Inflammatory Bowel Disease

Question 1

specific goals for IBD treatment*

Answer 1

-3 treatment objectives:
-terminate the acute, symptomatic attack
-achieve complete remission of clinical and endoscopic disease activity -> why is this important? -> increased risk of colon cancer
-normal histology -> reoccurrence likely is less -> treat to target
-prevent recurrence of attacks

Question 2

5 ASA (5 aminosalicylic acid)

Answer 2

-Active tx of UC and Crohns
-ileum or colon
-Topically active agents with anti-inflammatory effects:
-Oral Mesalamine-COLON** (dont need to know the types)
-Delzicol 400mg 12/day
-Lialda 1.2g 4/day
-Apriso .375g 4/day

-Oral Mesalamine-terminal ILEUM and COLON -> Pentasa 500mg 8/day

-Oral Azo Compounds-released within COLON -> Sulfasalazine AND Balsalazide 750mg 9/day

-Topical mesalamine: deliver much higher 5-ASA to distal colon -> Canasa suppositories (RECTUM) AND Rowasa Enemas (REACHES WHOLE LEFT SIDE-> take laying down on left side)

Question 3

corticosteroids

Answer 3

-Used in short term tx of moderate to severe disease
-anti-inflammatory in combo with tx
-IV hydrocortisone or methylprednisolone -> continuous infusion or every 6 hours (sick in hospital)
-Oral prednisone or methylprednisolone, or budesonide
-Topical preparations: Hydrocortisone:
Suppositories (100 mg)
Foam (90 mg)
Enemas (100 mg)

Question 4

budesonide

Answer 4

-Oral glucocorticoid with high topical anti-inflammatory activity but low systemic activity
-more topical and less systemic absorption - steroid -> less SE
-Controlled-release formulation that targets delivery to terminal ileum and colon
-Less suppression of hypothalamic-pituitary-adrenal axis
-Fewer steroid-related effects

Question 5

mercaptopurine and azothioprine (just know they exist)

Answer 5

-Thioprine drugs
-Used to reduce or withdraw the corticosteroids and to maintain patients in remission
-Was used frequently with Biologics (helper)
-Allergic and nonallergic side effects (10%) -> Pancreatitis, bone marrow suppression, infections, hepatitis or cholestatic jaundice and higher risk of neoplasm
-Monitor CBC, LFTs

Question 6

methotrexate (she barely talked ab this in class)

Answer 6

-Used if intolerant to mercaptopurine (LAST RESORT)
-At low doses has anti-inflammatory properties -> inhibition of expression TNF-α in monocytes and macrophages
Given intramuscularly, subcutaneously, or orally
-SE: nausea, vomiting, diarrhea, alopecia, stomatitis, infections, bone marrow suppression, hepatitis, hepatic fibrosis, and life-threatening pneumonitis
-CBC, LFTs monitored
-Folate given

Question 7

biologics (dont need to know any names)

Answer 7

-organically made MONOCLONAL ANTIBODIES -> MAB (ending)
-no such things as a generic- not made in lab
-all of these interfere with inflammatory cascade (block immune)
-pretty much take it forever
-very effective
-give vaccines before therapy start!

-TNF Inhibitor:
Infliximab (IV)
Adalimumab (sq)
Certolizumab (sq)
Golimumab (sq)

-Integrin Blocker:
Vedolizumab (IV)- targets gut (less immunosuppression)
Natalizumab (IV)

-Interleukin Antagonist:
Ustekinumab (sq)
Risankizumab (sq)

-JAK Inhibitor: inhibits triggers in bowel
Upadacitinib (pill) - quick

Question 8

potential side effects of most biologics

Answer 8

-Sepis
-Pn
-Malignancy
-Lymphoma
-Myleosuppression
-Opportunistic infections
-Hepatic failure
-> Must monitor CBC and LFTS

