title: Irritable bowel syndrome: a disease still searching for pathogenesis, diagnosis and therapy.
abstract: Irritable bowel syndrome (IBS) is the most frequently diagnosed functional gastrointestinal disorder in primary and secondary care. It is characterised by abdominal discomfort, pain and changes in bowel habits that can have a serious impact on the patient's quality of life. The pathophysiology of IBS is not yet completely clear. Genetic, immune, environmental, inflammatory, neurological and psychological factors, in addition to visceral hypersensitivity, can all play an important role, one that most likely involves the complex interactions between the gut and the brain (gut-brain axis). The diagnosis of IBS can only be made on the basis of the symptoms of the Rome III criteria. Because the probability of organic disease in patients fulfilling the IBS criteria is very low, a careful medical history is critical and should pay particular attention to the possible comorbidities. Nevertheless, the severity of the patient's symptoms or concerns sometimes compels the physician to perform useless and/or expensive diagnostic tests, transforming IBS into a diagnosis of exclusion. The presence of alarming symptoms (fever, weight loss, rectal bleeding, significant changes in blood chemistry), the presence of palpable abdominal masses, any recent onset of symptoms in patient aged over 50 years, the presence of symptoms at night, and a familial history of celiac disease, colorectal cancer and/or inflammatory bowel diseases all warrant investigation. Treatment strategies are based on the nature and severity of the symptoms, the degree of functional impairment of the bowel habits, and the presence of psychosocial disorders. This review examines and discusses the pathophysiological aspects and the diagnostic and therapeutic approaches available for patients with symptoms possibly related to IBS, pointing out controversial issues and the strengths and weaknesses of the current knowledge.
authors.affiliation: Massimo Bellini, Dario Gambaccini, Maria Teresa Urbano, Santino Marchi, Gastrointestinal Unit, Department of Gastroenterology, University of Pisa, 56124 Pisa, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Bellini
authors.affiliation: Massimo Bellini, Dario Gambaccini, Maria Teresa Urbano, Santino Marchi, Gastrointestinal Unit, Department of Gastroenterology, University of Pisa, 56124 Pisa, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Gambaccini
authors.affiliation: Massimo Bellini, Dario Gambaccini, Maria Teresa Urbano, Santino Marchi, Gastrointestinal Unit, Department of Gastroenterology, University of Pisa, 56124 Pisa, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Stasi
authors.affiliation: Massimo Bellini, Dario Gambaccini, Maria Teresa Urbano, Santino Marchi, Gastrointestinal Unit, Department of Gastroenterology, University of Pisa, 56124 Pisa, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Urbano
authors.affiliation: Massimo Bellini, Dario Gambaccini, Maria Teresa Urbano, Santino Marchi, Gastrointestinal Unit, Department of Gastroenterology, University of Pisa, 56124 Pisa, Italy.
authors.forename: Santino
authors.initials: S
authors.lastname: Marchi
authors.affiliation: Massimo Bellini, Dario Gambaccini, Maria Teresa Urbano, Santino Marchi, Gastrointestinal Unit, Department of Gastroenterology, University of Pisa, 56124 Pisa, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Usai-Satta
mesh_terms: D000818:Animals; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000175:diagnosis / Q000209:etiology / Q000628:therapy; D011237:Predictive Value of Tests; D012307:Risk Factors; D012720:Severity of Illness Index; D016896:Treatment Outcome
keywords: Diagnosis; Irritable bowel syndrome; Pathogenesis; Therapy
references.citation: Gastroenterol Hepatol (N Y). 2010 Sep;6(9 Suppl 15):1-12
references.pmid: 22570639
references.citation: BMJ. 2008 Nov 13;337:a2313
references.pmid: 19008265
references.citation: Aliment Pharmacol Ther. 2006 Jul 15;24(2):183-205
references.pmid: 16842448
references.citation: Am J Gastroenterol. 2012 Aug;107(8):1157-63
references.pmid: 22858996
references.citation: Gut. 2007 Dec;56(12):1770-98
references.pmid: 17488783
references.citation: Aliment Pharmacol Ther. 2013 Jun;37(12):1184-97
references.pmid: 23617618
references.citation: Am J Gastroenterol. 2005 Jul;100(7):1550-7
references.pmid: 15984980
references.citation: J Clin Gastroenterol. 2005 Sep;39(8):665-9
references.pmid: 16082273
