Skip to main content

Advertisement

SpringerLink
Log in

Diagnosis and Therapeutic Management of Extra-Intestinal Manifestations of Inflammatory Bowel Disease

  • Review Article
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Extra-intestinal manifestations (EIMs) are reported frequently in patients with inflammatory bowel disease (IBD) and may be diagnosed before, concurrently or after the diagnosis of IBD. EIMs in IBD may be classified based on their association with IBD disease activity. The first group has a direct relationship with the activity of the bowel disease and includes pauciarticular arthritis, oral aphthous ulcers, erythema nodosum and episcleritis. The second group of EIMs appears to follow an independent course from the underlying bowel disease activity and include ankylosing spondylitis and uveitis. The third group includes EIMs that may or may not be related to intestinal inflammation, such as pyoderma gangrenosum and probably primary sclerosing cholangitis (PSC). Genetic susceptibility, aberrant self-recognition and immunopathogenic autoantibodies against organ-specific cellular antigens shared by the colon and extra-colonic organs may contribute to the pathogenesis and development of these EIMs. The use of biological agents in the IBD armamentarium has expanded the treatment options for some of the disabling EIMs and these agents form the cornerstone in managing most of the disabling EIMs. PSC is one of the most common hepatobiliary manifestations associated with IBD in which no clear treatment options exist other than endoscopic therapy and liver transplantation. Future research targeting the pathogenesis, early diagnosis and treatment of these EIMs is required.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Bernstein CN, Blanchard JF, Rawsthorne P, et al. The prevalence of extraintestinal diseases in inflammatory bowel disease: a population-based study. Am J Gastroenterol 2001; 96(4): 1116–22

    Article  PubMed  CAS  Google Scholar 

  2. Ricart E, Panaccione R, Loftus Jr EV, et al. Autoimmune disorders and extraintestinal manifestations in first-degree familial and sporadic inflammatory bowel disease: a case-control study. Inflamm Bowel Dis 2004; 10(3): 207–14

    Article  PubMed  Google Scholar 

  3. Bernstein CN, Wajda A, Blanchard JF. The clustering of other chronic inflammatory diseases in inflammatory bowel disease: a population-based study. Gastro-enterology 2005; 129(3): 827–36

    Article  Google Scholar 

  4. Mendoza JL, Lana R, Taxonera C, et al. Extraintestinal manifestations in inflammatory bowel disease: differences between Crohn’s disease and ulcerative colitis [in Spanish]. Med Clin (Barc) 2005; 125(8): 297–300

    Article  Google Scholar 

  5. Monsén U, Sorstad J, Hellers G, et al. Extracolonic diagnoses in ulcerative colitis: an epidemiological study. Am J Gastroenterol 1990; 85(6): 711–6

    PubMed  Google Scholar 

  6. Loftus Jr EV. Management of extraintestinal manifestations and other complications of inflammatory bowel disease. Curr Gastroenterol Rep 2004; 6(6): 506–13

    Article  PubMed  Google Scholar 

  7. Rothfuss KS, Stange EF, Herrlinger KR. Extraintestinal manifestations and complications in inflammatory bowel diseases. World J Gastroenterol 2006; 12(30): 4819–31

    PubMed  CAS  Google Scholar 

  8. Levine JS, Burakoff R. Extraintestinal manifestations of inflammatory bowel disease. Gastroenterol Hepatol (N Y) 2011 Apr; 7(4): 235–41

    Google Scholar 

  9. Navaneethan U, Shen B. Hepatopancreatobiliary manifestations and complications associated with inflammatory bowel disease. Inflamm Bowel Dis 2010; 16(9): 1598–619

    Article  PubMed  Google Scholar 

  10. Orchard TR, Chua CN, Ahmad T, et al. Uveitis and erythema nodosum in inflammatory bowel disease: clinical features and the role of HLA genes. Gastroenterology 2002; 123(3): 714–8

