Management of the Hospitalized IBD Patient

Drew DuPont MD

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)

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

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.

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

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

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

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

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.

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?

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.

Sutherland L, et al. Gut. 1991;32(9):1071.

Active Crohn’s Disease

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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

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

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.

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.

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.

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

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

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.

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

Clostridium difficile in IBD

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

Issa M, et al. Clin Gastro Hep 2007;5

Pseudomembranes in 50-60% of non-IBD vs. 0-10% in IBD

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.