references.citation: Gastroenterol Clin North Am. 2005 Jun;34(2):305-17
references.pmid: 15862937
references.citation: Aliment Pharmacol Ther. 2007 Jul 15;26(2):237-48
references.pmid: 17593069
references.citation: Gastroenterology. 1991 Jul;101(1):107-15
references.pmid: 2044899
references.citation: Dig Liver Dis. 2003 Sep;35(9):642-7
references.pmid: 14563186
references.citation: Clin Exp Gastroenterol. 2013 Jul 25;6:123-8
references.pmid: 23922505
references.citation: Gastroenterology. 2004 Mar;126(3):693-702
references.pmid: 14988823
references.citation: Am J Gastroenterol. 2003 Jan;98(1):122-7
references.pmid: 12526947
references.citation: Dig Dis Sci. 1998 Feb;43(2):400-11
references.pmid: 9512138
references.citation: Eur J Gastroenterol Hepatol. 1997 Apr;9(4):345-52
references.pmid: 9160196
references.citation: Therap Adv Gastroenterol. 2012 Nov;5(6):387-93
references.pmid: 23152732
references.citation: Gut. 1986 Jan;27(1):37-40
references.pmid: 3949235
references.citation: Scand J Gastroenterol. 2013 Oct;48(10):1127-35
references.pmid: 23957590
references.citation: Am J Gastroenterol. 2005 Jun;100(6):1340-4
references.pmid: 15929767
references.citation: Am J Gastroenterol. 2012 May;107(5):754-60
references.pmid: 22334251
references.citation: Aliment Pharmacol Ther. 2009 Oct;30(7):707-17
references.pmid: 19570102
references.citation: Gastroenterology. 2005 Mar;128(3):574-9
references.pmid: 15765392
references.citation: Aliment Pharmacol Ther. 2009 Feb 1;29(3):329-41
references.pmid: 19006537
references.citation: Gut. 2004 Oct;53(10):1459-64
references.pmid: 15361495
references.citation: World J Gastroenterol. 2012 Apr 14;18(14):1555-64
references.pmid: 22529683
references.citation: Dig Liver Dis. 2006 Feb;38(2):103-8
references.pmid: 16263343
references.citation: Gut. 2010 Mar;59(3):325-32
references.pmid: 19091823
references.citation: Gut. 2003 Jan;52(1):91-3
references.pmid: 12477767
references.citation: Gut. 1998 Jun;42(6):845-9
references.pmid: 9691924
references.citation: Am J Gastroenterol. 2010 Apr;105(4):775-85
references.pmid: 20372130
references.citation: Pain. 2003 May;103(1-2):99-110
references.pmid: 12749964
references.citation: Aliment Pharmacol Ther. 2012 Dec;36(11-12):1009-31
references.pmid: 23066886
references.citation: Gut. 2002 Jul;51 Suppl 1:i29-33
references.pmid: 12077061
references.citation: PLoS One. 2013;8(2):e54831
references.pmid: 23393559
references.citation: Am J Gastroenterol. 2012 Feb;107(2):276-85
references.pmid: 21971535
references.citation: Scand J Gastroenterol Suppl. 1992;192:102-5
references.pmid: 1439559
references.citation: Eur J Surg Suppl. 1998;(583):50-6
references.pmid: 10027673
references.citation: Aliment Pharmacol Ther. 2004 Dec;20(11-12):1253-69
references.pmid: 15606387
references.citation: BMC Gastroenterol. 2012 Oct 24;12:150
references.pmid: 23095376
references.citation: J Int Med Res. 1998 Mar-Apr;26(2):76-81
references.pmid: 9602985
references.citation: Arq Gastroenterol. 2011 Jan-Mar;48(1):36-40
references.pmid: 21537540
references.citation: Gastroenterology. 2013 Aug;145(2):329-38.e1
references.pmid: 23583433
references.citation: Front Pharmacol. 2013 Feb 01;4:7
references.pmid: 23378837
references.citation: Gut. 2003 Dec;52(12):1703-7
references.pmid: 14633946
references.citation: Gastroenterology. 2013 Aug;145(2):320-8.e1-3
references.pmid: 23648697
references.citation: Gastroenterol Clin North Am. 2007 Sep;36(3):665-85, x
references.pmid: 17950443
references.citation: Gastroenterology. 2002 Jun;122(7):1778-83
references.pmid: 12055584
references.citation: Gut. 2013 Jan;62(1):159-76
references.pmid: 22730468
references.citation: Gastroenterology. 2006 Feb;130(2):304-11
references.pmid: 16472586
references.citation: World J Gastroenterol. 2012 Oct 7;18(37):5151-63
references.pmid: 23066308
references.citation: Clin Exp Gastroenterol. 2010;3:127-37
references.pmid: 21694856
references.citation: Am J Gastroenterol. 2012 Feb;107(2):262-72
references.pmid: 22158028
references.citation: Int J Colorectal Dis. 2013 Sep;28(9):1203-8
references.pmid: 23377858
references.citation: J Neurogastroenterol Motil. 2011 Oct;17(4):349-59
references.pmid: 22148103
references.citation: J Gastroenterol. 2012 Nov;47(11):1177-85
references.pmid: 22766747
references.citation: Aliment Pharmacol Ther. 2012 Mar;35(5):587-99
references.pmid: 22251419
references.citation: J Clin Immunol. 2010 Jan;30(1):74-9
references.pmid: 19844779
references.citation: Am J Gastroenterol. 2012 Nov;107(11):1714-24; quiz p.1725