    Article  PubMed  Google Scholar 

  11. Chapman RW, Cottone M, Selby WS, et al. Serum auto-antibodies, ulcerative colitis and primary sclerosing cholangitis. Gut 1986; 27(1): 86–91

    Article  PubMed  CAS  Google Scholar 

  12. Geng X, Biancone L, Dai HH, et al. Tropomyosin isoforms in intestinal mucosa: production of autoantibodies to tropomyosin isoforms in ulcerative colitis. Gastroenterology 1998; 114(5): 912–22

    Article  PubMed  CAS  Google Scholar 

  13. Satsangi J, Grootscholten C, Holt H, et al. Clinical patterns of familial inflammatory bowel disease. Gut 1996; 38(5): 738–41

    Article  PubMed  CAS  Google Scholar 

  14. Roussomoustakaki M, Satsangi J, Welsh K, et al. Genetic markers may predict disease behavior in patients with ulcerative colitis. Gastroenterology 1997; 112(6): 1845–53

    Article  PubMed  CAS  Google Scholar 

  15. Orchard TR, Thiyagaraja S, Welsh KI, et al. Clinical phenotype is related to HLA genotype in the peripheral arthropathies of inflammatory bowel disease. Gastroenterology 2000; 118(2): 274–8

    Article  PubMed  CAS  Google Scholar 

  16. Chapman RW, Varghese Z, Gaul R, et al. Association of primary sclerosing cholangitis with HLA-B8. Gut 1983; 24(1): 38–41

    Article  PubMed  CAS  Google Scholar 

  17. Veloso FT, Carvalho J, Magro F. Immune-related systemic manifestations of inflammatory bowel disease: a prospective study of 792 patients. J Clin Gastroenterol 1996; 23(1): 29–34

    Article  PubMed  CAS  Google Scholar 

  18. Ardizzone S, Puttini PS, Cassinotti A, et al. Extraintestinal manifestations of inflammatory bowel disease. Dig Liver Dis 2008; 40 Suppl. 2: S253–9

    Article  PubMed  Google Scholar 

  19. Bargiggia S, Maconi G, Elli M, et al. Sonographic prevalence of liver steatosis and biliary tract stones in patients with inflammatory bowel disease: study of 511 subjects at a single center. J Clin Gastroenterol 2003; 36(5): 417–20

    Article  PubMed  Google Scholar 

  20. Herrlinger KR, Noftz MK, Dalhoff K, et al. Alterations in pulmonary function in inflammatory bowel disease are frequent and persist during remission. Am J Gastroenterol 2002; 97(2): 377–81

    Article  PubMed  CAS  Google Scholar 

  21. Black H, Mendoza M, Murin S. Thoracic manifestations of inflammatory bowel disease. Chest 2007; 131(2): 524–32

    Article  PubMed  Google Scholar 

  22. Agrawal M, Arora S, Li J, et al. Bone, inflammation, and inflammatory bowel disease. Curr Osteoporos Rep 2011; 9(4): 251–7

    Article  PubMed  Google Scholar 

  23. American Gastroenterological Association medical position statement: guidelines on osteoporosis in gastrointestinal diseases. Gastroenterology 2003; 124(3): 791–4

    Google Scholar 

  24. Orchard TR, Wordsworth BP, Jewell DP. Peripheral arthropathies in inflammatory bowel disease: their articular distribution and natural history. Gut 1998; 42(3): 387–91

    Article  PubMed  CAS  Google Scholar 

  25. Van den Broek MF, Van de Putte LB, Van den Berg WB. Crohn’s disease associated with arthritis: a possible role for cross-reactivity between gut bacteria and cartilage in the pathogenesis of arthritis. Arthritis Rheum 1988; 31(8): 1077–9

    Article  PubMed  Google Scholar 

  26. Hermann E, Yu DT, Meyer zum Büschenfelde KH, et al. HLA-B27-restricted CD8 T cells derived from synovial fluids of patients with reactive arthritis and ankylosing spondylitis. Lancet 1993; 342(8872): 646–50

