1. Complications in IBD for acute internal medicine S Sebastian

2. Overview IBD and VTE IBD and VTE IBD and C difficile IBD and C difficile IBD & Toxic Megacolon IBD & Toxic Megacolon

3. Case…. 37 yr old female 37 yr old female Pancolitis diagnosed 8 months ago. Pancolitis diagnosed 8 months ago. 1 previous admission needing steroids 1 previous admission needing steroids Further admission with active disease despite oral steroids Further admission with active disease despite oral steroids Bloods Hb 10.2, platelets 590, CRP 89, Alb 26 Bloods Hb 10.2, platelets 590, CRP 89, Alb 26 Started on IV steroids. Started on IV steroids. Day 4- recorded bilateral oedema feet- presumed due to hypoalbuminemia ( albumin 21) Day 4- recorded bilateral oedema feet- presumed due to hypoalbuminemia ( albumin 21) Day 7- acute SOB. CTPA-B/L PE, Doppler- B/L ileo-femoral DVT Day 7- acute SOB. CTPA-B/L PE, Doppler- B/L ileo-femoral DVT

4. VTE in IBD Complication in IBD 0.7 to 7.7 % Complication in IBD 0.7 to 7.7 % Extensive, unusual sites Extensive, unusual sites Increased mortality and morbidity Increased mortality and morbidity

5. VTE in IBD- mechanisms Hyperhomocystinemia Hyperhomocystinemia Active inflammatory state Active inflammatory state 80% have active disease 80% have active disease UC- more in extensive colitis UC- more in extensive colitis Thrombocytosis, platelet function defects Thrombocytosis, platelet function defects Increased procoagulant factors Factor V111 Increased procoagulant factors Factor V111 Increased conventional risk factors Increased conventional risk factors No increase in procoagulant mutations No increase in procoagulant mutations

6. Disease specific risk factor for VTE % with VTE Meishler W et al Gur 2004 OR 3.6 (1.7-7.8)

7. Age-adjusted VTE rates in IBD VTE rate Per 1000 admissions

8. Cumulative risk of VTE

9. VTE Time trend analysis Age adjusted VTE per1000 admissions

10. VTE in IBD Mortality Crohns 1.28 (1.03-1.41) Crohns 1.28 (1.03-1.41) UC 1.52 (1.28-1.79) UC 1.52 (1.28-1.79) Age per 10yrs 2.01 (1.85- 2.17) Age per 10yrs 2.01 (1.85- 2.17) Female vs male 0.93 (0.80-1.03) Female vs male 0.93 (0.80-1.03) Race 1.39 (1.03-1.89) Race 1.39 (1.03-1.89) Teaching vs non- 1.17 (0.98- 1.39) Teaching vs non- 1.17 (0.98- 1.39) Ibd related surgery 4.80 (3.97-5.80) Ibd related surgery 4.80 (3.97-5.80) Previous VTE 2.50 (1.83- 3.43) Previous VTE 2.50 (1.83- 3.43) 0.50.751.0

11. Recommendation…. All IBD patients admitted to hospital should have VTE prophylaxis All IBD patients admitted to hospital should have VTE prophylaxis

12. % Prophylactic heparin - UC UK Median 60% North East 55%, Yorkshire and Humber 75%

13. Heparin in treatment of acute UC Ang Y et al APT 2000

14. IBD and VTE IBD and VTE IBD and C difficile IBD and C difficile IBD & Toxic Megacolon IBD & Toxic Megacolon

15. Case …. 41 yr old Jehovah witness with ileocolonic and perianal Crohn`s disease 41 yr old Jehovah witness with ileocolonic and perianal Crohn`s disease On AZT 150mg- remission for over 2yrs On AZT 150mg- remission for over 2yrs Admitted AAU over weekend with 2 day history of profuse diarrhoea with blood,perianal pain Admitted AAU over weekend with 2 day history of profuse diarrhoea with blood,perianal pain Bloods WCC 14, CRP 21, Platelets 408 Bloods WCC 14, CRP 21, Platelets 408 Started on oral steroids, cipro and Metronidazole and discharged Started on oral steroids, cipro and Metronidazole and discharged

16. Case….ctd 5 days later seen in IBD clinic- no improvement 5 days later seen in IBD clinic- no improvement Admitted. Abdo x-ray. Megacolon. No signs of toxicity Admitted. Abdo x-ray. Megacolon. No signs of toxicity Limited sigmoidoscopy- pseudomemebrane Limited sigmoidoscopy- pseudomemebrane Stool C difficile toxin positive Stool C difficile toxin positive Treated with oral Vancomycin. Steroids stopped Treated with oral Vancomycin. Steroids stopped Complete resolution of symptoms Complete resolution of symptoms

17. Infection and Flare up of UC Infections contribute in 14-16% of flare ups of UC Infections contribute in 14-16% of flare ups of UC Steadily increasing concern in IBD patients Steadily increasing concern in IBD patients Retrospective studies- higher C Diff rates than other hospitalized patients Retrospective studies- higher C Diff rates than other hospitalized patients Roderman et al Cli Gastro Hepatol 2007 Issa M et al Clin Gastro Hepatol 2007 Prevalence 39.4/1000 Prevalence 39.4/1000 ? Selection bias ? Selection bias

