# Post-Infectious IBS Robin Spiller



## eric (Jul 8, 1999)

Post-Infectious IBSProfessor Robin Spiller, Wolfson Digestive Diseases CentreUniversity Hospital, Nottingham, NG7 2UH, UKDefinitionWe have defined Post infectious IBS (1) as acute onset Rome II criteria positiveIBS developing after an infectious illness characterised by two or more of thefollowing; fever, vomiting, acute diarrhoea, positive stool culture. Post infectiveIBS is of particular interest because it is â€œnatureâ€™s experimentâ€. Unlike mostother IBS there is a clearly defined start date, and the condition is morehomogenous, being mostly D-IBS.EpidemiologyThere have been at least 5 prospective studies of patients with culture positiveinfective gastroenteritis showing that 7 -31% progress to develop post infectiveIBS (PI-IBS) when assessed 3-6 months after infection (Table 1). Whencompared with uninfected controls two studies have shown an increased risk ofdeveloping IBS OR = 10.1, 95% CI = 3.32-30.69 (2;3).Risk factors for developing PI-IBSThe strongest risk factor for developing PI-IBS is the duration of initial illness.Those with an initial illness lasting >21 days were 11.4(2.2-56) [mean (95% CI)]times more likely to get PI-IBS than someone whose illness was < 7 days.Females were also more at risk than males (RR 3.4(1.1-9.5) while those over 65years were at reduced risk (RR 0.36(0.1-0.9) (4). Gwee also found females atgreater risk (RR 2.5) but when Hypochondriasis was controlled for the gendereffect was no longer significant (5). Later studies also found that when depressionand anxiety were controlled for female sex was no longer a significant factor (6)suggesting it is merely a confounder acting via the known greater incidence ofsuch adverse psychological factors in females. Adverse life events also increasethe risk of PI-IBS (RR 2.0(1.7-2.4) (5). When just a single organism is consideredthen bacterial toxicity appears important with a RR of 10.5(1.4-76) of developingpersistent bowel dysfunction after C. jejuni infection if the bacteria producedelongation of HEp2 cells in culture (7).Clinical FeaturesThe clinical features fit the D-IBS subtype of IBS with pain, loose stools, urgency,bloating and mucus per rectum all significantly increased(5). A 5 year follow upstudy showed recovery to normal bowel habit in only 40% overall and none ofthose with chronic psychiatric disease (8).Pathophysiological Changes Following InfectionThese include an immediate acceleration of transit (5) and development of rectalhypersensitivity. Small intestinal permeability is also increased in virtually allindividuals, however in those who develop PI-IBS, this abnormality persists foryears(9). Following Campylobacter jejuni enteritis there is a universal rise inmucosal inflammatory cells including T lymphocytes (CD4+ and CD8+),calprotectin positive macrophages (CD68+ve) and enteroendocrine cells. Thesechanges, which were seen in nearly all individuals at two weeks, started tosubsided but remained abnormal even at 12 weeks (9). The increased risk of PIIBSwith evidence of greater inflammatory changes has been shown by twoauthors Gwee (5) and Dunlop (6). A recent study from China also confirms thesefindings (10), which were however found both in PI-IBS and D- IBS without anobvious infective precipitant. Lymphocytosis was noted in this study, not only inthe rectum, but also throughout the colon and the terminal ileum, where mastcells were also increased. Mucosal lymphocytosis is likely to be associated withincreased mucosal inflammatory cytokines and increased levels of interleukin-1Î²mRNA as have been demonstrated in PI-IBS, both during infection and 3 monthsafterwards (10;11).Enteroendocrine cell (EC) hyperplasia is also a feature noted after Campylobacterenteritis with an approximately 25% increase in EC cell numbers in those whodevelop PI-IBS compared with infected controls who did not develop IBS (6).Evidence of altered serotonin bioavailabilitySeveral studies have indicated increased release in D-IBS (12) (13) (14). Anenhanced release of 5HT was seen in 15 PI-IBS patients compared with 15constipated IBS and 15 healthy controls (13).Role of Mast CellsAlthough mast cells are not increased in rectal biopsies of PI-IBS they areincreased in terminal ileal biopsies (10). Furthermore, biopsies of the descendingcolon in IBS have been shown to release more histamine and mast celltryptase(15), agents which are known to excite afferent nerves.Effect of inflammation on serotonin transporterIncreased plasma levels of 5HT might be due not to increased release but toimpaired clearance. One recent study (16) has shown reduced mucosalimmunostaining for SERT and reduced mRNA in colonic biopsies from both D-IBSand constipated IBS, similar to that seen in ulcerative colitis. Animal studiessuggest than inflammation can impair expression of SERT which might underliesome cases of PI-IBS.Reference List1. Dunlop SP, Jenkins D, Spiller RC. Distinctive clinical, psychological, andhistological features of postinfective irritable bowel syndrome. Am.JGastroenterol. 