    Article  PubMed  CAS  Google Scholar 

  27. Larsen S, Bendtzen K, Nielsen OH. Extraintestinal manifestations of inflammatory bowel disease: epidemiology, diagnosis, and management. Ann Med 2010; 42(2): 97–114

    Article  PubMed  Google Scholar 

  28. Levine JS, Burakoff R. Extraintestinal manifestations of inflammatory bowel disease. Gastroenterol Hepatol (N Y) 2011; 7(4): 235–41

    Google Scholar 

  29. Williams H, Walker D, Orchard TR. Extraintestinal manifestations of inflammatory bowel disease. Curr Gastroenterol Rep 2008; 10(6): 597–605

    Article  PubMed  Google Scholar 

  30. Mahadevan U, Loftus Jr EV, Tremaine WJ, et al. Safety of selective cyclooxygenase-2 inhibitors in inflammatory bowel disease. Am J Gastroenterol 2002; 97(4): 910–4

    Article  PubMed  CAS  Google Scholar 

  31. Reinisch W, Miehsler W, Dejaco C, et al. An open-label trial of the selective cyclo-oxygenase-2 inhibitor, rofecoxib, in inflammatory bowel disease-associated peripheral arthritis and arthralgia. Aliment Pharmacol Ther 2003; 17(11): 1371–80

    Article  PubMed  CAS  Google Scholar 

  32. Biancone L, Tosti C, Geremia A, et al. Rofecoxib and early relapseofinflammatory bowel disease: anopen-labeltrial. Aliment Pharmacol Ther 2004; 19(7): 755–64

    Article  PubMed  CAS  Google Scholar 

  33. Herfarth H, Obermeier F, Andus T, et al. Improvement of arthritis and arthralgia after treatment with infliximab (Remicade) in a German prospective, open-label, multicenter trial in refractory Crohn’s disease. Am J Gastroenterol 2002; 97(10): 2688–90

    Article  PubMed  Google Scholar 

  34. Kaufman I, Caspi D, Yeshurun D, et al. The effect of infliximab on extraintestinal manifestations of Crohn’s disease. Rheumatol Int 2005; 25(6): 406–10

    Article  PubMed  CAS  Google Scholar 

  35. Su CG, Judge TA, Lichtenstein GR. Extraintestinal manifestations of inflammatory bowel disease. Gastroenterol Clin North Am 2002; 31(1): 307–27

    Article  PubMed  Google Scholar 

  36. Fornaciari G, Salvarani C, Beltrami M, et al. Muscoloskeletal manifestations in inflammatory bowel disease. Can J Gastroenterol 2001; 15(6): 399–403

    PubMed  CAS  Google Scholar 

  37. Heuft-Dorenbosch L, Landewé R, Weijers R, et al. Combining information obtained from magnetic resonance imaging and conventional radiographs to detect sacroiliitis in patients with recent onset inflammatory back pain. Ann Rheum Dis 2006; 65(6): 804–8

    Article  PubMed  CAS  Google Scholar 

  38. Leirisalo-Repo M, Turunen U, Stenman S, et al. High frequency of silent inflammatory bowel disease in spondylarthropathy. Arthritis Rheum 1994; 37(1): 23–31

    Article  PubMed  CAS  Google Scholar 

  39. Clegg DO, Reda DJ, Abdellatif M. Comparison of sulfasalazine and placebo for the treatment of axial and peripheral articular manifestations of the seronegative spondylarthropathies: a Department of Veterans Affairs cooperative study. Arthritis Rheum 1999; 42(11): 2325–9

    Article  PubMed  CAS  Google Scholar 

  40. Braun J, Brandt J, Listing J, et al. Treatment of active ankylosing spondylitis with infliximab: a randomised controlled multicentre trial. Lancet 2002; 359(9313): 1187–93

