EXTRA INTESTINAL MANIFESTATIONS AND COMPLICATIONS IN INFLAMMATORY BOWEL DISEASE
Abstract
Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), doesn't affect only the intestinal tract, but also involve other organs such as: eyes, skin, joints, liver and biliary tracts, kidneys, lungs, vascular system. It is difficult to differentiate the true extraintestinal manifestations from secondary extraintestinal complications. The pathogenetic autoimmune mechanisms include genetic susceptibility, antigenic display of autoantigen, aberrant self-recognition and immuno-pathogenetic autoantibodies against organ-specific cellular antigens shared by colon and extra-colonic organs. An important role is owned by microbes due to molecular mimicry. This paper reviews the frequency, clinical presentation and therapeutic implications of extraintestinal symptoms in inflammatory bowel diseases.
References
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20. Tavarela VF. Review article: skin complications associated with inflammatory bowel disease. Aliment Pharmacol Ther 2004; 20 Suppl 4: 50-53.
21. Menachem Y, Gotsman I. Clinical manifestations of pyoderma gangrenosum associated with inflam-matory bowel disease. Isr Med Assoc J 2004; 6: 88-90.
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23. Mintz R, Feller ER, Bahr RL, Shah SA. Ocular manifestations of inflammatory bowel disease. Inflamm Bowel Dis 2004; 10: 135-139.
24. Stocker W, Otte M, Ulrich S, Normann D, Finkbeiner H, Stokker K, Jantschek G, Scriba PC. Auto-immunity to pancreatic juice in Crohn‘s disease. Results of an autoantibody screening in patients with chronic inflammatory bowel disease. Scand J Gastroenterol Suppl 1987; 139: 41-52.
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26. Heikius B, Niemela S, Lehtola J, Karttunen T, Lahde S. Pancreatic duct abnormalities and pancreatic function in patients with chronic inflammatory bowel disease. Scand J Gastroenterol 1996; 31: 517-523.
27. Miehsler W, Reinisch W, Valic E, Osterode W, Tillinger W, Feichtenschlager T, Grisar J, Machold K, Scholz S, Vogelsang H, Novacek G. Is inflammatory bowel disease an independent and disease specific risk factor for thromboembolism? Gut 2004; 53: 542-548.
28. Papa A, De Stefano V, Danese S, Gasbarrini A, Gasbarrini G. Thrombotic complications in inflam-matory bowel disease: a multifactorial etiology. Am J Gastroenterol 2001; 96: 1301-1302.
29. Oldenburg B, Van Tuyl BA, van der Griend R, Fijnheer R, van Berge Henegouwen GP. Risk factors for thromboembolic complications in inflammatory bowel disease: the role of hyperhomocysteinaemia. Dig Dis Sci 2005; 50: 235-240.
30. Gasche C, Lomer MC, Cavill I, Weiss G. Iron, anaemia, and inflammatory bowel diseases. Gut 2004; 53: 1190-1197.
31. Archimandritis AJ, Weetch MS. Kidney granuloma in Crohn’s disease. BMJ 1993; 307: 540-541.
32. Gasche C. Complications of inflammatory bowel disease. Hepatogastroenterol 2000; 47: 49-56.
33. Fernandez-Castroagudin J, Brage Varela A, Lens Neo XM, Martinez Castro J, Abdulkader I. Renal amyloidosis as initial clinical manifestation of Crohn's disease. Gastroenterol Hepatol 2002; 25: 395-397.
34. MacDermott RP, Nash GS, Nahm MH. Antibody secretion by human intestinal mononuclear cells from normal controls and inflammatory bowel disease patients. Immunol Invest 1989; 18: 449–457.
35. Bienenstock J, McDermott M, Befus D, O’Neill M. A common mucosal immunologic system involv-ing the bronchus, breast and bowel. Adv Exp Med Biol 1978; 107: 53–59.
36. Mikhaĭlova ZF, Levchenko SV, Karagodina IuIa, Barinov VV. Pulmonary disorders in patients with chronic inflammatory bowel disease, Eksp Klin Gastroenterol 2011; (3): 54–59.
37. Herrlinger KR, Noftz MK, Dalhoff K, Ludwig D, Stange EF, Fellermann K. Alterations in pulmonary function in inflammatory bowel disease are frequent and persist during remission. Am J Gastroenterol 2002; 97: 377-381.
38. Faller M, Gasser B, Massard G, Pauli G, Quoix E. Pulmonary migratory infiltrates and pachypleuritis in a patient with Crohn’s disease. Respiration 2000; 67: 459–463.
