Comorbid Inflammatory Diseases of Digestive System and Eye

Crohn’s disease and ulcerative colitis are chronic inflammatory bowel diseases, which are often accompanied by inflammation of other organs. This article presents modern data on etiology, pathogenesis and clinical course of inflammatory bowel diseases, as well as information on extraintestinal eye manifestations of nonspecific ulcerative colitis and Crohn’s disease. The role of microbiota, genetic factors, immune system defects in pathogenesis of intestinal inflammation and extraintestinal eye manifestations is considered. The possibility the development of ophthalmopathology not only against the background of intestinal inflammation, but also as a consequence of therapeutic and surgical methods of treatment of ulcerative colitis and Crohn’s disease is noted. The peculiarities of the course of episcleritis/scleritis, keratitis, uveitis, chorioretinitis, optical neuritis for patients with inflammatory bowel diseases are considered. The presence of these complications may reflect the activity of the underlying disease, which in some cases requires correction of therapy. Anterior uveitis and episcleritis/scleritis are the most common extraintestinal manifestations of inflammatory bowel disease. Inflammation of tissues of the posterior segment of the eye and optic nerve against the background of ulcerative colitis and Crohn’s disease are less common, but are of clinical importance, as they can catastrophically damage the structures of the eye and, as a consequence, lead to complete blindness. Considering the possibility of mild clinical symptoms and asymptomatic course of inflammation in the eye envelopes, the importance of ophthalmological examination of all patients with ulcerative colitis and Crohn’s disease is emphasized. Aspects of modern therapy of ophthalmopathology and background intestinal inflammation are highlighted. Biological preparations — antagonists of pro-inflammatory cytokines — have been identified as the most promising in the treatment of inflammatory intestinal diseases and extraintestinal manifestations. The important role of proper nutrition and biologically active supplements containing omega-3 fatty acids, vitamin D, microelements, was noted as auxiliary therapy of both intestinal and extraintestinal inflammation.

1. Ghanchi F.D., Rembacken B.J. Inflammatory bowel disease and the eye. Survey of ophthalmology. 2003;48(6):663–676. DOI: 10.1016/j.survophthal.2003.08.004

2. Vavricka S.R., Brun L., Ballabeni P., Pittet V., Prinz Vavricka B.M., Zeitz J., Rogler G., Schoepfer A.M. Frequency and risk factors for extraintestinal manifestations in the Swiss inflammatory bowel disease cohort. The American journal of gastroenterology. 2011;106:110–119. DOI: 10.1038/ajg.2010.343

3. Veloso F.T., Carvalho J., Magro F. Immune-related systemic manifestations of inflammatory bowel disease. A prospective study of 792 patients. Journal of clinical gastroenterology. 1996;23:29–34. DOI: 10.1097/00004836-199607000-00009

4. Charpentier C., Chan R., Salameh E., Mbodji K., Ueno A., Coëffier M., Guerin C., Ghosh S., Savoye G., Marion-Letellier R. Dietary n-3 pufa may attenuate experimental colitis. Mediators of inflammation. 2018:8430614. DOI: 10.1155/2018/8430614

5. Nielsen A.A., Jorgensen L.G., Nielsen J.N., Eivindson M., Gronbaek H., Vind I., Hougaard D.M., Skogstrand K., Jensen S., Munkholm P., Brandslund I., Hey H. Omega-3 fatty acids inhibit an increase of proinflammatory cytokines in patients with active Crohn’s disease compared with omega-6 fatty acids. Alimentary pharmacology and therapeutics. 2005;22(11–12):1121–1128. DOI: 10.1111/j.13652036.2005.02698.x

6. Rosenbaum J.T., Asquith M. The microbiome and HLA-B27-associated acute anterior uveitis. Nature reviews. Rheumatology. 2018;14(12):704–713. DOI: 10.1038/s41584-018-0097-2

7. Marchesi J.R., Ravel J. The vocabulary of microbiome research: a proposal. Microbiome. 2015;3:31. DOI: 10.1186/s40168-015-0094-5