    Article  PubMed  CAS  Google Scholar 

  41. Generini S, Giacomelli R, Fedi R, et al. Infliximab in spondyloarthropathy associated with Crohn’s disease: an open study on the efficacy of inducing and maintaining remission of musculoskeletal and gut manifestations. Ann Rheum Dis 2004; 63(12): 1664–9

    Article  PubMed  CAS  Google Scholar 

  42. van der Heijde D, Kivitz A, Schiff MH, et al. Efficacy and safety of adalimumab in patients with ankylosing spondylitis: results of a multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2006; 54(7): 2136–46

    Article  PubMed  CAS  Google Scholar 

  43. Braun J, Baraliakos X, Listing J, et al. Differences in the incidence of flares or new onset of inflammatory bowel diseases in patients with ankylosing spondylitis exposed to therapy with anti-tumor necrosis factor alpha agents. Arthritis Rheum 2007; 57(4): 639–47

    Article  PubMed  CAS  Google Scholar 

  44. Greenstein AJ, Janowitz HD, Sachar DB. The extraintestinal complications of Crohn’s disease and ulcerative colitis: a study of 700 patients. Medicine (Baltimore) 1976 Sep; 55(5): 401–12

    Article  CAS  Google Scholar 

  45. Huang BL, Chandra S, Shih DQ. Skin manifestations of inflammatory bowel disease. Front Physiol 2012; 3: 13

    PubMed  Google Scholar 

  46. Chiba T, Isomura I, Suzuki A, et al. Topical tacrolimus therapy for pyoderma gangrenosum. J Dermatol 2005; 32(3): 199–203

    PubMed  Google Scholar 

  47. Galun E, Flugelman MY, Rachmilewitz D. Pyoderma gangrenosum complicating ulcerative colitis: successful treatment with methylprednisolone pulse therapy and dapsone. Am J Gastroenterol 1986; 81(10): 988–9

    PubMed  CAS  Google Scholar 

  48. Regueiro M, Valentine J, Plevy S, et al. Infliximab for treatment of pyoderma gangrenosum associated with inflammatory bowel disease. Am J Gastroenterol 2003; 98(8): 1821–6

    Article  PubMed  CAS  Google Scholar 

  49. Brooklyn TN, Dunnill MGS, Shetty A, et al. Infliximab for the treatment of pyoderma gangrenosum: a randomised, double blind, placebo controlled trial. Gut 2006; 55(4): 505–9

    Article  PubMed  CAS  Google Scholar 

  50. Kemmett D, Hunter JA. Sweet’s syndrome: a clinicopathologic review of twenty-nine cases. J Am Acad Dermatol 1990; 23 (3 Pt 1): 503–7

    Article  PubMed  CAS  Google Scholar 

  51. Foster EN, Nguyen KK, Sheikh RA, et al. Crohn’s disease associated with Sweet’s syndrome and Sjögren’s syndrome treated with infliximab. Clin Dev Immunol 2005; 12(2): 145–9

    Article  PubMed  Google Scholar 

  52. Hoffmann RM, Kruis W. Rare extraintestinal manifestations of inflammatory bowel disease. Inflamm Bowel Dis 2004; 10(2): 140–7

    Article  PubMed  CAS  Google Scholar 

  53. Petrelli EA, McKinley M, Troncale FJ. Ocular manifestations of inflammatory bowel disease. Ann Ophthalmol 1982; 14(4): 356–60

    PubMed  CAS  Google Scholar 

  54. Mintz R, Feller ER, Bahr RL, et al. Ocular manifestations of inflammatory bowel disease. Inflamm Bowel Dis 2004; 10(2): 135–9

    Article  PubMed  Google Scholar 

  55. Fries W, Giofré MR, Catanoso M, et al. Treatment of acute uveitis associated with Crohn’s disease and sacroileitis with infliximab. Am J Gastroenterol 2002; 97(2): 499–500

