P, Weiss L, Couturier D, Chaussade S. Cryptogenetic multifocal ulcerous stenosing enteritis: an atypical type of vasculitis or a disease mimicking vasculitis. Gut. 2001;48:333–8. Initial paper which gives a comprehensive review and also tries to explain the pathogenesis of CMUSE. CrossRefGoogle Scholar
  3. 3.
    • Matsumoto T, Iida M, Matsui T, Yao T. Chronic nonspecific multiple ulcers of the small intestine: a proposal of the entity from Japanese gastroenterologists to Western enteroscopists. Gastrointest Endosc. 2007;66(3 Suppl):S99–S107. The term CNSU is coined in Japan. CrossRefGoogle Scholar
  4. 4.
    •• Umeno J, Hisamatsu T, Esaki M, Hirano A, Kubokura N, Asano K, et al. A hereditary enteropathy caused by mutations in the SLCO2A1 gene, encoding a prostaglandin transporter. PLoS Genet. 2015;11(11):e1005581. Landmark paper where the genetic basis of the disease is identified and the term CEAS is coined. CrossRefGoogle Scholar
  5. 5.
    •• Hosoe N, Ohmiya N, Hirai F, Umeno J, Esaki M, Yamagami H, et al. Chronic enteropathy associated with SLCO2A1 gene [CEAS]—characterisation of an enteric disorder to be considered in the differential diagnosis of Crohn’s disease. J Crohn’s Colitis. 2017;11(10):1277–81.  https://doi.org/10.1093/ecco-jcc/jjx068. Large multicentric study from Japan, where 20 patients of CEAS are described. Validates that CNSU are autosomal recessive and occur due to mutation in the SLCO2A1 gene. CrossRefGoogle Scholar
  6. 6.
    Sun X, Hosoe N, Miyanaga R, Kimura K, Mizuno S, Takabayashi K, et al. A male Korean who was diagnosed with chronic enteropathy associated with SLCO2A1 (CEAS): case report with literature review. BMJ Open Gastroenterol. 2018;5:e000223.  https://doi.org/10.1136/bmjgast-2018-000223.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Hopkins JE, Deaver JM. Stenosing small-bowel ulceration. Pa Med. 1966;69(8):35–9.PubMedGoogle Scholar
  8. 8.
    Lindholmer B, Nyman E, Raef L. Nonspecific stenosing ulceration of the small bowel: a preliminary report. Acta Chir Scand. 1964;128:310–1.PubMedGoogle Scholar
  9. 9.
    Rocha A, Artigas V. Stenosing ulcerous disease of the jejuno-ileum. Arch Mal Appar Dig Mal Nutr. 1959;48:1230–6 (French).PubMedGoogle Scholar
  10. 10.
    •• Kohoutová D, Bures J, Tycová V, Bártová J, Tachecí I, Rejchrt S, et al. Severe cryptogenic multifocal ulcerous stenosing enteritis. A report of three cases and review of the literature. Acta Medica (Hradec Kralove). 2010;53(53):25–9. Comprehensive review paper on CMUSE. CrossRefGoogle Scholar
  11. 11.
    Chang DK, Kim JJ, Choi H, Eun CS, Han DS, Byeon JS, et al. Double balloon endoscopy in small intestinal Crohn’s disease and other inflammatory diseases such as cryptogenic multifocal ulcerous stenosing enteritis (CMUSE). Gastrointest Endosc. 2007;66(3):S96–8.CrossRefGoogle Scholar
  12. 12.
    •• Hwang J, Kim JS, Kim AY, Lim JS, Kim SH, Kim MJ, et al. Cryptogenic multifocal ulcerous stenosing enteritis: radiologic features and clinical behavior. World J Gastroenterol. 2017;23:4615–23.  https://doi.org/10.3748/wjg.v23.i25.4615. Recent large case series on CMUSE patients. CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Singh A, Sahu MK, Panigrahi MK, Misra D. Cryptogenic multifocal ulcerous Stenosing enteritis (CMUSE): a tale of three decades. ACG Case Rep J. 2017;4:e44.CrossRefGoogle Scholar
  14. 14.
