Resident Editor: AdamTabbaa, MD

Faculty Editor: Fernando Velayos, MD

Background

• Ulcerative colitis (UC) = diffuse submucosal (superficial) inflammation limited to the colon, extending proximally from rectum.  Subsets defined by extent of inflammation (proctitis, proctosigmoiditis, left-sided, and pancolitis).
• Crohn’s disease (CD) = transmural (all layers bowel wall) inflammation of the GI tract.  Occurring anywhere from the mouth to the anus, often in a pattern of skip lesions (vs. continuous involvement of UC). The transmural inflammation gives rise to the complications of CD, and CD can be divided into subtypes based on these as well (stricturing, fistulizing, obstructing).

Epidemiology

• Most common ages 15-40, second peak ages 50-80. 
• M:F = 1:1
• Affects all races and ethnicities, but 2-8-fold increase in Ashkenazi Jews
• Smoking protective for UC, worsens Crohn’s

Signs and symptoms

• Overlap: weight loss, fever, abdominal pain, blood diarrhea (more common in UC), anemia
• Ulcerative colitis: rectal urgency
• Crohn’s disease: Depends on area affected-odynophagia, dysphagia, fistulas, abdominal abscesses, perianal disease including skin tags or anal fissures, aphthous ulcers, fat malabsorption, gallstones, B12 deficiency/pernicious anemia.
• Extra-intestinal manifestations can be seen in either UC or Crohn’s Disease (see below)

Diagnosis

• Typically made by a suggestive history, abdominal imaging and colonoscopy with biopsy. Always rule out infection if suspecting active IBD, as ultimately if diagnosed with IBD the patient will be given immunosuppressing medications!
• C. diff PCR, stool bacterial culture (Shigella, Salmonella, Campylobacter, E. coli 0157, Yernia), stool ova & parasite (Amoebiasis), in immunocompromised hosts consider CMV, Kaposi’s sarcoma, and HSV
• Also consider ischemic colitis and malignancy when approaching undifferentiated inflammatory diarrhea
• CBC, iron studies, CRP, fecal calprotectin
• GI referral and colonoscopy or EGD if indicated

Treatment

• Tiers of therapy are based on severity of symptoms, some patients have mild disease requiring mild therapies, others are refractory to steroids and immune therapies
• New therapies are being introduced for use in IBD after having displayed some efficacy in rheumatologic conditions (vedolizumab, tofacitnib)
• Currently no role for combined biologic therapy in IBD, however this is an area of current exploration, with a trial underway exploring the use of vedolizumab in conjunction with adalimumab in Crohn’s Disease

• Before initiating therapy:
  • PPD/Quantiferon Gold
  • hepatitis serologies (remember risk of HBV reactivation)
  • Ensure routine live vaccinations have been given (contraindicated once therapy has begun)
  • TPMT level (to assess phenotype regarding bone marrow suppression by AZA/6-MP) should be routinely checked
• Also consider contraindications to immunomodulator therapy: active infection, untreated latent TB (would not be contraindication to vedolizumab), preexisting demyelinating disease, CHF, active/recent malignancy
• General principles are similar to oncology: induction therapy and then maintenance to maintain the disease in remission