    Article  PubMed  Google Scholar 

  56. Murphy CC, Ayliffe WH, Booth A, et al. Tumor necrosis factor alpha blockade with infliximab for refractory uveitis and scleritis. Ophthalmology 2004; 111(2): 352–6

    Article  PubMed  Google Scholar 

  57. James ER. The etiology of steroid cataract. J Ocul Pharmacol Ther 2007; 23(5): 403–20

    Article  PubMed  CAS  Google Scholar 

  58. Broomé U, Bergquist A. Primary sclerosing cholangitis, inflammatory bowel disease, and colon cancer. Semin Liver Dis 2006; 26(1): 31–41

    Article  PubMed  Google Scholar 

  59. Danese S, Semeraro S, Papa A, et al. Extraintestinal manifestations in inflammatory bowel disease. World J Gastroenterol 2005; 11(46): 7227–36

    PubMed  Google Scholar 

  60. Bergquist A, Ekbom A, Olsson R, et al. Hepatic and extrahepatic malignancies in primary sclerosing cholangitis. J Hepatol 2002; 36(3): 321–7

    Article  PubMed  Google Scholar 

  61. Soetikno RM, Lin OS, Heidenreich PA, et al. Increased risk of colorectal neoplasia in patients with primary sclerosing cholangitis and ulcerative colitis: a meta-analysis. Gastrointest Endosc 2002; 56(1): 48–54

    Article  PubMed  Google Scholar 

  62. Talwalkar JA, Lindor KD. Primary sclerosing cholangitis. Inflamm Bowel Dis 2005; 11(1): 62–72

    Article  PubMed  Google Scholar 

  63. Loftus Jr EV, Harewood GC, Loftus CG, et al. PSC-IBD: a unique form of inflammatory bowel disease associated with primary sclerosing cholangitis. Gut 2005; 54(1): 91–6

    Article  PubMed  Google Scholar 

  64. Penna C, Dozois R, Tremaine W, et al. Pouchitis after ileal pouch-anal anastomosis for ulcerative colitis occurs with increased frequency in patients with associated primary sclerosing cholangitis. Gut 1996; 38(2): 234–9

    Article  PubMed  CAS  Google Scholar 

  65. Navaneethan U, Kochhar G, Venkatesh PGK, et al. Duration and severity of primary sclerosing cholangitis is not associated with risk of neoplastic changes in the colon in patients with ulcerative colitis. Gastrointest Endosc 2012; 75(5): 1045–54.e1

    Article  PubMed  Google Scholar 

  66. Kim WR, Ludwig J, Lindor KD. Variant forms of cholestatic diseases involving small bile ducts in adults. Am J Gastroenterol 2000; 95(5): 1130–8

    Article  PubMed  CAS  Google Scholar 

  67. Pardi DS, Loftus Jr EV, Kremers WK, et al. Ursodeoxycholic acid as a chemopreventive agent in patients with ulcerative colitis and primary sclerosing cholangitis. Gastroenterology 2003; 124(4): 889–93

    Article  PubMed  CAS  Google Scholar 

  68. Harnois DM, Angulo P, Jorgensen RA, et al. High-dose ursodeoxycholic acid as a therapy for patients with primary sclerosing cholangitis. Am J Gastroenterol 2001; 96(5): 1558–62

    Article  PubMed  CAS  Google Scholar 

  69. Lindor KD, Kowdley KV, Luketic VAC, et al. High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis. Hepatology 2009; 50(3): 808–14

    Article  PubMed  CAS  Google Scholar 

  70. Triantos CK, Koukias NM, Nikolopoulou VN, et al. Meta-analysis: ursodeoxycholic acid for primary sclerosing cholangitis. Aliment Pharmacol Ther 2011; 34(8): 901–10

    Article  PubMed  CAS  Google Scholar 

  71. Lindström L, Boberg KM, Wikman O, et al. High dose ursodeoxycholic acid in primary sclerosing cholangitis does not prevent colorectal neoplasia. Aliment Pharmacol Ther 2012; 35(4): 451–7