8. Ley R.E., Hamady M., Lozupone C., Peter J., Turnbaugh P.J., Ramey R.R., Bircher J.S., Schlegel M.L., Tucker T.A., Schrenzel M.D., Knight R., Gordon J.I. Evolution of mammals and their gut microbes. Science. 2008; 320(5883):1647–1651. DOI: 10.1126/science.1155725

9. Costello M.E., Ciccia F., Willner D., Warrington N., Robinson P.C., Gardiner B., Marshall M., Kenna T.J., Triolo G., A Brown M.A. Brief report: intestinal dysbiosis in ankylosing spondylitis. Arthritis and rheumatology. 2015;67(3):686–691. DOI: 10.1002/art.38967

10. Girbovan A., Sur G., Samasca G., Lupan I. Dysbiosis a risk factor for celiac disease. Medical microbiology and immunology. 2017; 206(2): 83–91. DOI: 10.1007/s00430017-0496-z

11. Morgan X.C., Tickle T.L., Sokol H., Gevers D., Devaney K.L., Ward D.V., Reyes J.A., Shah S.A., LeLeiko N., Snapper S.B., Bousvaros A., Korzenik J., Sands B.E., Xavier R.J., Huttenhower C. Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment. Genome biology. 2012;13(9):R79. DOI: 10.1186/gb2012-13-9-r79

12. Ohkusa T., Sato N., Ogihara T., Morita K., Ogawa M., Okayasu I. Fusobacterium varium localized in the colonic mucosa of patients with ulcerative colitis stimulates species-specific antibody. Journal of gastroenterology and hepatology. 2002;17(8):849–853. DOI: 10.1046/j.1440-1746.2002.02834.x

13. Sartor R.B. Therapeutic manipulation of the enteric microflora in inflammatory bowel diseases: antibiotics, probiotics, and prebiotics. Gastroenterology. 2004;126(6):1620–1633. DOI: 10.1053/j.gastro.2004.03.024

14. Sellon R.K., Tonkonogy S., Schultz M., Dieleman L.A., Grenther W., Balish E., Rennick D.M., Sartor R.B. Resident enteric bacteria are necessary for development of spontaneous colitis and immune system activation in interleukin-10-deficient mice. Infection and immunity. 1998;66(11):5224–5231. DOI: 10.1128/IAI.66.11.5224-5231.1998

15. Sheehan D., Moran C., Shanahan F. The microbiota in inflammatory bowel disease. Journal of gastroenterology. 2015;50(5):495–507. DOI: 10.1007/s00535-015-1064-1

16. Tedelind S., Westberg F., Kjerrulf M., Vidal A. Anti-inflammatory properties of the short-chain fatty acids acetate and propionate: a study with relevance to inflammatory bowel disease. World journal of gastroenterology. 2007;13(20):2826–2832. DOI: 10.3748/wjg.v13.i20.2826

17. Smith P.M., Howitt M.R., Panikov N., Michaud M., Gallini C.A., Bohlooly-Y M., Glickman J.N., Garrett W.S. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science. 2013;341(6145):569–573. DOI: 10.1126/science.1241165

18. Sokol H., Pigneur B., Watterlot L., Lakhdari O., Bermudez-Humaran L.G., Gratadoux J.J., Blugeon S., Bridonneau C., Furet J.P., Corthier G., Grangette C., Vasquez N., Pochart P., Trugnan G., Thomas G., Blottiere H.M., Dore J., Marteau P., Seksik P., Langella P. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proceedings of the National Academy of Sciences of the United States of America. 2008;105(43):16731–16736. DOI: 10.1073/pnas.0804812105

19. Zhang C., Zhang M., Wang S., Han R., Cao Y., Hua W., Mao Y., Zhang X., Pang X., Wei C., Zhao G., Chen Y., Zhao L. Interaction between gut microbiota, host genetics and diet relevant to development of metabolic syndrome in mice. The ISME journal. 2010;4(2):232–241. DOI: 10.1038/ismej.2009.112

20. Devkota S., Wang Y., Musch M.W., Leone V., Fehlner-Peach H., Nadimpalli A., Antonopoulos D.A., Jabri B., Chang E.B. Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10−/− mice. Nature. 2012;487(7405):104–108. DOI: 10.1038/nature11225