2003;98(7):1578-83.2. Parry SD, Stansfield R, Jelley D, Gregory W, Phillips E, Barton JR et al.Does bacterial gastroenteritis predispose people to functionalgastrointestinal disorders? A prospective, community-based, case-controlstudy. Am.J Gastroenterol. 2003;98(9):1970-5.3. Rodriguez LA, Ruigomez A. Increased risk of irritable bowel syndrome afterbacterial gastroenteritis: cohort study. Br.Med.J. 1999;318(7183):565-6.4. Neal KR, Hebden J, Spiller R. Prevalence of gastrointestinal symptoms sixmonths after bacterial gastroenteritis and risk factors for development ofthe irritable bowel syndrome: postal survey of patients. Br.Med.J.1997;314(7083):779-82.5. Gwee KA, Leong YL, Graham C, McKendrick MW, Collins SM, Walters SJ etal. The role of psychological and biological factors in postinfective gutdysfunction. Gut 1999;44(3):400-6.6. Dunlop SP, Jenkins D, Neal KR, Spiller RC. Relative importance ofenterochromaffin cell hyperplasia, anxiety, and depression inpostinfectious IBS. Gastroenterology 2003;125(6):1651-9.7. Thornley JP, Jenkins D, Neal K, Wright T, Brough J, Spiller RC. Relationshipof Campylobacter toxigenicity in vitro to the development of postinfectiousirritable bowel syndrome. J Infect.Dis. 2001;184(5):606-9.8. Neal KR, Barker L, Spiller RC. Prognosis in post-infective irritable bowelsyndrome: a six year follow up study. Gut 2002;51(3):410-3.9. Spiller RC, Jenkins D, Thornley JP, Hebden JM, Wright T, Skinner M et al.Increased rectal mucosal enteroendocrine cells, T lymphocytes, andincreased gut permeability following acute Campylobacter enteritis and inpost-dysenteric irritable bowel syndrome. Gut 2000;47(6):804-11.10. Wang LH, Fang XC, Pan GZ. Bacillary dysentery as a causative factor ofirritable bowel syndrome and its pathogenesis. Gut 2004;53(8):1096-101.11. Gwee KA, Collins SM, Read NW, Rajnakova A, Deng Y, Graham JC et al.Increased rectal mucosal expression of interleukin 1beta in recentlyacquired post-infectious irritable bowel syndrome. Gut 2003;52(4):523-6.12. Bearcroft CP, Perrett D, Farthing MJ. Postprandial plasma 5-hydroxytryptamine in diarrhoea predominant irritable bowel syndrome: apilot study. Gut 1998;42(1):42-6.13. Dunlop SP, Coleman N, Perkins AC, Singh G, Marsden CA, Spiller RC.Abnormalities of 5-hydroxytryptamine metabolism in Irritable BowelSyndrome. Clinical Gastroenterology and Hepatology 2005;3:in press.14. Atkinson W, Lockhart SJ, Keevil BG, Whorwell PJ, Houghton LA. Plateletdepleted plasma 5-hydroxytryptamine (PDP 5-HT) concentrationifference between patients with constipation and diarrhoea predominantirritbale bowel syndrome (IBS). Gastroenterology 2004;126(Suppl 2):A-93.15. Barbara G, Stanghellini V, De Giorgio R, Cremon C, Cottrell GS, Santini Det al. Activated mast cells in proximity to colonic nerves correlate withabdominal pain in irritable bowel syndrome. Gastroenterology2004;126(3):693-702.16. Coates MD, Mahoney CR, Linden DR, Sampson JE, Chen J, Blaszyk H et al.Molecular defects in mucosal serotonin content and decreased serotoninreuptake transporter in ulcerative colitis and irritable bowel syndrome.Gastroenterology 2004;126(7):1657-64.17. Gwee KA, Graham JC, McKendrick MW, Collins SM, Marshall JS, Walters SJet al. Psychometric scores and persistence of irritable bowel afterinfectious diarrhoea. Lancet 1996;347:150-3.18. Parry SD, Barton JR, Welfare MR. Does infectious diarrhoea (ID)predispose people to functional gastro-intestinal disorders (FGIDs)? Aprospective community case-control study. Gut 2002;50:A1.19. Ji S, Park H, Lee D, Song YK, Choi JP, Lee SI. Post-infectious irritablebowel syndrome in patients with Shigella infection. JGastroenterol.Hepatol. 2005;20(3):381-6.Table 1Incidence of Post infectious IBS after culture positive gastroenteritisAuthor(Reference)Year N Percentdeveloping IBSCommentGwee et al(17)1996 75 31% Hospitalised patientswith infectivegastroenteritisNeal et al(4)1997 390 7% Community casesThornley etal (7)2001 180 9% Community casesCampylobacterinfectionDunlop etal (6)2003 747 13% Community casesCampylobacterenteritisParry et al(18)2002 500 cases705 controls16% v 1.9% Community casesCase control designJi et al (19) 2005 101 cases102 controls7% v 0% Salmonella outbreakCase control designhttp://www.ddw.org/user-assets/documents/P...ler.pdf#search='spiller%20and%20ibs'


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