Unit 2: UC and CD

What is the key anatomic difference between ulcerative colitis (UC) and Crohn's disease (CD)?

UC is limited to the colon and involves continuous inflammation beginning in the rectum. CD can affect any part of the GI tract and typically has patchy/transmural inflammation.

What is proctitis?

UC affecting only the rectum.

What is proctosigmoiditis?

UC affecting the rectum and sigmoid colon.

What is left-sided UC?

Inflammation begins in the rectum and extends to the splenic flexure.

What is right-sided UC?

Inflammation begins in the cecum and includes the ascending colon, hepatic flexure, and up to the right half of the transverse colon.

What is pancolitis?

UC affecting the entire colon.

What is Crohn's colitis?

Crohn's disease that affects only the colon.

What is gastroduodenal Crohn's disease?

CD affecting the stomach and the first part of the small intestine.

What is ileitis?

CD affecting only the ileum.

What is ileocolitis?

CD affecting the ileum and colon.

What is jejunoileitis?

CD affecting the upper half of the small intestine.

How do UC lesions differ from CD lesions?

UC produces continuously inflamed segments of the colon and is more superficial. CD can involve separated areas and may affect multiple GI locations with a cobblestone appearance.

What endoscopic findings are characteristic of active UC?

Continuous inflamed segments with vascular markings, granularity, friability, deep ulcerations, and spontaneous bleeding.

What subjective symptoms suggest active UC?

Abdominal cramping; frequent bowel movements with blood in the stool; eye pain/blurred vision; and raised, red, tender nodules.

What objective findings/labs can occur in UC?

Weight loss, nocturnal bowel movements/urgency, fever and tachycardia in severe disease, arthritis, hemorrhoids/anal fissures/perirectal abscesses, decreased Hgb/Hct, increased ESR/CRP/fecal calprotectin, leukocytosis and hypoalbuminemia in severe disease.

What symptoms are typical of Crohn's disease?

Chronic diarrhea, abdominal pain, and fatigue.

What objective findings/labs are important in Crohn's disease?

Fever, weight loss, stool testing for C. difficile and fecal calprotectin, anemia/CBC, CRP, and ESR.

What tests are generally used in evaluating IBD?

Stool testing, colonoscopy with tissue sampling, upper endoscopy, sigmoidoscopy, and capsule endoscopy when small-intestinal disease is inconclusive.

Why is a stool sample recommended in suspected IBD?

To rule out C. difficile infection.

What is colonoscopy used for in IBD?

It examines the colon and allows tissue samples to be obtained.

What is upper endoscopy particularly useful for?

It is a recommended test for Crohn's disease.

What is sigmoidoscopy?

Examination of the rectum and lower colon, including the sigmoid colon and anus.

When may capsule endoscopy be used?

To examine the small intestine when other evaluation is inconclusive.

What age range does the USPSTF recommend for colorectal cancer screening?

Adults ages 45–75 years.

How often is colonoscopy recommended in the slides for patients without UC?

Every 10 years.

How often is colonoscopy screening recommended for patients diagnosed with UC?

Every 1–3 years.

What are the UC treatment goals?

Achieve and maintain steroid-free remission, restore normal bowel frequency, decrease stools/day, control bleeding and urgency, achieve endoscopic mucosal healing, and reduce ulcers.

What is induction therapy?

Initial, generally more aggressive treatment intended to eliminate inflammation or decrease disease severity and induce remission.

What is maintenance therapy?

Treatment used to continue remission after induction, generally with less aggressive dosing.

Can some IBD drugs be used for both induction and maintenance?

Yes. The specific role depends on the drug and disease severity.

What is the first-line drug class emphasized for mild UC?

5-aminosalicylates (5-ASAs), such as mesalamine.

What is 5-ASA also called?

Mesalamine.

What is the mechanism of 5-ASA described in the slides?

It activates PPAR-gamma in colonic cells and blocks cyclooxygenase/inhibits prostaglandins in the colon.

What are examples of 5-ASA drugs?