    Article  PubMed  CAS  Google Scholar 

  72. Eaton JE, Silveira MG, Pardi DS, et al. High-dose ursodeoxycholic acid is associated with the development of colorectal neoplasia in patients with ulcerative colitis and primary sclerosing cholangitis. Am J Gastroenterol 2011; 106(9): 1638–45

    Article  PubMed  CAS  Google Scholar 

  73. Chapman R, Fevery J, Kalloo A, et al. Diagnosis and management of primary sclerosing cholangitis. Hepatology 2010; 51(2): 660–78

    Article  PubMed  CAS  Google Scholar 

  74. Lichtenstein GR, Abreu MT, Cohen R, et al. American Gastroenterological Association Institute medical position statement on corticosteroids, immunomodulators, and infliximab in inflammatory bowel disease. Gastroenterology 2006; 130(3): 935–9

    Article  PubMed  Google Scholar 

  75. Kremer JM, Alarcón GS, Lightfoot Jr RW, et al. Methotrexate for rheumatoid arthritis: suggested guidelines for monitoring liver toxicity. American College of Rheumatology. Arthritis Rheum 1994; 37(3): 316–28

    Article  PubMed  CAS  Google Scholar 

  76. Biancone L, Pavia M, Del Vecchio Blanco G, et al. Hepatitis B and C virus infection in Crohn’s disease. Inflamm Bowel Dis 2001; 7(4): 287–94

    Article  PubMed  CAS  Google Scholar 

  77. Nathan DM, Angus PW, Gibson PR. Hepatitis B and C virus infections and anti-tumor necrosis factor-alpha therapy: guidelines for clinical approach. J Gastroenterol Hepatol 2006; 21(9): 1366–71

    Article  PubMed  CAS  Google Scholar 

  78. Papa A, Mocci G, Bonizzi M, et al. Use of infliximab in particular clinical settings: management based on current evidence. Am J Gastroenterol 2009; 104(6): 1575–86

    Article  PubMed  CAS  Google Scholar 

  79. Siegel CA, Marden SM, Persing SM, et al. Risk of lymphoma associated with combination anti-tumor necrosis factor and immunomodulator therapy for the treatment of Crohn’s disease: a meta-analysis. Clin Gastroenterol Hepatol 2009; 7(8): 874–81

    Article  PubMed  CAS  Google Scholar 

  80. Scherer JR. Inflammatory bowel disease: complications and extraintestinal manifestations. Drugs Today 2009; 45(3): 227–41

    Article  PubMed  CAS  Google Scholar 

  81. Yılmaz A, Demirci NY, Hoşgün D, et al. Pulmonary involvement in inflammatory bowel disease. World J Gastroenterol 2010; 16(39): 4952–7

    Article  PubMed  Google Scholar 

  82. Kelly MG, Frizelle FA, Thornley PT, et al. Inflammatory bowel disease and the lung: is there a link between surgery and bronchiectasis? Int J Colorectal Dis 2006; 21(8): 754–7

    Article  PubMed  Google Scholar 

  83. Persson PG, Bernell O, Leijonmarck CE, et al. Survival and cause-specific mortality in inflammatory bowel disease: a population-based cohort study. Gastroenterology 1996; 110(5): 1339–45

    Article  PubMed  CAS  Google Scholar 

  84. Kanazawa H, Yoshikawa J. A case-control study of bronchial asthma associated with ulcerative colitis: role of airway microvascular permeability. Clin Exp Allergy 2005; 35(11): 1432–6

    Article  PubMed  CAS  Google Scholar 

  85. Camus P, Colby TV. The lung in inflammatory bowel disease. Eur Respir J 2000; 15(1): 5–10

    Article  PubMed  CAS  Google Scholar 

  86. Storch I, Rosoff L, Katz S. Sarcoidosis and inflammatory bowel disease. J Clin Gastroenterol 2001; 33(4): 345

    Article  PubMed  CAS  Google Scholar 

  87. Bernstein CN, Blanchard JF, Leslie W, et al. The incidence of fracture among patients with inflammatory bowel disease: a population-based cohort study. Ann Intern Med 2000; 133(10): 795–9