21. Clarke S.F., Murphy E.F., Nilaweera K., Ross P.R., Shanahan F., O’Toole P.W., Cotter P.D. The gut microbiota and its relationship to diet and obesity: New insights. Gut Microbes. 2012;3(3):186–202. DOI: 10.4161/gmic.20168

22. Noriega B.S., Sanchez-Gonzalez M.A., Salyakina D., Coffman J. Understanding the impact of omega-3 rich diet on the gut microbiota. Case reports in medicine. 2016:3089303. DOI: 10.1155/2016/3089303

23. Menni C., Zierer J., Pallister T., Jackson M.A., Long T., Mohney R.P., Steves C.J., Spector T.D., Valdes A.M. Omega-3 fatty acids correlate with gut microbiome diversity and production of N-carbamylglutamate in middle aged and elderly women. Scientific reports. 2017; 7(1):11079. DOI: 10.1038/s41598-017-10382-2

24. Mokkala K., Roytio H., Munukka E., Pietila S., Ekblad U., Ronnemaa T., Eerola E., Laiho A., Laitinen K. Gut microbiota richness and composition and dietary intake of overweight pregnant women are related to serum zonulin concentration, a marker for intestinal permeability. The Journal of nutrition. 2016;146(9):1694–1700. DOI: 10.3945/jn.116.235358

25. Bashir M., Prietl B., Tauschmann M., Mautner S.I., Kump P.K., Treiber G., Wurm P., Gorkiewicz G., Högenauer C., Pieber T.R. Effects of high doses of vitamin D3 on mucosa-associated gut microbiome vary between regions of the human gastrointestinal tract. European journal of nutrition. 2016;55(4):1479–1489. DOI: 10.1007/s00394-015-0966-2

26. Garg M., Hendy P., Ding J.N., Shaw S., Hold G., Hart A. The effect of vitamin D on intestinal inflammation and faecal microbiota in patients with ulcerative colitis. Journal of Crohn’s and colitis. 2018;12(8):963–972. DOI: 10.1093/ecco-jcc/jjy052

27. Vavricka S.R., Schoepfer A., Scharl M., Lakatos P.L., Navarini A., Rogler G. Extraintestinal manifestations of inflammatory bowel disease. Inflammatory bowel diseases. 2015;21(8):1982-1992. DOI: 10.1097/MIB.0000000000000392.

28. Rankin G.B., Watts H.D., Melnyk C.S., Kelley Jr M.L. National cooperative Crohn’s disease study: extraintestinal manifestations and perianal complications. Gastroenterology. 1979;77(4 Pt 2):914–920.

29. Bernstein C.N., Blanchard J.F., Rawsthorne P., Yu N. The prevalence of extraintestinal diseases in inflammatory bowel disease: a population-based study. The American journal of gastroenterology. 2001;96(4):1116–1122. DOI: 10.1111/j.15720241.2001.03756.x

30. Orchard T.R., Chua C.N., Ahmad T., Cheng H., Welsh K.I., Jewell D.P. Uveitis and erythema nodosum in inflammatory bowel disease: clinical features and the role of HLA genes. Gastroenterology. 2002;123(3):714–718. DOI: 10.1053/gast.2002.35396

31. Fine S., Nee J., Thakuria P., Duff B., Farraye F.A., Shah S.A. Ocular, auricular, and oral manifestations of inflammatory bowel disease. Digestive diseases and sciences. 2017;62(12):3269–3279. DOI: 10.1007/s10620-017-4781-x

32. Ungaro R., Mehandru S., Allen P.B., Peyrin-Biroulet L., Colombel J.F. Ulcerative colitis. Lancet. 2017;389(10080):1756–1770. DOI: 10.1016/S0140-6736(16)32126-2

33. Troncoso L.L., Biancardi A.L., de Moraes H.V. Jr, Zaltman C. Ophthalmic manifestations in patients with inflammatory bowel disease: A review. World journal of gastroenterology. 2017;23(32):5836–5848. DOI: 10.3748/wjg.v23.i32.5836

34. Trukhan D.I., Tarasova L.V., Lebedev O.I., Safonov A.D. Eyes’ symptoms of the digestive diseases. Experimental and clinical gastroenterology = Eksperimental’naya i klinicheskaya gastroenterologiya. 2014;10(110):83–87 (In Russ.).