Sulfasalazine, mesalamine, olsalazine, and balsalazide.

Which 5-ASA formulation targets the rectum directly?

Mesalamine suppository (Canasa).

Which 5-ASA formulation targets the rectum and distal colon?

Mesalamine enema (Rowasa).

How does sulfasalazine deliver mesalamine?

It is an azo-bonded prodrug released in the colon; sulfapyridine is absorbed systemically.

How does pH-dependent mesalamine release work?

The active drug is contained inside an enteric coating that releases it at a pH-dependent site.

How does time-dependent mesalamine release work?

Mesalamine microspheres release drug gradually independent of pH.

What are common adverse effects of sulfasalazine?

Abdominal pain, diarrhea, nausea, headache, and nasopharyngitis.

What serious adverse effects are associated with sulfasalazine?

Delayed hypersensitivity reactions such as SJS, myocarditis, interstitial nephritis; intolerance syndrome; nephrotoxicity; pancytopenia; and pericarditis.

What monitoring is emphasized for sulfasalazine?

Renal function (CrCl) before and during treatment; CBCs in patients ≥65 years old if also taking anticoagulants.

What is the treatment approach for mild-to-moderate UC involving only the rectum?

Rectal 5-ASA is used.

What is used for mild-to-moderate proctitis or left-sided UC?

Rectal 5-ASA enemas; topical corticosteroids may also be used.

What is used for left-sided UC when rectal 5-ASA alone is insufficient?

Combine rectal 5-ASA enemas with oral 5-ASA.

What is used for extensive mild-to-moderate UC?

Oral 5-ASA.

What should be done if a patient with mild-to-moderate UC fails an appropriately dosed 5-ASA?

Escalate to corticosteroids rather than simply trying a different 5-ASA formulation.

What budesonide formulation is emphasized for UC?

Budesonide MMX.

What is the role of budesonide MMX in UC?

It can induce remission in mild-to-moderate UC that is unresponsive to 5-ASA and is also used as first-line treatment in moderate-to-severe UC in the slides.

What is the typical budesonide MMX induction dose shown?

9 mg once daily in the morning for 8 weeks.

Why does budesonide have less systemic exposure?

It undergoes extensive first-pass metabolism in the liver.

What are common budesonide adverse effects listed?

Hypertension, peripheral edema, and headache/facial edema.

What serious effects can occur with prolonged/high-dose corticosteroids?

Cushing's syndrome and hyperglycemia; prolonged high-dose use should be avoided.

How can corticosteroid adverse effects be minimized after response?

Taper the dose after clinical response, using small decrements.

Should corticosteroids be used for maintenance of UC?

No; the slides recommend against corticosteroids for maintenance.

What is important about thiopurines for moderate-to-severe UC induction?

Monotherapy with thiopurines is not recommended for induction.

What is the role of thiopurines in UC maintenance?

They can be used for maintenance, including after corticosteroid induction.

Which anti-TNF is preferred in advanced-therapy-naive UC according to the slides?

Infliximab.

Which anti-TNF has higher efficacy than adalimumab for UC in the slides?

Golimumab.

What are examples of anti-TNF agents?

Infliximab, adalimumab, golimumab, and certolizumab pegol.

Which anti-TNF is used for moderate-to-severe Crohn's disease but not UC in the slides?

Certolizumab pegol.

What is a major black box warning shared by anti-TNF agents?

Serious infections, malignancy, and Hep B infection

What screening is required before starting an anti-TNF?

Test for tuberculosis (active and latent) and hepatitis B.

What vaccine counseling applies to anti-TNF therapy?

Avoid live vaccines.

What are common adverse effects of infliximab?

Infusion-related reactions, abdominal pain, and headaches.

What serious adverse effects are associated with infliximab?

Hypersensitivity reactions, heart failure, and hepatotoxicity.

What is primary non-response to a TNF agent?

Failure to achieve clinical response within 14 weeks of starting treatment.

What is loss of response to a TNF agent?

