management of the hospitalized ibd patient...management of the hospitalized uc patient •5-asa...
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Management of the Hospitalized IBD Patient
Drew DuPont MD
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Ulcerative Colitis: Indications for Admission
• Severe ulcerative colitis • Frequent loose bloody stools (≥ 6 per day) • Severe cramps • Systemic toxicity:
• fever • tachycardia (HR ≥ 90) • Anemia (Hgb < 10.5) • Elevated sed rate (ESR ≥ 30)
• Fulminant colitis • > 10 stools/day, continuous bleeding, abdominal pain, distention,
and severe toxic symptoms (fever, anorexia) • Risk of complications (toxic megacolon and perforation)
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Ulcerative Colitis: Evaluation
• Blood work: CBC, LFTs, BMP, CRP, ESR
• Stool studies: C. diff, calprotectin (indirect measurement of fecal leukocytes)
• Abdominal x-ray at presentation and with clinical deterioration • Colonic dilation ≥ 5.5 cm (transverse colon) • Toxic megacolon: colon ≥ 6 cm or cecum ≥ 9 cm and systemic
toxicity
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Management of the Hospitalized UC Patient
• 5-ASA • No RCTs in severe UC • Based on data from trials in milder disease it should be continued • However… if flare coincided with starting or increasing 5-ASA, it
should be discontinued
• Steroids • Methylprednisolone (Solumedrol) 20 mg every 8 hours or 30 mg
every 12 hours • Continuous infusion is not more effective
Bossa F, et al. Am J Gastro 2007;102:601.
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Management of the Hospitalized UC Patient
• Antibiotics • No role in UC without signs of systemic toxicity
• Severe colitis, high fever, leukocytosis with left-shift, and peritoneal signs or megacolon
• Ciprofloxacin & metronidazole
• Bowel rest • not needed if no evidence of fulminant disease
• >10 stools/day, continuous bleeding, abdominal pain, distention, and acute toxic symptoms including fever and anorexia risk of toxic megacolon & perforation
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Management of the Hospitalized UC Patient
• Nutritional support • Enteral nutrition is preferred
• Short-chain fatty acids for colonic epithelial cells
• DVT prophylaxis • IBD is a hypercoagulable state
• Increased risk of DVT & PE in both population-based and hospital-based cohorts
• If no clinical response to IV steroids after 3 days • Endoscopy to rule out CMV (Cytomegalovirus)
• Anti-TNF or cyclosporine
Kappelman MD, et al. Gut 2011; 60:937. Nguyen GC, Sam J. Am J Gastro 2008: 103:2272
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Management of the Hospitalized UC Patient
• Surgery (colectomy) • Fulminant colitis who fail to respond to infliximab or cyclosporine
within 4-7 days • Increase infliximab to 10 mg/kg if severe UC especially when albumin <2.5
• toxic megacolon (diameter ≥6 cm or cecum >9 cm and systemic toxicity) who do not respond to therapy within 72 hours
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Maintenance Therapy in UC
• In patients who respond to IV steroids convert to oral steroid in 3-5 days • Continue prednisone 30-40 mg daily until asymptomatic for 2
weeks
• Taper over 8 weeks • Decrease dose by 5-10 mg a week until down to 20 mg then decrease by
2.5-5 mg per week
• No role in long-term steroids
• Optimize 5-ASA dose
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Management of the Hospitalized Patient with Crohn’s Disease • Moderate to severe Crohn’s disease (CDAI 220-450)
• Failed treatment for mild to moderate disease or patients with prominent symptoms of fever, weight loss, abdominal pain and tenderness, intermittent nausea or vomiting or anemia
• Severe-fulminant disease (CDAI >450) • Persistent symptoms despite steroids or biologic agents as
outpatients or those presenting with high fever, persistent vomiting, intestinal obstruction, significant peritoneal signs, cachexia, or abscess.