Question 9

ulcerative colitis and crohns disease

Answer 9

-Ulcerative colitis:
-Chronic recurrent disease
-Diffuse MUCOSAL inflammation involving only the colon
-Invariably involves rectum and may extend proximally in a CONTINUOUS fashion to involve part or all of colon
-colon and rectum

-Crohn’s:
-Chronic recurrent disease
-from mouth to anus
-PATCHY TRANSMURAL inflammation involving any segment of the gastrointestinal tract from the mouth to the anus
-all layers of GI - (not just mucosal)

Question 10

epidemiology- 1.6 mil in US : ulcerative colitis and crohn’s

Answer 10

-US:
-15-30 and 50-80
-Slight > male
- > Jewish; white
-Runs in families
-Crohn’s:
-15-30 and 50-80
-Slight > female
- > Jewish; white
-Runs in families

-jewish > non-jewish white > african american > hispanic > asian
-runs in families

Question 11

IBD types/causes

Answer 11

-genetic
-environmental triggers
-immunologic

Question 12

genetics: IBD

Answer 12

• > 200 distinct susceptibility loci for IBD have been identified
  -very common in First-degree relatives -> same disease patterns
  -Clinical features of the disease demonstrate a heritable pattern -> Location
  -Several genetic syndromes associated with IBD

Question 13

immunologic: IBD

Answer 13

-Inflammatory mediators play an important role in the pathologic and clinical characteristics of these disorders
-autoimmune
-Immune response disrupts the intestinal mucosa and leads to a chronic inflammatory cascade

Question 14

ulcerative colitis

Answer 14

-Idiopathic inflammatory condition involving mucosal surface of colon
-Diffuse friability* and erosions with bleeding
-angery
-1/4 proctosigmoiditis
-1/2 left-sided colitis
-1/4 extensive colitis ->Extends more proximally +/- backwash ileitis (secondary involvement) -> pancolitis
-extraintestinal manifestations- HEENT, derm, MS

Question 15

ulcerative colitis S&S and PE

Answer 15

-based on severity of disease
-Frequency of BM*
-Rectal bleeding (UC>crohns) -> bc UC involves rectum and colon more
-Cramps
-Abdominal pain
-Fecal urgency
-Tenesmus
-Fever
-Wt change
-Extraintestinal manifestations
-physical exam- volume status, nutritional status, abdominal exam, rectal exam (perianal disease)

Question 16

extraintestinal manifestations

Answer 16

-25% of patients with IBD:
-Oligoarticular or polyarticular nondeforming peripheral arthritis
-Spondylitis or sacroiliitis
-Episcleritis or uveitis
-Erythema nodosum- hot, red, tender (1-5cm) and found on anterior surface of lower legs, ankles, calves, thighs, and arms
-Pyoderma gangrenosum- common of dorsal surface of feet and legs (can also occur on arms, chest, stoma, and even face) -> begins as pustule and spreads concentrically -> then ulcerates with violaceous edges surrounded by margin of erythema, centrally they contain necrotic tissue with blood and exudates
-Sclerosing cholangitis- UC typically
-Thromboembolic events

Question 17

serologic testing ulcerative colitis

Answer 17

-Antineutrophil cytoplasmic antibodies with perinuclear staining (p-ANCA):
-5–10% of pts with Crohn’s disease
-50–70% of patients with ulcerative colitis**

-Antibodies to the yeast Saccharomyces cerevisiae (ASCA):
-60–70% of patients with Crohn’s disease**
-10–15% of patients with ulcerative colitis

-sensitive not specific -> false pos/neg is common so cant be used to rule in or out
-not very helpful, not really done

Question 18

labs for IBD

Answer 18

-do this with chronic -> rule out
-CBC- anemia?
-CMP
-ESR
-CRP
-Fecal Calprotectin, infection -> high with IBD *
-rule out c diff

-New onset: R/o other conditions: stool studies, thyroid tests, celiac panel

Question 19

assessment of disease activity- ulcerative colitis (just an idea)