39. Patwardhan RV, Heilpern RJ, Brewster AC, Darrah JJ. Pleuropericarditis: an extraintestinal compli-cation of inflammatory bowel disease. Report of three cases and review of literature. Arch Intern Med 1983; 143: 94–96.
40. Sossai P, Cappellato MG, Stefani S. Can a drug-induced pulmonary hypersensitivity reaction be dose-dependent? A case with mesalamine. Mt Sinai J Med 2001; 68: 389–395.
41. Ananthakrishnan AN, Attila T, Otterson MF, Lipchik RJ, Massey BT, Komorowski RA, Binion DG. Severe pulmonary toxicity after azathioprine/6-mercaptopurine initiation for the treatment of inflam-matory bowel disease. J Clin Gastroenterol 2007; 41: 682–688.
42. Sostman HD, Matthay RA, Putman CE, Smith GJ. Methotrexate-induced pneumonitis. Medicine (Baltimore) 1976; 55: 371–388.
43. Milenković B, Dudvarski-Ilić A, Janković G, Martinović L, Mijac D. Anti-TNF treatment and miliary tuberculosis in Crohn’s disease. Srp Arh Celok Lek 2011; 139: 514–517.
44. Rellecke P, Strauer BE. Chronic inflammatory bowel disease and cardiovascular complications. Med Klin (Munich) 2006; 22(101 Suppl 1): 56-60.
45. Sedwick LA, Klingele TG, Burde RM, Behrens MM. Optic neuritis in inflammatory bowel disease. J Clin Neuroophthalmol 1984; 4: 3-6.
46. Nemni R, Fazio R, Corbo M, Sessa M, Comi G, Canal N. Peripheral neuropathy associated with Crohn’s disease. Neurology 1987; 37: 1414-1417.
47. Akbayir N, Calis AB, Alkim C, Sokmen HM, Erdem L, Ozbal A, Bolukbas F, Akbayir N. Sensori-neural hearing loss in patients with inflammatory bowel disease: a subclinical extraintestinal manifes-tation. Dig Dis Sci 2005; 50: 1938-1945.
48. Kimura K, Hunter SF, Thollander MS, Loftus EV Jr, Melton LJ 3rd, O’Brien PC, Rodriguez M, Phillips SF. Concurrence of inflammatory bowel disease and multiple sclerosis. Mayo Clin Proc 2000; 75: 802-806.
49. Gupta G, Gelfand JM, Lewis JD. Increased risk for demyelinating diseases in patients with inflamma-tory bowel disease. Gastroenterol 2005; 129: 819-826.
50. Langer-Gould A, Atlas SW, Green AJ, Bollen AW, Pelletier D. Progressive multifocal leukoencepha-lopathy in a patient treated with natalizumab. N Engl J Med 2005; 353: 375-381.
2. Bhagat S, Das KM. A shared and unique peptide in the human colon, eye, and joint detected by a monoclonal antibody.Gastroenterology 1994; 107: 103-108.
3. Roussomoustakaki M, Satsangi J, Welsh K, Louis E, Fanning G, Targan S, Landers C, Jewell DP. Genetic markers may predict disease behavior in patients with ulcerative colitis. Gastroenterology 1997; 112: 1845-1853.
4. Orchard TR, Thiyagaraja S, Welsh KI, Wordsworth BP, Hill Gaston JS, Jewell DP. Clinical phenotype is related to HLA genotype in the peripheral arthropathies of inflammatory bowel disease. Gas-troenterology 2000; 118: 274-278.
5. Chapman RW, Varghese Z, Gaul R, Patel G, Kokinon N, Sherlock S. Association of primary scle-rosing cholangitis with HLA-B8. Gut 1983; 24: 38-41.
6. Peeters H, Vander Cruyssen B, Laukens D, Coucke P, Marichal D, Van Den Berghe M, Cuvelier C, Remaut E, Mielants H, De Keyser F, Vos MD. Radiological sacroiliitis, a hallmark of spondylitis, is linked with CARD15 gene polymorphisms in patients with Crohn's disease. Ann Rheum Dis 2004; 63: 1131-1134.
7. Das KM. Relationship of extraintestinal involvements in inflammatory bowel disease: new insights into autoimmune pathogenesis. Dig Dis Sci 1999; 44: 1-13.
8. Orchard TR, Wordsworth BP, Jewell DP. Peripheral arthropathies in inflammatory bowel disease: their articular distribution distribution and natural history. Gut 1998; 42: 387-391.
9. Orchard TR, Dhar A, Simmons JD, Vaughan R, Welsh KI, Jewell DP. MHC class I chain-like gene A (MICA) and its associations with inflammatory bowel disease and peripheral arthropathy. Clin Exp Immunol 2001; 126: 437-440.