35. Mintz R., Feller E.R., Bahr R.L., Shah S.A. Ocular manifestations of inflammatory bowel disease. Inflammatory bowel diseases. 2004;10(2):135–139. DOI: 10.1097/00054725-200403000-00012

36. Obrubov S.A., Demidova M.Yu., Delyagin M.V., Karpina L.M., Svirchevsky I.V., Bespalyuk Yu.G., Ivanova A.O. Eye pathology in chronic inflammatory intestinal diseases in children. Russian Bulletin of perinatology and pediatrics = Rossiiskiy vestnik perinatologii i pediatrii. 2008;53(4):73–77 (In Russ.).

37. Orchard T.R., Chua C.N., Ahmad T., Cheng H., Welsh K.I., Jewell D.P. Uveitis and erythema nodosum in inflammatory bowel disease: clinical features and the role of HLA genes. Gastroenterology. 2002;123(3):714–718. DOI: 10.1053/gast.2002.35396

38. Mendoza J.L., Lana R., Taxonera C., Alba C., Izquierdo S., Díaz-Rubio M. Extraintestinal manifestations in inflammatory bowel disease: differences between Crohn’s disease and ulcerative colitis. Medicina clínica (Barc). 2005;125(8):297–300. DOI: 10.1157/13078423

39. Brazilian Study Group of Inflammatory Bowel Diseases. Consensus guidelines for the management of inflammatory bowel disease. Arquivos de gastroenterologia. 2010;47(3):313–325. DOI: 10.1590/s0004-28032010000300019

40. Ghanchi F.D., Rembacken B.J. Inflammatory bowel disease and the eye. Survey of ophthalmology. 2003 Nov-Dec;48(6):663–676. DOI: 10.1016/j.survophthal.2003.08.004

41. Salmon J.F., Wright J.P., Murray A.D. Ocular inflammation in Crohn’s disease. Ophthalmology. 1997;98:480–484. DOI: 10.1016/s0161-6420(91)32268-1

42. Danese S., Semeraro S., Papa A., Roberto I., Scaldaferri F., Fedeli G., Gasbarrini G., Gasbarrini A. Extraintestinal manifestations in inflammatory bowel disease. World journal of gastroenterology. 2005;11(46):7227–7236. DOI: 10.3748/wjg.v11.i46.7227

43. McCannel C.A., Holland G.N., Helm C.J., Cornell P.J., Winston J.V., Rimmer T.G. Causes of uveitis in the general practice of ophthalmology. American journal of ophthalmology. 1996;121(1):35–46. DOI: 10.1016/s0002-9394(14)70532-x

44. Banares A., Jover J.A., Fernandez-Gutierrez B. Pattern of uveitis as guide in making rheumatologic and immunologic diagnosis. Arthritis and rheumatism. 1997;40(2):358-370. DOI: 10.1002/art.1780400221

45. Pasadhika S., Rosenbaum J.T. Update on the use of systemic biologic agents in the treatment of noninfectious uveitis. Biologics. 2014;8:67–81. DOI: 10.2147/BTT.S41477

46. Czompa L., Barta Z., Ziad H., Nemeth G., Rentka A., Aszalos Z., Zold E., Gesztelyi R., Zsuga J., Szodoray P., Kemeny-Beke A. Corneal manifestations of inflammatory bowel disease. Seminars in ophthalmology. 2019;34(7–8):543–550. DOI: 10.1080/08820538.2019.1684525

47. Gomes B.A., Santhiago M.R., Jorge P.A., Kara-José N., Moraes H.V. Jr, Kara-Junior N. Corneal involvement in systemic inflammatory diseases. Eye Contact Lens. 2015;41(3):141–144. DOI: 10.1097/ICL.0000000000000141

48. Czompa L., Barta Z., Ziad H., Nemeth G., Rentka A., Aszalos Z., Zold E., Gesztelyi R., Zsuga J., Szodoray P., Kemeny-Beke A. Corneal manifestations of inflammatory bowel disease. Seminars in ophthalmology. 2019;34(7–8):543–550. DOI: 10.1080/08820538.2019.1684525

49. Ellis P.P., Gentry J.H. Ocular complications of ulcerative colitis. American journal of ophthalmology. 1964;58:779–785.