Initial response followed by progressive loss of response over time.

What factors can contribute to loss of response to TNF therapy?

Anti-drug antibodies and low serum trough drug concentrations.

What is ustekinumab's role in UC/CD?

It is an IL-12/23p40 antibody used for moderate-to-severe UC and Crohn's disease.

What is a key safety issue with ustekinumab?

Risk of infections; avoid live vaccines and monitor CBC, liver enzymes, lipids, and creatinine; test for TB before starting.

What is the mechanism of JAK inhibitors?

They block STAT phosphorylation, inhibiting downstream inflammatory responses.

What major black box warning is emphasized for tofacitinib?

Thrombosis, cardiovascular events, serious infections, and malignancy.

Is tofacitinib FDA-approved for Crohn's disease according to the slides?

No; the slides specifically note that Xeljanz is not FDA-approved for Crohn's disease.

What JAK inhibitor is listed for moderate-to-severe UC and Crohn's disease?

Upadacitinib.

What are IL-23p19 inhibitors listed in the slides?

Mirikizumab, risankizumab, and guselkumab.

What monitoring is emphasized before and during IL-23 inhibitor therapy?

Test for TB; monitor liver enzymes and bilirubin, with additional monitoring depending on the agent.

What is the mechanism of S1P receptor modulators?

They prevent lymphocytes from migrating into the colon and causing inflammation.

Which S1P modulators are listed?

Ozanimod and etrasimod.

What is ozanimod used for?

Moderate-to-severe ulcerative colitis.

What baseline monitoring is listed for ozanimod?

ECG, recent CBC, LFTs, ophthalmic assessment, and assessment for skin lesions.

What is the mechanism of vedolizumab?

It binds α4β7 integrin and blocks its interaction with MAdCAM-1, limiting GI-directed lymphocyte trafficking.

What is vedolizumab used for?

Moderate-to-severe UC or Crohn's disease.

What is vedolizumab's induction schedule in the slides?

300 mg IV at weeks 0, 2, and 6.

When should vedolizumab be discontinued for lack of improvement?

If there is no improvement by week 14.

What serious neurologic infection is associated with vedolizumab in the slides?

Progressive multifocal leukoencephalopathy (PML).

What are common side effects of vedolizumab?

Nausea, arthralgia, and headache.

What is azathioprine?

A thiopurine immunomodulator and prodrug; 6-mercaptopurine (6-MP) is the active drug in the body.

What is azathioprine used for in IBD?

Maintenance of remission in moderate-to-severe UC or Crohn's disease.

What is an important black box warning for azathioprine?

Increased risk of lymphoma/malignancy.

What testing should be performed before starting azathioprine?

TPMT testing to help guide dosing and assess toxicity risk.

What monitoring is emphasized with azathioprine?

CBC/platelets and liver function tests at frequent intervals, especially early in therapy.

Is methotrexate FDA-approved for UC or CD according to the slides?

No. It is not currently FDA-approved for UC or CD, but is used off-label for Crohn's disease.

What is the Crohn's disease role of methotrexate in the slides?

Moderate-to-severe CD induction with weekly parenteral methotrexate, followed by weekly maintenance.

What toxicities are important with methotrexate?

Hepatitis, neurotoxicity, myelosuppression, and pancytopenia.

What monitoring is needed with methotrexate?

TB/Hep B testing and monitoring of bone marrow, liver, lung, and kidney toxicity; renal function, pregnancy testing, hepatic function, ANC and platelets.

What is cyclosporine used for in UC?

Fulminant/severe UC, particularly as rescue therapy when IV corticosteroids fail.

What is the mechanism of cyclosporine?

It forms a complex with cyclophilin that inhibits calcineurin, reducing IL-2 production and T-cell activation.

What are important cyclosporine toxicities?

Hyperkalemia, hypomagnesemia, hepatotoxicity, nephrotoxicity, and PML.

What should be monitored with cyclosporine?

Trough levels, potassium, magnesium, BUN, and serum creatinine.