    Kim CW, Yu CS, Yoon YS, Yoon SN, Lim SB, Kim JC, et al. Steroid-refractory cryptogenic multifocal ulcerous stenosing enteritis. Am J Surg. 2011;202:e48–51.CrossRefGoogle Scholar
  15. 15.
    Yang Y, Zhao L, Zhang Y. A steroid-resistant cryptogenic multifocal ulcerous stenosing enteritis. Niger J Clin Pract. 2018;21:678–80.CrossRefGoogle Scholar
  16. 16.
    Kijmassuwan T, Tanpowpong P, Molagool S, Treepongkaruna S. A rare cause of multiple small bowel ulcers and strictures in a 10-year-old child. Turk J Gastroenterol. 2018;29:112–5.CrossRefGoogle Scholar
  17. 17.
    Freeman HJ. Multifocal stenosing ulceration of the small intestine. World J Gastroenterol. 2009;15(39):4883–5.  https://doi.org/10.3748/wjg.15.4883.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Fernando SS, McGovern VJ. Neuromuscular and vascular hamartoma of small bowel. Gut. 1982;23:1008–12.CrossRefGoogle Scholar
  19. 19.
    Smith CE, Filipe MI, Owen WJ. Neuromuscular and vascular hamartoma of small bowel presenting as inflammatory bowel disease. Gut. 1986;27:964–9.CrossRefGoogle Scholar
  20. 20.
    • Setaffy L, Osuna MJ, Plieschnegger W, et al. Cryptogenic multifocal ulcerous stenosing enteritis (CMUSE), and neuromuscular and vascular hamartoma (NMVH): two sides of the same coin? Endoscopy. 2015;47:345–8. Elucidated that CMUSE and NMVH are similar diseases. PubMedGoogle Scholar
  21. 21.
    Perlemuter GA, Chaussade ST, Soubrane OL, Degoy AN, Louvel AN, Barbet PI, et al. Multifocal stenosing ulcerations of the small intestine revealing vasculitis associated with C2 deficiency. Gastroenterology. 1996;110(5):1628–32.CrossRefGoogle Scholar
  22. 22.
    Matsumoto T, Kubokura N, Matsui T, Iida M, Yao T. Chronic nonspecific multiple ulcer of the small intestine segregates in offspring from consanguinity. J Crohns Colitis. 2011;5:559–65.CrossRefGoogle Scholar
  23. 23.
    Esaki M, Umeno J, Kitazono T, Matsumoto T. Clinicopathologic features of chronic nonspecific multiple ulcers of the small intestine. Clin J Gastroenterol. 2015;8:57–62.CrossRefGoogle Scholar
  24. 24.
    Brooke MA, Longhurst HJ, Plagnol V, Kirkby NS, Mitchell JA, Rüschendorf F, et al. Cryptogenic multifocal ulcerating stenosing enteritis associated with homozygous deletion mutations in cytosolic phospholipase A2-α. Gut. 2014;63:96–104.  https://doi.org/10.1136/gutjnl-2012-303581.CrossRefPubMedGoogle Scholar
  25. 25.
    Zhang Y, Huang L, Liu R, Wang M, Jiang Z, Zhou W, et al. Case report of a pair of siblings with cryptogenic multifocal ulcerating stenosing enteritis: a rare disease easily to be misdiagnosed as Crohn disease. Medicine. 2017;96(32).CrossRefGoogle Scholar
  26. 26.
    Fraile G, Norman F, Reguero ME, Defargues V, Redondo C. Cryptogenic multifocal ulcerous stenosing enteritis (CMUSE) in a man with a diagnosis of X-linked reticulate pigmentary disorder(PDR). Scand J Gastroenterol. 2008;43:506–10.CrossRefGoogle Scholar
  27. 27.