10. Dorofeyev AE, Vasilenko IV, Rassokhina OA. Joint extraintestinal manifestations in ulcerative colitis. Dig Dis 2009; 27(4): 502-510.
11. Salvarani C, Fornaciari G, Beltrami M, Macchioni PL. Musculoskeletal manifestations in inflammatory bowel disease. Eur J Intern Med 2000; 11: 210-214.
12. Mielants H, Veys EM, De Vos M, Cuvelier C, Goemaere S, De Clercq L, Schatteman L, Elewaut D. The evolution of spondyloarthropathies in relation to gut histology. I. Clinical aspects. J Rheumatol 1995; 22: 2266-2272.
13. Vidal NO, Brandstrom H, Jonsson KB, Ohlsson C. Osteoprotegerin mRNA is expressed in primary human osteoblast-like cells: down-regulation by glucocorticoids. J Endocrinol 1998; 159: 191-195.
14. Haderslev KV, Tjellesen L, Sorensen HA, Staun M. Alendronate increases lumbar spine bone mineral density in patients with Crohn's disease. Gastroenterol 2000; 119: 639-646.
15. Compston JE, Horton LW, Laker MF, Ayers AB, Woodhead JS, Bull HJ, Gazet JC, Pilkington TR. Bone disease after jejunoileal bypass for obesity. Lancet 1978; 2: 1-4.
16. Talwalkar JA, Lindor KD. Primary sclerosing cholangitis. Inflamm Bowel Dis 2005; 11: 62-72.
17. Bergquist A, Ekbom A, Olsson R, Kornfeldt D, Loof L, Danielsson A, Hultcrantz R, Lindgren S, Prytz H, Sandberg- Gertzen H, Almer S, Granath F, Broome U. Hepatic and extrahepatic malignancies in primary sclerosing cholangitis. J Hepatol 2002; 36: 321-327.
18. Wiesner RH, Shanahan F. Neutrophil cytoplasmic antibodies: a link between primary sclerosing cholangitis and ulcerative colitis. Gastroenterol 1991; 100: 1385-1391.
19. Schwartz DA, Loftus EV Jr, Tremaine WJ, Panaccione R, Harmsen WS, Zinsmeister AR, Sandborn WJ. The natural history of fistulizing Crohn's disease in Olmsted County, Minnesota. Gastroenterol 2002; 122: 875-880.
20. Tavarela VF. Review article: skin complications associated with inflammatory bowel disease. Aliment Pharmacol Ther 2004; 20 Suppl 4: 50-53.
21. Menachem Y, Gotsman I. Clinical manifestations of pyoderma gangrenosum associated with inflam-matory bowel disease. Isr Med Assoc J 2004; 6: 88-90.
22. Orchard TR, Chua CN, Ahmad T, Cheng H, Welsh KI, Jewell DP. Uveitis and erythema nodosum in inflammatory bowel disease: clinical features and the role of HLA genes. Gastroenterol 2002; 123: 714-718.
23. Mintz R, Feller ER, Bahr RL, Shah SA. Ocular manifestations of inflammatory bowel disease. Inflamm Bowel Dis 2004; 10: 135-139.
24. Stocker W, Otte M, Ulrich S, Normann D, Finkbeiner H, Stokker K, Jantschek G, Scriba PC. Auto-immunity to pancreatic juice in Crohn‘s disease. Results of an autoantibody screening in patients with chronic inflammatory bowel disease. Scand J Gastroenterol Suppl 1987; 139: 41-52.
25. Angelini G, Cavallini G, Bovo P, Brocco G, Castagnini A, Lavarini E, Merigo F, Tallon N, Scuro LA. Pancreatic function in chronic inflammatory bowel disease. Int J Pancreatol 1988; 3: 185-193.
26. Heikius B, Niemela S, Lehtola J, Karttunen T, Lahde S. Pancreatic duct abnormalities and pancreatic function in patients with chronic inflammatory bowel disease. Scand J Gastroenterol 1996; 31: 517-523.
27. Miehsler W, Reinisch W, Valic E, Osterode W, Tillinger W, Feichtenschlager T, Grisar J, Machold K, Scholz S, Vogelsang H, Novacek G. Is inflammatory bowel disease an independent and disease specific risk factor for thromboembolism? Gut 2004; 53: 542-548.
28. Papa A, De Stefano V, Danese S, Gasbarrini A, Gasbarrini G. Thrombotic complications in inflam-matory bowel disease: a multifactorial etiology. Am J Gastroenterol 2001; 96: 1301-1302.
29. Oldenburg B, Van Tuyl BA, van der Griend R, Fijnheer R, van Berge Henegouwen GP. Risk factors for thromboembolic complications in inflammatory bowel disease: the role of hyperhomocysteinaemia. Dig Dis Sci 2005; 50: 235-240.