50. Knox D.L., Snip R.C., Stark W.J. The keratopathy of Crohn’s disease. American journal of ophthalmology. 1980;90(6):862–865. DOI: 10.1016/s0002-9394(14)75202-x

51. Macoul K.L. Ocular changes in granulomatous ileocolitis. Archives of ophthalmology. 1997;1970:95–97. DOI: 10.1001/archopht.1970.00990040097023

52. Ceresara G., Fogagnolo P., De Cillà S., Panizzo V., Danelli P.G., Orzalesi N., Rossetti L. Corneal involvement in Crohn’s disease: an in vivo confocal microscopy study. Cornea. 2011;30(2):136–142. DOI: 10.1097/ICO.0b013e3181e9ac98

53. Petrey A.C., de la Motte C.A. The extracellular matrix in IBD: a dynamic mediator of inflammation. Current opinion in gastroenterology. 2017;33(4):234–238. DOI: 10.1097/MOG.0000000000000368

54. O’Sullivan S., Gilmer J.F., Medina C. Matrix metalloproteinases in inflammatory bowel disease: an update. Mediators of inflammation. 2015;2015:964131. DOI: 10.1155/2015/964131

55. Ma J., Wang Y., Wei P., Jhanji V. Biomechanics and structure of the cornea: implications and association with corneal disorders. Survey of ophthalmology. 2018;63(6):851–861. DOI: 10.1016/j.survophthal.2018.05.004

56. Ernst B.B., Lowder C.Y., Meisler D.M., Gutman F.A. Posterior segment manifestations of inflammatory bowel disease. Ophthalmology. 1991;98(8):1272–1280. DOI: 10.1016/s0161-6420(91)32143-2

57. Katsanos A., Asproudis I., Katsanos K.H., Dastiridou A.I., Aspiotis M., Tsianos E.V. Orbital and optic nerve complications of inflammatory bowel disease. Journal of Crohn’s and colitis. 2013;7(9):683–693. DOI: 10.1016/j.crohns.2012.09.020

58. Chan J.W., Castellanos A. Infliximab and anterior optic neuropathy: case report and review of the literature. Graefe’s archive for clinical and experimental ophthalmology. 2010;248(2):283–287. DOI: 10.1007/s00417-009-1227-y

59. Puli S.R., Benage D.D. Retinal vein thrombosis after infliximab (Remicade) treatment for Crohn’s disease. The American journal of gastroenterology. 2003;98(4):939– 940. DOI: 10.1111/j.1572-0241.2003.07368.x

60. You C., Sahawneh H.F., Ma L., Kubaisi B., Schmidt A., Foster C.S. A review and update on orphan drugs for the treatment of noninfectious uveitis. Clinical ophthalmology. 2017;11:257–265. DOI: 10.2147/OPTH.S121734

61. Astakhov S.Yu., Gobedzhishvili M.V. Non-steroidal anti-inflammatory drugs in the post-operative treatment of ophthalmic patients. Ophthalmology journal = Oftal’mologicheskie vedomosti. 2015;8(3):45–48 (In Russ.).

62. Proskurina O.V. Use of short-term cycloplegia in children’s ophthalmological practice. Russian Medical Journal. Clinical Ophthalmology = Rossijskiy medicinskiy zhurnal. Klinicheskaya oftal’mologiya. 2007;8(4):152 (In Russ.).

63. Ford A.C., Achkar J-P, Khan K.J., Kane S.V., Talley N.J., Marshall J.K., et al. Efficacy of 5-aminosalicylates in ulcerative colitis: systematic review and meta-analysis. The American journal of gastroenterology. 2011;106(4):601–616. DOI: 10.1038/ajg.2011.67

64. Mahgoub A., El-Medany A., Mustafa A., Arafah М., Moursi M. Azithromycin and erythromycin ameliorate the extent of colonic damage induced by acetic acid in rats. Toxicology and applied pharmacology. 2005;205(1):43–52. DOI: 10.1016/j.taap.2004.09.012

65. Wheeler J.G., Slack N.F., Dancan A., Whitehead P.J., Russell G., Harvey R.F. The diagnosis of intraabdominal abscesses in patients with severe Crohn’s disease. The Quarterly journal of medicine. 1992;82(298):159–167.