    Adler DH, Cogan JD, Phillips JA 3rd, Schnetz-Boutaud N, Milne GL, Iverson T, et al. Inherited human cPLA(2alpha) deficiency is associated with impaired eicosanoid biosynthesis, small intestinal ulceration, and platelet dysfunction. J Clin Invest. 2008;118:2121–31.  https://doi.org/10.1172/JCI30473.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    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(28):3198–200 Available from: http://www.wjgnet.com/1007-9327/full/v24/i28/3198.htm.  https://doi.org/10.3748/wjg.v24.i28.3198.CrossRefGoogle Scholar
  29. 29.
    • Umeno J, Esaki M, Hirano A, Fuyuno Y, Ohmiya N, Yasukawa S, et al. Clinical features of chronic enteropathy associated with SLCO2A1 gene: a new entity clinically distinct from Crohn’s disease. J Gastroenterol. 2018;53(8):907–15. Recent multicentric genetic study. CrossRefGoogle Scholar
  30. 30.
    Uchida K, Nakajima A, Ushijima K, Ida S, Seki Y, Kakuta F, et al. Pediatric-onset chronic nonspecific multiple ulcers of small intestine: a nationwide survey and genetic study in Japan. J Pediatr Gastroenterol Nutr. 2017;64(4):565–8.CrossRefGoogle Scholar
  31. 31.
    Niizeki H, Shiohama A, Sasaki T, Seki A, Kabashima K, Otsuka A, et al. The complete type of pachydermoperiostosis: a novel nonsense mutation p. E141* of the SLCO2A1 gene. J Dermatol Sci. 2014;75(3):193–5.CrossRefGoogle Scholar
  32. 32.
    Zhang Z, Xia W, He J, Zhang Z, Ke Y, Yue H, et al. Exome sequencing identifies SLCO2A1 mutations as a cause of primary hypertrophic osteoarthropathy. Am J Hum Genet. 2012 Jan 13;90(1):125–32.CrossRefGoogle Scholar
  33. 33.
    Iddan G, Meron G, Glukhovsky A, Swain P. Wireless capsule endoscopy. Nature. 2000;405(6785):417.CrossRefGoogle Scholar
  34. 34.
    Yamamoto H, Sekine Y, Sato Y, Higashizawa T, Miyata T, Iino S, et al. Total enteroscopy with a nonsurgical steerable double-balloon method. Gastrointest Endosc. 2001;53(2):216–20.CrossRefGoogle Scholar
  35. 35.
    May A, Nachbar L, Wardak A, Yamamoto H, Ell C. Double-balloon enteroscopy: preliminary experience in patients with obscure gastrointestinal bleeding or chronic abdominal pain. Endoscopy. 2003;35(12):985–91.CrossRefGoogle Scholar
  36. 36.
    Tsukahara H, Kumagai H, Yano T, Maisawa SI. A 4-year-old girl with chronic nonspecific multiple ulcers of the small intestine diagnosed by double-balloon endoscopy. Clin J Gastroenterol. 2014;7(2):144–7.CrossRefGoogle Scholar
  37. 37.
    •• 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(1):49. Recent paper which suggests capsule endoscopy should be used with caution in CMSE/CNSU patients. CrossRefGoogle Scholar
  38. 38.
    Chung SH, Jo Y, Ryu SR, Ahn SB, Son BK, Kim SH, et al. Diaphragm disease compared with cryptogenic multifocal ulcerous stenosing enteritis. World J Gastroenterol: WJG. 2011;17(23):2873–6.PubMedGoogle Scholar
  39. 39.
    Santolaria S, Cabezali R, Ortego J, Castiella T, Salinas JC, Lanas A. Diaphragm disease of the small bowel: a case without apparent nonsteroidal anti-inflammatory drug use. J Clin Gastroenterol. 2001;32:344–6.CrossRefGoogle Scholar
  40. 40.
    Matsumoto T, Nakamura S, Esaki M, Yada S, Koga H, Yao T, et al. Endoscopic features of chronic nonspecific multiple ulcers of the small intestine: comparison with nonsteroidal anti-inflammatory drug-induced enteropathy. Dig Dis Sci. 2006;51(8):1357–63.CrossRefGoogle Scholar
  41. 41.