    PubMed  CAS  Google Scholar 

  88. Shen B, Remzi FH, Oikonomou IK, et al. Risk factors for low bone mass in patients with ulcerative colitis following ileal pouch-anal anastomosis. Am J Gastroenterol 2009; 104(3): 639–46

    Article  PubMed  Google Scholar 

  89. Navaneethan U, Shen L, Venkatesh PGK, et al. Influence of ileal pouch anal anastomosis on bone loss in ulcerative colitis patients. J Crohns Colitis 2011; 5(5): 415–22

    Article  PubMed  Google Scholar 

  90. Kornbluth A, Hayes M, Feldman S, et al. Do guidelines matter? Implementation of the ACG and AGA osteoporosis screening guidelines in inflammatory bowel disease (IBD) patients who meet the guidelines’ criteria. Am J Gastroenterol 2006; 101(7): 1546–50

    Article  PubMed  Google Scholar 

  91. Reffitt DM, Meenan J, Sanderson JD, et al. Bone density improves with disease remission in patients with inflammatory bowel disease. Eur J Gastroenterol Hepatol 2003; 15(12): 1267–73

    Article  PubMed  Google Scholar 

  92. Vogelsang H, Ferenci P, Resch H, et al. Prevention of bone mineral loss in patients with Crohn’s disease by long-term oral vitamin D supplementation. Eur J Gastroenterol Hepatol 1995; 7(7): 609–14

    PubMed  CAS  Google Scholar 

  93. Bartram SA, Peaston RT, Rawlings DJ, et al. A randomized controlled trial of calcium with vitamin D, alone or in combination with intravenous pamidronate, for the treatment of low bone mineral density associated with Crohn’s disease. Aliment Pharmacol Ther 2003; 18(11–12): 1121–7

    Article  PubMed  CAS  Google Scholar 

  94. Haderslev KV, Tjellesen L, Sorensen HA, et al. Alendronate increases lumbar spine bone mineral density in patients with Crohn’s disease. Gastroenterology 2000; 119(3): 639–46

    Article  PubMed  CAS  Google Scholar 

  95. Henderson S, Hoffman N, Prince R. A double-blind placebo-controlled study of the effects of the bisphosphonate risedronate on bone mass in patients with inflammatory bowel disease. Am J Gastroenterol 2006; 101(1): 119–23

    Article  PubMed  CAS  Google Scholar 

  96. Pazianas M, Rhim AD, Weinberg AM, et al. The effect of anti-TNF-alpha therapy on spinal bone mineral density in patients with Crohn’s disease. Ann N Y Acad Sci 2006; 1068: 543–56

    Article  PubMed  CAS  Google Scholar 

  97. Oikonomou K, Kapsoritakis A, Eleftheriadis T, et al. Renal manifestations and complications of inflammatory bowel disease. Inflamm Bowel Dis 2011; 17(4): 1034–45

    Article  PubMed  Google Scholar 

  98. Pardi DS, Tremaine WJ, Sandborn WJ, et al. Renal and urologic complications of inflammatory bowel disease. Am J Gastroenterol 1998; 93(4): 504–14

    Article  PubMed  CAS  Google Scholar 

  99. Jose FA, Garnett EA, Vittinghoff E, et al. Development of extraintestinal manifestations in pediatric patients with inflammatory bowel disease. Inflamm Bowel Dis 2009; 15(1): 63–8

    Article  PubMed  Google Scholar 

  100. McConnell N, Campbell S, Gillanders I, et al. Risk factors for developing renal stones in inflammatory bowel disease. BJU Int 2002; 89(9): 835–41

