What other diseases are included under the umbrella of "inflammatory bowel disease"?

IBD in it's acute presentation can look just like infectious colitis, how can you tell them apart?

How deep does ulcerative colitis go?

- depends on what you mean. It's more distal than proximal, and they've seen rectal sparing

- disease is confined to the mucosa and perhaps the superficial submucosa.

- in severely active disease inflammation can be transmural.

Ulcerative proctitis.

- this is pretty much ulcerative colitis of the rectum

- you have to take a biopsy from above 15 cm to prove that there is not at least histological inflammation outside of the rectum.

- this is not associated with an increased risk of rectal neoplasia (whereas UC, ulcerative colitis, is!)

Chron's disease

- chronic inflammatory disease affecting anywhere from mouth to anus.

- transmural and focal, with skip areas in the bowel

- terminal illeum is most common site (bout 75% have ileal disease).

- manifests with: inflammation with ulcers, swollen bowel, friable blow with bleeding, strictures, fistulas. (Many pts progress to fisures or strictures.

Indeterminate colitis.

- any colitis regardless of severety where neither UC or Chron's disease could be diagnosed with certainty.

- this is at most 10% of ppl with IBD

- sometimes over time the person will become diagnostic of either UC or Chron's

- If they see fistulas, granulomas, or small bowel disease, they give the dx of Chron's.

Give us some epidemiology information about IBD

- Canada has the highest Crohn's and UC in the world.

- 0.5% of ppl

- peak age is 3rd degade

- more in females for Chron's

- UC doesn't affect mortality, Chron's has slightly higher than normal mortality

What is the pathogenesis of IBD thought to be?

- happens in pts with an underlying genetic predisposition, where their intestinal immune system responds with an exuberant response to a yet to be defined antigen (don't know if that's a floral Ag, or exogenous microbe or food particle)

- genetic pattern

- NOD-2/CARD 15 gene was identified as the first genetic mutation associated with a complex chronic immune disease. NOD-2 especially, so if you have that gene mutation then you're more likely to have the diease, and it has a role in bacterial recognition.

- SMOKING is linked to Chron's and UC.

How do we diagnose Chron's and UC? (Part 1)

- colonoscopy

- with biopsy

- at colonoscopy often the ileum can be accessed

- upper endoscopy only if symptoms warrant.

- barrium swallow and small bowel follow through is used, but now we do more cross sectional imaging. Also Barium enema is sortof less effective than a colonoscopy.

- plain abdominal X-rays (bowel obstruction, acute colitis where you're concerned about perforation or megacolon).

How do we diagnose Chron's and UC? (Part 2)

- cross sectional imaging includes abdominal ultrasound which can identiry thickened loops of bowel, dilated loops of bowel and increased vascular flow (by Doppler) which can be a sign of chron's.

- CT scans are widely used (regular pathology as well as fistulas, pelvic disease and extraintestinal diseases.

- abdominal MRI

- barium oral contrast can be used with MRI or CT

- video capsule endoscopy is last resport after all that.

- even better is double balloon endoscopy either from top or bottom.

- blood tests showing p-ANCA have been associated with UC or Chron's. (it would guide you away from thinking non-inflammatory), high WBC can reflect active inflammation, low Hb active bleeding, low albumin malnutrition or active inflammation (with catabolism of body proteins)

- CRP used more often than ESR

Describe some extraintestinal diseases associated with IBD

- Arthritis (most common) - arthralgias during active luminal disease, ankylosing spondylitis, pauciarticular or polyarticular frank peripheral arthritis

- Psoriasis

- Pyoderma gangrenosum

- Erythema nodosum

- Primary sclerosing cholangitis and cholangiocarcinoma (increased risk for colorectal dysplasia and may lead to liver failure).

- NAFLD

- osteoporosis and bone fractures (could be due to steroid therapy)

- deep vein thrombosis

- cancer, most commonly colorectal cancer.

Describe the 5-ASA treatment for colitis

- 5-aminosalicylates. from the parent sulfasalazine. (they use different forms to get it to the colon w/o being digested)

- has a local effect of colonic mucosa likely by reducing inflammatory mediators from granulocytes and possibly by inducing inflammatory cell apoptosis.

Do ppl use abios to treat IBD?

- sure do.

- metronidazole and ciprofloxacin can treat perineal fistulas and complicated abscesses.

- they can improve luminal disease

- they may remove some of the more potentially injurious organisms

Do an overview of corticosteroid side effects

Right away: mood changes

Annoying: unwanted weight gain, hirsuitisn, acne, irritability, mood swings, depression

More serious: osteoporosis (reversible), premature catacts, immunocompromization and infection susceptibility.Delay wound healing after sx.

- usually given as prednisone orally or hydrocortisone or methylprednisolone IC. Liquid or foam enema

- anti-inflammatory effects and immunomodulation (reduces adaptive immune responses).

Describe purine analogs and methotrexate in the treatment of IBD

- Purine analogs induce T cell apoptosis and reduce the presence of the activated cells that orchestrate the aberrant immune response.They may induce cytopenia, mainly leucopenia but also thrombocytopenia. (so monitor their blood regularly). We use these when they become steroid resistent or dependent. SE include GI intolerance and frank allergy.

- Methotrexate. Another option other than purine analog. SE is feeling flu-like 24-48 hours after dosing, liver fibrosis. Blood counts and LEs monitored monthly. Induces T cell apoptosis. Some docs do liver biopsies to assess for liver damage.

Antibody-related txs for IBD (so immunomodulators)

- Monoclonal Ab to TNF-a.Both the two following are anti-TNF-a drugs.

- Infliximab, great for some. SE includes increase in infections, increase in neoplasms.

- Adalimumab (Humira) is approved for Chron's. It is a human form of anti-TNF-a that is likely less immunogenic compared to inflicimab. Toxicity and efficacy is similar to infliximab.

Calcinurin inhibitors

- ex; cyclosporin A and Tacrolimus

- used for graft rejection and graft vs. host disease and also UC (acute severe)

- calcineurin is a player involved in IL-2 and Th2 activation, so it's an immune thing.

When might you do intestinal transplantation for someone with IBD? What's Pouchitis?

- you'd do it if they've developed short bowel syndrome (from repeated resections for Chron's) and for those who are failing total parenteral nutrition (cause of loss of vascular access or recurrent sepsis or liver failure).

- Pouchitis is a complication surgery for UC that involves a total colectomy. They could be left with the terminal ileum brought out as a stoma or have their ilium make into an ileoanal pouch and anastamosed to the anus. Pouchitis can be treated with abios.

Describe the risk of getting cancer if you have IBD.

-by 30 years of disease, at most 15% of people have developed colorectal cancer.

- most recommend colectomy if dysplasia is present

- increased risk when there's also 1ary sclerosing cholangitis, long duration of disease, more extensive colitis, multiple pseudopolyps and fam hx of colorectal ca.