    Matsumoto T, Iida M, Matsui T, Yao T, Watanabe H, Okabe H. Non-specific multiple ulcers of the small intestine unrelated to non-steroidal anti-inflammatory drugs. J Clin Pathol. 2004;57(11):1145–50.CrossRefGoogle Scholar
  42. 42.
    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. 2018;97(41).CrossRefGoogle Scholar
  43. 43.
    • De Schepper H, Macken E, Van Marck V, Spinhoven M, Pelckmans P, Moreels T. Infliximab induces remission in cryptogenic multifocal ulcerous stenosing enteritis: First case. World J Gastroenterol. 2013;19(10):1661. Promising paper which shows TNF antagonist may be helpful in CMUSE patients. CrossRefGoogle Scholar
  44. 44.
    • Jeffries GH, Steinberg H, Sleisenger MH. Chronic ulcerative (non granulomatous) jejunitis. Am J Med. 1968;44:47–59. NGUJI was first described and the diagnostic criteria are laid down. CrossRefGoogle Scholar
  45. 45.
    Modigliani R, Poitras P, Galian A, Messing B, Guyet-Rousset P, Libeskind M, et al. Chronic non-specific ulcerative duodenojejunoileitis: report of four cases. Gut. 1979;20(4):318–28.CrossRefGoogle Scholar
  46. 46.
    Enns R, Lay T, Bridges R. Use of azathioprine for nongranulomatous ulcerative jejunoileitis. Can J Gastroenterol. 1997;11:503–6.CrossRefGoogle Scholar
  47. 47.
    Freeman M, Cho SR. Nongranulomatous ulcerative jejunoileitis. Am J Gastroenterol. 1984;79:446–9.PubMedGoogle Scholar
  48. 48.
    Saxon A, Stevens RH, Ashman RF, Parker NH. Dual immune defects in nongranulomatous ulcerative jejunoileitis with hypogammaglobulinemia. Clin Immunol Immunopathol. 1977;8:272–9.CrossRefGoogle Scholar
  49. 49.
    Corlin RF, Pops MA. Nongranulomatous ulcerative jejunoileitis with hypogammaglobulinemia. Clinical remission after treatment with -globulin. Gastroenterology. 1972;62:473–8.CrossRefGoogle Scholar
  50. 50.
    Seven G, Assaad A, Biehl T, Kozarek RA. Use of anti tumor necrosis factor-alpha monoclonal antibody for ulcerative jejunoileitis. World J Gastroenterol: WJG. 2012;18(36):5135.CrossRefGoogle Scholar
  51. 51.
    Sigman T, Nguyen VH, Costea F, Sant’Anna A, Seidman EG. Ulcerative jejunitis in a child with celiac disease. BMC Gastroenterol. 2014;14(1):29.CrossRefGoogle Scholar
  52. 52.
    Moon H, Kim YS, Chung YJ, Kim KA, Kim KM, Park MJ, et al. Three cases of chronic nongranulomatous ulcerative jejunoileitis. Korean J Gastroenterol. 1999;34(3):399–405.Google Scholar
  53. 53.
    Kim HH, Kim YS, Ok KS, Ryu SH, Lee JH, Moon JS, et al. Chronic non-granulomatous ulcerative jejunoileitis assessed by wireless capsule endoscopy. Korean J Gastroenterol. 2010;56(6):382–6.CrossRefGoogle Scholar
  54. 54.
    LePane CA, Barkin JS, Parra J, Simon T. Ulcerative jejunoileitis: a complication of celiac sprue simulating Crohn’s disease diagnosed with capsule endoscopy (PillCam). Dig Dis Sci. 2007;52:698–701.CrossRefGoogle Scholar
  55. 55.
    Enns R, Lay T, Bridges R. Use of axathioprine for nongranulomatous ulcerative jejunoileitis. Can J Gastroenterol Hepatol. 1997;11(6):503–6.Google Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Gastroenterology and Hepatobiliary Sciences, IMS and SUM Hospital Siksha ‘O’ Anusandhan, deemed to be UniversityBhubaneswarIndia

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