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Management of the Hospitalized Patient with Crohn’s Disease • Generally require IV steroids
• Solumedrol 20 mg q 8 hours or 30 mg q 12 hours
• Long-term treatment • Biologic agents and immunomodulators (azathioprine, 6-
mercaptopurine, and methotrexate) • Azathioprine & 6-MP
• TPMT level
• Biologic agents • T-Spot, Hepatitis B surface antigen & antibody, Hepatitis A total antibody, and Hepatitis C
antibody • Abscess: safe to use if on antibiotics
• Role for antibiotics in Crohn’s disease?
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Role of Antibiotics in IBD
• Crohn’s disease: colonic involvement, fistula, perianal disease, abscess • Ciprofloxacin & metronidazole
• Ulcerative colitis: ONLY with fulminant disease
Sutherland L, et al. Gut. 1991;32(9):1071.
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Sutherland L, et al. Gut. 1991;32(9):1071.
Active Crohn’s Disease
Ch
ang
e in
CD
AI
-100
-50
0
50
100
150
Small intestine n=24
Small/large intestine
n=31
Large intestine n=8
Placebo
Metronidazole p=NS
p=.005
p=.05
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Inflammatory Bowel Disease: Does it Matter Where They are Hospitalized? • Improved outcomes in tertiary hospitals with IBD specialists
• More likely to use high-dose biologic therapy (infliximab >5mg/kg)
• Less likely to be on corticosteroids at 30 days
• Surgery more likely to be performed earlier
• Venous thromboembolism (VTE) prophylaxis
• Testing for C. difficile
• Testing for cytomegalovirus (CMV)
Law CC, et al. Inflamm Bowel Dis 2016;22
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Modifiable Risk Factors for Hospital Readmission for IBD at 90 days • 90 day readmission is not associated with disease activity
• For both ulcerative colitis and Crohn’s disease • Anxiety
• Depression
• Chronic pain
• Smoking for Crohn’s disease
Allegretti JR, et al. Inflamm Bowel Dis 2015;21. Barnes EL, et al. Inflamm Bowel Dis 2017;23.
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Venous Thromboembolism (VTE) in IBD
• Risk up to 4 times that of non-IBD
• VTE occurs in 3-5% of IBD patients • 40% in autopsy studies
• Same risk in UC and Crohn’s disease
• Risk in IBD is much higher than other chronic inflammatory diseases • Rheumatoid arthritis & celiac disease
• Only malignancy and heart failure have been shown to have a higher risk
• DVT of the leg & PE most common • also unusual sites: cerebrovascular, portal, mesenteric, retinal veins
Gionchetti P, et al. J Crohn’s and Colitis 2017;135. Tichelaar YI, et al. Tromb Haemost 2012;107. Miehsler W, et al Gut 2004;53.
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Venous Thromboembolism (VTE) in IBD
• Associated with active IBD in 45%-90% • Including non-hospitalized flares
• Higher risk in hospitalized IBD patients • Compared to non-hospitalized IBD patients and
• Hospitalized-non-IBD patients
• Specific risk factors in IBD patients • Fistulizing disease
• Colonic involvement in Crohn’s disease (79% of cases)
• More extensive disease involvement in UC (76% of cases)
• Pregnancy, OCPs, smoking
Bernstein Cn, et al. Thromb Haemost 2001:85. Jackson LM, et al. QJM 1997;90. Nguyen GC, et al. Am J Gastro 2008;103.
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Venous Thromboembolism (VTE) in IBD: Cause of Increased Risk • Active inflammation
• multiple pro-inflammatory cytokines (TNF-α) lead to thrombin generation & downregulation of natural anticoagulant pathways
• IL-6 increases platelet production & reactivity
• Many other coagulation factors involved
• Corticosteroids: independent risk factor
• Nutritional deficiencies
• Hospitalization
• Surgery
van der Poll T, et al. NEJM 1990;322
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Venous Thromboembolism in IBD: Prevention
• Prophylactic anticoagulation! • Low-molecular-weight heparin, unfractionated heparin
• Bleeding risk is not increased
• Prophylaxis recommended for hospitalized moderate-severe IBD flare without severe bleeding • hemodynamic instability (mechanical thromboprophylaxis)
• Most would recommend prophylaxis in IBD patients in remission admitted for other illness
• Prophylaxis in outpatients with a moderate-severe flare if history of VTE • No prophylaxis if outpatient flare without history of VTE
• VTE in IBD patient that occurred not during a flare indefinite anticoagulation
• Increased risk of recurrence in IBD compared to VTE in non-IBD
• Only 35% of gastroenterologists surveyed would give pharmacologic VTE prophylaxis for hospitalized, severe UC Gionchetti P, et al. J Crohn’s and Colitis 2017;135.