66. Seyedian S.S., Nokhostin F., Malamir M.D. A review of the diagnosis, prevention, and treatment methods of inflammatory bowel disease. Journal of medicine and life. 2019;12(2):113–122. DOI: 10.25122/jml-2018-0075

67. Mamieva Z.A., Poluektova E.A., Shifrin O.S. New possibilities for the treatment of crohn’s disease. Russian Journal of Gastroenterology, Hepatology, Coloproctology = Rossiiskii zhurnal gastroenterologii, gepatologii, koloproktologii. 2019;29(5):13–20 (In Russ.). DOI: 10.22416/1382-43762019-29-5-13-20

68. Harris K.A., Horst S., Gadani A., Nohl A., Annis K., Duley C., Beaulieu D., Ghazi L., Schwartz D.A. Patients with refractory Crohn’s disease successfully treated with ustekinumab. Inflammatory bowel diseases. 2016;22(2):397–401. DOI: 10.1097/MIB.0000000000000624

69. Zallot C., Quilliot D., Chevaux J. B., Peyrin-Biroulet C., Guéant-Rodriguez R.M., Freling E., Collet-Fenetrier B., Williet N., Ziegler O., Bigard M-A., Guéant J-L., Peyrin-Biroulet L. Dietary beliefs and behavior among inflammatory bowel disease patients. Inflammatory bowel diseases. 2013;19(1):66–72. DOI: 10.1002/ibd.22965

70. Shoda R., Matsueda K., Yamato S., Umeda N. Epidemiologic analysis of Crohn disease in Japan: increased dietary intake of n-6 polyunsaturated fatty acids and animal protein relates to the increased incidence of Crohn disease in Japan. The American Journal of Clinical Nutrition. 1996;63(5):741–745. DOI: 10.1093/ajcn/63.5.741

71. Jantchou P., Morois S., Clavel-Chapelon F., Boutron-Ruault M. C., Carbonnel F. Animal protein intake and risk of inflammatory bowel disease: the E3N prospective study. The American Journal of Gastroenterology. 2010;105(10):2195–2201. DOI: 10.1038/ajg.2010.192

72. Martinez-Medina M., Denizot J., Dreux N., Western diet induces dysbiosis with increased E coli in CEABAC10 mice, alters host barrier function favouring AIEC colonisation. Gut. 2014;63(1):116–124. DOI: 10.1136/gutjnl-2012-304119

73. Hassan A., Ibrahim A., Mbodji K., An α-linolenic acid-rich formula reduces oxidative stress and inflammation by regulating NF-ĸB in rats with TNBS-induced colitis. The Journal of Nutrition. 2010;140(10):1714–1721. DOI: 10.3945/jn.109.119768

74. Paul S., Wand M., Emerick G.T., Richter J.M. The role of latanoprost in an inflammatory bowel disease flare. Gastroenterology report (Oxf). 2014;2(3):232–234. DOI: 10.1093/gastro/gou044

75. Noriega B.S., Sanchez-Gonzalez M.A., Salyakina D., Coffman J. Understanding the impact of omega-3 rich diet on the gut microbiota. Case reports in medicine. 2016;2016:3089303. DOI: 10.1155/2016/3089303

76. Menni C., Zierer J., Pallister T., Jackson M.A., Long T., Mohney R.P., Steves C.J., Spector T.D., Valdes A.M. Omega-3 fatty acids correlate with gut microbiome diversity and production of N-carbamylglutamate in middle aged and elderly women. Scientific reports. 2017;7(1):11079. DOI: 10.1038/s41598-017-10382-2

77. Purasiri P., Murray A., Richardson S., Heys S.D., Horrobin D., Eremin O. Modulation of cytokine production in vivo by dietary essential fatty acids in patients with colorectal cancer. Clinical science. 1994;87(6):711–717. DOI: 10.1042/cs0870711