30. Gasche C, Lomer MC, Cavill I, Weiss G. Iron, anaemia, and inflammatory bowel diseases. Gut 2004; 53: 1190-1197.
31. Archimandritis AJ, Weetch MS. Kidney granuloma in Crohn’s disease. BMJ 1993; 307: 540-541.
32. Gasche C. Complications of inflammatory bowel disease. Hepatogastroenterol 2000; 47: 49-56.
33. Fernandez-Castroagudin J, Brage Varela A, Lens Neo XM, Martinez Castro J, Abdulkader I. Renal amyloidosis as initial clinical manifestation of Crohn's disease. Gastroenterol Hepatol 2002; 25: 395-397.
34. MacDermott RP, Nash GS, Nahm MH. Antibody secretion by human intestinal mononuclear cells from normal controls and inflammatory bowel disease patients. Immunol Invest 1989; 18: 449–457.
35. Bienenstock J, McDermott M, Befus D, O’Neill M. A common mucosal immunologic system involv-ing the bronchus, breast and bowel. Adv Exp Med Biol 1978; 107: 53–59.
36. Mikhaĭlova ZF, Levchenko SV, Karagodina IuIa, Barinov VV. Pulmonary disorders in patients with chronic inflammatory bowel disease, Eksp Klin Gastroenterol 2011; (3): 54–59.
37. Herrlinger KR, Noftz MK, Dalhoff K, Ludwig D, Stange EF, Fellermann K. Alterations in pulmonary function in inflammatory bowel disease are frequent and persist during remission. Am J Gastroenterol 2002; 97: 377-381.
38. Faller M, Gasser B, Massard G, Pauli G, Quoix E. Pulmonary migratory infiltrates and pachypleuritis in a patient with Crohn’s disease. Respiration 2000; 67: 459–463.
39. Patwardhan RV, Heilpern RJ, Brewster AC, Darrah JJ. Pleuropericarditis: an extraintestinal compli-cation of inflammatory bowel disease. Report of three cases and review of literature. Arch Intern Med 1983; 143: 94–96.
40. Sossai P, Cappellato MG, Stefani S. Can a drug-induced pulmonary hypersensitivity reaction be dose-dependent? A case with mesalamine. Mt Sinai J Med 2001; 68: 389–395.
41. Ananthakrishnan AN, Attila T, Otterson MF, Lipchik RJ, Massey BT, Komorowski RA, Binion DG. Severe pulmonary toxicity after azathioprine/6-mercaptopurine initiation for the treatment of inflam-matory bowel disease. J Clin Gastroenterol 2007; 41: 682–688.
42. Sostman HD, Matthay RA, Putman CE, Smith GJ. Methotrexate-induced pneumonitis. Medicine (Baltimore) 1976; 55: 371–388.
43. Milenković B, Dudvarski-Ilić A, Janković G, Martinović L, Mijac D. Anti-TNF treatment and miliary tuberculosis in Crohn’s disease. Srp Arh Celok Lek 2011; 139: 514–517.
44. Rellecke P, Strauer BE. Chronic inflammatory bowel disease and cardiovascular complications. Med Klin (Munich) 2006; 22(101 Suppl 1): 56-60.
45. Sedwick LA, Klingele TG, Burde RM, Behrens MM. Optic neuritis in inflammatory bowel disease. J Clin Neuroophthalmol 1984; 4: 3-6.
46. Nemni R, Fazio R, Corbo M, Sessa M, Comi G, Canal N. Peripheral neuropathy associated with Crohn’s disease. Neurology 1987; 37: 1414-1417.
47. Akbayir N, Calis AB, Alkim C, Sokmen HM, Erdem L, Ozbal A, Bolukbas F, Akbayir N. Sensori-neural hearing loss in patients with inflammatory bowel disease: a subclinical extraintestinal manifes-tation. Dig Dis Sci 2005; 50: 1938-1945.
48. Kimura K, Hunter SF, Thollander MS, Loftus EV Jr, Melton LJ 3rd, O’Brien PC, Rodriguez M, Phillips SF. Concurrence of inflammatory bowel disease and multiple sclerosis. Mayo Clin Proc 2000; 75: 802-806.
49. Gupta G, Gelfand JM, Lewis JD. Increased risk for demyelinating diseases in patients with inflamma-tory bowel disease. Gastroenterol 2005; 129: 819-826.
50. Langer-Gould A, Atlas SW, Green AJ, Bollen AW, Pelletier D. Progressive multifocal leukoencepha-lopathy in a patient treated with natalizumab. N Engl J Med 2005; 353: 375-381.
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