Nguyen GC, et al. Gastro 2014; 46. Novacek G, et al. Gastro 2010;139. Tinsley A, et al. J Clin Gastro 2013;47
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CMV in Inflammatory Bowel Disease
• More common in ulcerative colitis than Crohn’s disease • Up to 35% of steroid-refractory UC • Crohn’s disease: T-helper 1 response antiviral effects
• CMV is more common if febrile on admission • 67% vs. 42% in afebrile
• WBC tends to be lower in +CMV
• Corticosteroids associated with CMV (not associated with anti-TNF)
• CMV is associated with longer hospital admissions
• Presence of ulcers is associated with CMV • +PCR and no large (> 5 mm) ulcers responds to conventional therapy
without antiviral therapy
Siciliano RF, et al. Int J Infect Dis 2014;20. Gauss A, et al. Eur J Gastro Hep 2015;27.
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CMV in IBD: diagnosis and treatment
• Occurs as a result of reactivation • Serum IgG is always positive
• Should be ruled out before escalation of immunosuppression • tissue DNA PCR, immunohistochemistry, H&E • CMV antigen
• Sensitivity 60-100% Specificity 83-100% • Doesn’t differentiate between active disease and latent infection and • no association with virus reactivation in the intestinal mucosa
• Most recommend to treat in IBD flare with +CMV • decreased mortality and need for surgery • some studies have shown no effect on disease course
• Do not need to stop immunosuppression unless severe systemic CMV infection
• Ganciclovir iv
• Valganciclovir 900 mg orally twice a day x 2-3 weeks
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Clostridium difficile in IBD
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Clostridium difficile in IBD • C. difficile infection (CDI) doubled in recent years
• Hypervirulent strain (NAP1/B1/027) • increased severity & transmissibility
• Also better methods for diagnosis (ELISA vs. PCR)
• Also doubled in Crohn’s disease and tripled in UC • 3 times higher risk in IBD • Risk of CDI: UC > Crohn’s disease (91% of CDI in IBD have colitis)
• Up to 20% of IBD flares associated with +testing for C. diff • Most studies 5-7% • 19% +CDI in relapsing IBD • 10% of cases of pouchitis
• Higher rate of recurrence and higher mortality in IBD
• Many risk factors: • Hospitalizations (most community-acquired), ppi, corticosteroids, hypoalbuminemia, dysbiosis, antibiotics • Antibiotics in the month before flare in 90% of CDI-IBD vs. 22% of IBD flare neg CDI • Anti-TNF agents have not been associated with increased risk of CDI
• Asymptomatic carriage increased in IBD • 8% vs. 1% • don’t treat generally
McDonald LC, et al. Infect Dis 2006;12 McDonald LC, et al. NEJM 2005;353 Maharshak N, et al. Medicine 2018;97 Issa M, et al. Clin Gastro Hep 2007;5 Meyer AM, et al. J Clin Gastro 2004;38
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Issa M, et al. Clin Gastro Hep 2007;5
Pseudomembranes in 50-60% of non-IBD vs. 0-10% in IBD
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Treatment of CDI in IBD
• No clear guidelines
• 50% failure rate with metronidazole
• Medical College of Wisconsin study (not prospective) • 2004 metronidazole first-line: 45% colectomy • 2005 vancomycin & decrease steroids: 25% colectomy
• Better outcomes with vancomycin in UC and non-severe CDI
• Vancomycin 125 mg po QID 10-14 days
• Fidaxomicin 200 mg po BID 10 days
• Fecal microbiota transplantation (FMT) for recurrent CDI • 3 episodes (2 recurrences or compassionate use)
Tremaine Wj. Clin Gastro Hep 2001;5. Issa M, et al. Clin Gastro Hep 2007;5.
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