18. C Difficile in IBD May not have clear history of antibiotic use/hospitalization May not have clear history of antibiotic use/hospitalization Community acquired C diff does not have a better prognosis Community acquired C diff does not have a better prognosis Risk of toxic megacolon 2-3% Risk of toxic megacolon 2-3% No evidence @present for increase in hypervirulent strain in IBD cohort No evidence @present for increase in hypervirulent strain in IBD cohort Predictors of higher risk Predictors of higher risk Females Females Colonic involvement Colonic involvement Winter and spring months Winter and spring months Multiple immunomodulators Multiple immunomodulators

19. National survey (US) of C difficile Prevalence UC 37.3/1000 Crohns 10.9/1000 Non IBD 4.8/1000 Incidence doubled in 7yrs Greater Mortality in UC (OR 3.79, CI 2.84-5.06) but not in Crohn`s (OR 1.66, CI 0.75- 3.66) 45-65% increase in duration of stay and costs Nguyen et al Am J Gastro 2008

20. Increased mortality with co-infection Nationwide in patient sample Nationwide in patient sample 2804 with UC & C Diff 2804 with UC & C Diff 44,400 with C Diff 44,400 with C Diff 77,366 with IBD alone 77,366 with IBD alone IBD 4 times higher mortality than IBD alone (aOR 4.7, 2.9-7.9) or C Diff alone (aOR 2.2 (1.4-3.4) IBD 4 times higher mortality than IBD alone (aOR 4.7, 2.9-7.9) or C Diff alone (aOR 2.2 (1.4-3.4) Stayed 3 days longer Stayed 3 days longer Mortality, surgery rates, endoscopy all higher in UC Mortality, surgery rates, endoscopy all higher in UC Ananthankrishnan et al Gut 2008

21. Recommendation… All patients needing admission for flare up should have stool C difficile and Stool cultures in the work up algorithm All patients needing admission for flare up should have stool C difficile and Stool cultures in the work up algorithm If C diff negative may need to recheck again if lack of response to treatment If C diff negative may need to recheck again if lack of response to treatment

22. IBD audit-Stool Culture & CDT UK Median 45% North East 25%, Yorkshire and Humber 45%

23. IBD and VTE IBD and VTE IBD and C difficile IBD and C difficile IBD & Toxic Megacolon IBD & Toxic Megacolon

24. Case …. 47 yr old with known pancolitis on oral mesalazine 47 yr old with known pancolitis on oral mesalazine Admitted via AAU for uncontrolled flare up despite oral steroids Admitted via AAU for uncontrolled flare up despite oral steroids Stools > 10/day, Blood+++, abdominal pain Stools > 10/day, Blood+++, abdominal pain CP 113, WCC 16,Platelets 497, Alb 27, K 2.9 CP 113, WCC 16,Platelets 497, Alb 27, K 2.9 Started on IV steroids Started on IV steroids

25. Case …ctd 24hrs later- Diarrhoea settled but increasing pain 24hrs later- Diarrhoea settled but increasing pain Gastro and Surgical review Gastro and Surgical review Repeat AXR Repeat AXR

26. What is toxic megacolon? Non obstructive colonic dilatation in the presence of toxic colitis Non obstructive colonic dilatation in the presence of toxic colitis Jalan Criteria Jalan Criteria Radiographic evidence of colonic dilatation ( Transverse >6cm) Radiographic evidence of colonic dilatation ( Transverse >6cm) 3 of 4: Fever, tachycardia, anaemia, leucocytosis 3 of 4: Fever, tachycardia, anaemia, leucocytosis 1 of : hypotension, altered mentation, electrolyte imbalance 1 of : hypotension, altered mentation, electrolyte imbalance Not exclusive to UC but can occur with infective, ischemic or radiation colitis Not exclusive to UC but can occur with infective, ischemic or radiation colitis

27. Toxic megacolon in IBD Lifetime risk in UC- 1-2.5% Lifetime risk in UC- 1-2.5% 2-5% of severe attacks of UC needing admission develop megacolon. 2-5% of severe attacks of UC needing admission develop megacolon. Risk factors Risk factors Extensive active disease Extensive active disease Abrupt discontinuation of steroids/5-ASA Abrupt discontinuation of steroids/5-ASA Use of loperamide, anticholinergics, opiates Use of loperamide, anticholinergics, opiates Hypokalemia particularly after steroids Hypokalemia particularly after steroids

28. Toxic megacolon in IBD…. Perforation leads to mortality up to 20% Perforation leads to mortality up to 20% Signs of peritonism may be masked by steroids Signs of peritonism may be masked by steroids Suspect micro perforation of increasing pain Suspect micro perforation of increasing pain Serial x-rays Serial x-rays Liaise with/ transfer care to gastroenterology and surgery Liaise with/ transfer care to gastroenterology and surgery

29. Summary…. IBD and VTE IBD and VTE IBD and C difficile IBD and C difficile IBD & Toxic Megacolon IBD & Toxic Megacolon Beware of complications in admitted colitics Beware of complications in admitted colitics Seek early (within 24hrs) gastroenterology opinion Seek early (within 24hrs) gastroenterology opinion