    Article  PubMed  CAS  Google Scholar 

  101. Greenstein AJ, Sachar DB, Panday AK, et al. Amyloidosis and inflammatory bowel disease: a 50-year experience with 25 patients. Medicine (Baltimore) 1992; 71(5): 261–70

    CAS  Google Scholar 

  102. Wester AL, Vatn MH, Fausa O. Secondary amyloidosis in inflammatory bowel disease: a study of 18 patients admitted to Rikshospitalet University Hospital, Oslo, from 1962 to 1998. Inflamm Bowel Dis 2001; 7(4): 295–300

    Article  PubMed  CAS  Google Scholar 

  103. Singh S, Kumar N, Loftus EV, et al. Neurologic complications in patients with inflammatory bowel disease: increasing relevance in the era of biologics. Inflamm Bowel Dis. Epub 2012 May 2

    Google Scholar 

  104. Oliveira GR, Teles BCV, Brasil ÉF, et al. Peripheral neuropathy and neurological disorders in an unselected Brazilian population-based cohort of IBD patients. Inflamm Bowel Dis 2008; 14(3): 389–95

    Article  PubMed  CAS  Google Scholar 

  105. Sassi SB, Kallel L, Ben Romdhane S, et al. Peripheral neuropathy in inflammatory bowel disease patients: a prospective cohort study. Scand J Gastroenterol 2009; 44(10): 1268–9

    Article  PubMed  Google Scholar 

  106. Gondim FAA, Brannagan TH, Sander HW, et al. Peripheral neuropathy in patients with inflammatory bowel disease. Brain 2005; 128(4): 867–79

    Article  PubMed  CAS  Google Scholar 

  107. Gupta G, Gelfand JM, Lewis JD. Increased risk for demyelinating diseases in patients with inflammatory bowel disease. Gastroenterology 2005; 129(3): 819–26

    Article  PubMed  Google Scholar 

  108. Ha C, Magowan S, Accortt NA, et al. Risk of arterial thrombotic events in inflammatory bowel disease. Am J Gastroenterol 2009; 104(6): 1445–51

    Article  PubMed  Google Scholar 

  109. Gijtenbeek JM, van den Bent MJ, Vecht CJ. Cyclosporine neurotoxicity: a review. J Neurol 1999; 246(5): 339–46

    Article  PubMed  CAS  Google Scholar 

  110. Bloomgren G, Richman S, Hotermans C, et al. Risk of natalizumab-associated progressive multifocal leukoencephalopathy. N Engl J Med 2012; 366(20): 1870–80

    Article  PubMed  CAS  Google Scholar 

  111. Miehsler W, Reinisch W, Valic E, et al. Is inflammatory bowel disease an independent and disease specific risk factor for thromboembolism? Gut 2004; 53(4): 542–8

    Article  PubMed  CAS  Google Scholar 

  112. Nguyen GC, Sam J. Rising prevalence of venous thromboembolism and its impact on mortality among hospitalized inflammatory bowel disease patients. Am J Gastroenterol 2008; 103(9): 2272–80

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine, University of Connecticut Medical Center, Farmington, CT, USA

    Guru Trikudanathan

  2. Department of Internal Medicine, St. Vincents Charity Medical Center, Case Western Reserve University, Cleveland, OH, USA

    Preethi G. K. Venkatesh

  3. The Cleveland Clinic, Digestive Disease Institute, Cleveland, OH, USA

    Udayakumar Navaneethan MD

Authors
  1. Guru Trikudanathan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Preethi G. K. Venkatesh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Udayakumar Navaneethan MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Udayakumar Navaneethan MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Trikudanathan, G., Venkatesh, P.G.K. & Navaneethan, U. Diagnosis and Therapeutic Management of Extra-Intestinal Manifestations of Inflammatory Bowel Disease. Drugs 72, 2333–2349 (2012). https://doi.org/10.2165/11638120-000000000-00000

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/11638120-000000000-00000

Keywords

Search

Navigation