Treatment of Ulcerative Colitis

1. Make Diagnosis and Assessment
2. Assess Comorbidities and Disease and Therapy-Related Complications
   1. Treat infection (C. diff, CMV, other bacteria, parasites)
   2. Stop aspirin or NSAIDs
   3. Monitor for DVT/PE
   4. Colectomy if colorectal cancer or certain histological criteria for dysplasia
   5. Consult surgery if toxic megacolon or fulminant colitis
3. Stratify According to Colectomy Risk
   1. Low Risk → limited anatomic extent, mild endoscopic disease
   2. High Risk → extensive colitis, deep ulcers, age <40, high CRP, steroid-requiring disease, history of hospitalization, C. diff infection, CMV infection
4. Inductive and Maintenance Therapy for Low-Risk Patients (Outpatient)
   1. Oral 5-ASA and/or
   2. Rectal 5-ASA and/or
   3. Oral budesonide or prednisone and/or
   4. Rectal steroids
   5. If remission, taper steroids over 60 days and maintain therapy with 5-ASA PO/PR
   6. If no remission, see #5
5. Inductive and Maintenance Therapy for High-Risk Patients (Outpatient)
   1. Short course of steroids with initiation of thiopurine OR
   2. Anti-TNF w/wo thipurine OR
   3. Vedolizumab, w/wo thiopurine
   4. If no remission, see #6
   2. Therapy for High-Risk Outpatient not in Remission
      1. Complicated, managed by IBD specialist
      2. Options similar to above, but consider reasons for failed therapy (insert) and possible need for proctocolectomy
   3. Therapy for High-Risk Inpatient
      1. IV steroids, infliximab, cyclosporine, colectomy

​Treatment of Crohn’s Disease

1. Make Diagnosis and Assess Inflammatory Status
   1. History, exam, labs, imaging, endoscopy
2. Assess Comorbidities and Disease-Related Complications
   1. Infection (C. diff, CMV, other bacteria, parasites)
   2. Stricture/remodeling (obstruction, weight loss)
   3. Symptoms related to prior surgery (bile acid diarrhea, bacterial overgrowth, steatorrhea/malabsorption)
   4. Abdominal or perianal abscess or fistula
3. Identify and Low-Risk or High-Risk
   1. Low-Risk
      1. Age >30 at initial dx, limited anatomical involvement, no perianal and/or severe rectal disease, superficial ulcers, no prior resection, no stricturing
   2. Moderate/High-Risk
      1. Age>30, extensive anatomical involvement, perianal and/or severe rectal disease, deep ulcers, resections, stricutring
4. Initial Treatment for Low-Risk Patients
   1. Steroids with or without AZA
5. Initial Treatment for Moderate/High-Risk Patients
   1. Use anti-TNF monotherapy over no therapy or thiopurine monotherapy
   2. Use anti-TNF + thiopurine over thiopurine monotherapy or anti-TNF monotherapy
   3. Use MTX in pts who don’t tolerate purine analog in combination with anti-TNF

​When to refer

• All patients with suspected IBD should be referred to GI for endoscopic confirmation of the diagnosis as well as treatment. It is reasonable to conduct basic labs and studies as above to rule out other causes before referral.

Follow-up/Surveillance malignancy screening

• When IBD patients come to the ED with severe abdominal pain, CT Abdomen & C. diff toxin should be first tests of choice if too unstable for colonoscopy with biopsies.  Consider surgical consultation early.
  • For patients with repeated CT scans, MRI Pelvis may be useful, particularly for peri-anal disease
• Annual or biannual surveillance colonoscopies with biopsies are indicated for cancer surveillance after 8-10 years of UC due to the markedly increased risk of colorectal cancer
• There are no formal guidelines by the ACG for malignancy screening for CD due to the insufficient evidence, however, the American Gastrointestinal Association recommends following the same surveillance criteria as for UC

​References

Kornbluth A, Sachar DB. Ulcerative colitis practice guidelines in adults (update): American College Gastroenterology, Practice Parameters Committee. Am J Gastroenterol 2010;105:501-523. 

Lichtenstein GR, Hanauer SB, Sandborn WJ. Management of Crohn's disease in adults. Am J Gastroenterol 2009;104(2):465-83.

Hirten, Robert P. et al. Combining Biologics in Inflammatory Bowel Disease and Other Immune Mediated Inflammatory Disorders Clinical Gastroenterology and Hepatology, 2018

Lichtenstein, G. et al. ACG Clinical Guideline: Management of Chron’s Disease in Adults, 2018

American Gastroenterological Association Ulcerative Colitis Clinical Care Pathway 2018