references.pmid: 22986440
references.citation: Scand J Gastroenterol Suppl. 1987;130:77-80
references.pmid: 3306903
references.citation: World J Gastroenterol. 2007 Jan 14;13(2):219-23
references.pmid: 17226899
references.citation: Curr Gastroenterol Rep. 2005 Aug;7(4):264-71
references.pmid: 16042909
references.citation: Aliment Pharmacol Ther. 2006 Jan 1;23(1):191-6
references.pmid: 16393297
references.citation: Clin Gastroenterol. 1985 Jul;14(3):559-73
references.pmid: 3877580
references.citation: Lancet. 2007 May 12;369(9573):1586-8
references.pmid: 17499587
references.citation: Gut. 2006 Dec;55(12):1754-9
references.pmid: 17008364
references.citation: Arch Intern Med. 2000 Jan 24;160(2):221-7
references.pmid: 10647761
references.citation: J Clin Gastroenterol. 2012 May-Jun;46(5):356-66
references.pmid: 22499071
references.citation: Gut. 2006 Oct;55(10):1409-14
references.pmid: 16434428
references.citation: Aliment Pharmacol Ther. 2010 Jul;32(2):144-58
references.pmid: 20412064
references.citation: Curr Gastroenterol Rep. 2013 May;15(5):323
references.pmid: 23580243
references.citation: Gut. 1973 Feb;14(2):125-32
references.pmid: 4696535
references.citation: Therap Adv Gastroenterol. 2012 Jul;5(4):261-8
references.pmid: 22778791
references.citation: Aliment Pharmacol Ther. 2004 Feb 1;19(3):271-9
references.pmid: 14984373
references.citation: World J Gastroenterol. 2011 Dec 14;17(46):5089-96
references.pmid: 22171143
references.citation: Aliment Pharmacol Ther. 2007 Oct 1;26(7):979-86
references.pmid: 17877505
references.citation: Aliment Pharmacol Ther. 2004 Jul;20 Suppl 2:1-9
references.pmid: 15335408
references.citation: Gastroenterology. 2006 Apr;130(5):1480-91
references.pmid: 16678561
references.citation: Gastroenterology. 2002 Apr;122(4):1140-56
references.pmid: 11910364
references.citation: Trials. 2013 Jan 09;14:10
references.pmid: 23302220
references.citation: Am J Gastroenterol. 2007 Dec;102(12):2767-76
references.pmid: 17900326
references.citation: Scand J Gastroenterol. 1997 Sep;32(9):920-4
references.pmid: 9299672
references.citation: Am J Gastroenterol. 2009 Jan;104 Suppl 1:S1-35
references.pmid: 19521341
references.citation: J Nutr. 2012 Aug;142(8):1510-8
references.pmid: 22739368
references.citation: Dig Liver Dis. 2005 Dec;37(12):934-9
references.pmid: 16243592
references.citation: Pharmacoeconomics. 2006;24(1):21-37
references.pmid: 16445300
references.citation: Gastroenterol Clin North Am. 2005 Jun;34(2):281-303
references.pmid: 15862936
references.citation: Gastroenterology. 2011 Oct;141(4):1187-93
references.pmid: 21762658
references.citation: Aliment Pharmacol Ther. 2003 Mar 1;17(5):623-33
references.pmid: 12641510
references.citation: Gastroenterology. 2013 Jan;144(1):218-38
references.pmid: 23261065
references.citation: Aliment Pharmacol Ther. 1997 Apr;11(2):395-402
references.pmid: 9146781
references.citation: Gastroenterology. 2006 Aug;131(2):352-65
references.pmid: 16890589
references.citation: Postgrad Med. 2013 Mar;125(2):40-50
references.pmid: 23816770
references.citation: Am J Gastroenterol. 2009 Feb;104(2):392-400
references.pmid: 19174797
references.citation: Am J Gastroenterol. 2012 Jan;107(1):28-35; quiz 36
references.pmid: 22045120
references.citation: Gut. 2000 Dec;47(6):861-9
references.pmid: 11076888
references.citation: Aliment Pharmacol Ther. 2013 Jan;37(1):49-61
references.pmid: 23116208
references.citation: Gastroenterology. 1996 Feb;110(2):393-404
references.pmid: 8566585
references.citation: N Engl J Med. 2011 Jan 6;364(1):22-32
references.pmid: 21208106
references.citation: JAMA. 1998 Nov 11;280(18):1585-9
references.pmid: 9820260
references.citation: Am J Physiol Gastrointest Liver Physiol. 2012 Oct;303(7):G775-85
references.pmid: 22837345
references.citation: Cochrane Database Syst Rev. 2006 Oct 18;(4):CD005111
references.pmid: 17054239
references.citation: Korean J Intern Med. 2001 Sep;16(3):137-46
references.pmid: 11769571
references.citation: J Pediatr Gastroenterol Nutr. 2009 Apr;48 Suppl 2:S95-7
references.pmid: 19300138
references.citation: Mayo Clin Proc. 1992 Aug;67(8):725-31
references.pmid: 1434910
references.citation: Neurogastroenterol Motil. 2010 Mar;22(3):293-e82
references.pmid: 20025692
references.citation: Gut. 2009 Mar;58(3):367-78
references.pmid: 19001059
references.citation: Scand J Gastroenterol. 2013 Sep;48(9):1048-54
references.pmid: 23883068
references.citation: Gastroenterology. 2002 Dec;123(6):2108-31
references.pmid: 12454866