Answer 19

-stool freq - < 4 (mild), 4-6 (moderate), > 6 mostly bloody (severe)
-pulse/min - < 90 (mild), 90-100 (moderate), > 100 (severe)
-HCT% - normal (mild), 30-40 (moderate), < 30 (severe)
-Wt loss % - none (mild), 1-10% (moderate), >10% (severe)
-temp f - normal (mild), 99-100 (moderate), >100 (severe)
-ESR - <20 (mild), 20-30 (moderate), >30 (severe)
-albumin - normal (mild), 3-3.5 (moderate), <3 (severe)

Question 20

diagnosis: colonoscopy- ulcerative colitis

Answer 20

-you need a colonoscopy for dx -> multiple blind bx
-In acute colitis -> dx is established by sigmoidoscopy or colonoscopy with bx
-Edema, friability (bleeds easily), mucous, and erosions
-Crypt abscess and destruction seen on pathology
-MC finding- extensive ulceration of mucosa
-irregular, diffuse erythematous, submucosal hemorrhage
-CONTINUOUS
-mucopurulent exudate
-pseudopolyps may form as reaction to inflammation
-cant see vessels
-narrow lumen

Question 21

crohn’s observation

Answer 21

-ulceration are deep and have skip lesions

Question 22

differential- ulcerative colitis

Answer 22

-Infectious colitis
-STDs causing proctitis
-Ischemic colitis
-Radiation proctitis- prostate cancer- corkscrew vessels
-Crohn’s DS
-IBS
-Diverticulitis

Question 23

risk of colon cancer- ulcerative colitis

Answer 23

-Risk factors for cancer in UC :
-Long-duration disease
-Extensive disease
-Family history of colon cancer
-Colon stricture
-Postinflammatory pseudopolyps on colonoscopy
- >8-10yrs of pancolitis or 12-15yrs of L sided colitis: Colonoscopy every 1-2yrs with multiple biopsies *

Question 24

surgery in UC

Answer 24

-Incidence has decreased- more meds
-Severe hemorrhage, perf, cancer, toxic megacolon
-Total proctocolectomy with ileostomy = cure
-Ileoanal pouch anastamosis:
-40% pouchitis- inflammation of internal pouch made -> antibiotics or…
-May require conversion to standard ileostomy

Question 25

specific tx of UC: diet

Answer 25

-Depends on extent of colon involved and severity of illness -Diet: -Regular diet but limit intake of caffeine and roughage (esp roughage if stricture) -strictures- should be on low fiber diet -is there Lactose intolerant -is there an Overlap with IBS- COMMON -Enteral supplements if malnourished

Question 26

distal colitis tx : proctitis and proctosigmoiditis

Answer 26

-proctitis (rectum): -Mesalamine suppositories -Hydrocortisone foam -Hydrocortisone suppositories -things local to rectum -Proctosigmoiditis (rectum and sigmoid): -Mesalamine enema -Hydrocortisone enema -enema- left side -> not long term

Question 27

tx of UC: mild to moderate

Answer 27

-Mesalamine tablets- Lialda, Delzicol, Apriso -Azo Compounds- Sulfasalazine and Balsalazide -Enemas- flares -Oral Prednisone or Budesonide- flares -Biologics, Azathiopurine or mercaptopurine- moderate

Question 28

tx of UC: severe

Answer 28

-Prednisone 40–60 mg IV daily -switch to oral -TAPER- months long taper or else flare -NPO, IVF, transfuse if needed -Consider: Abd xray to look for toxic megacolon -Send stools work up -Surgical consult -Biologic +/- mercaptopurine

Question 29

toxic megacolon

Answer 29

-<2% of cases of UC -catastrophe- rare -Colonic dilatation of > 6cm on plain films + signs of toxicity -In addition to the therapies outlined above-NG tube -Roll from side to side and onto abdomen in effort to decompress distended colon

Question 30

remission in UC

Answer 30

-75% in remission will relapse within 1 year -Long-term maintenance therapy required or else relapse: -*Mesalamine tablets - Lialda, Delzicol, Apriso -*Azo Compounds- Sulfasalazine and Balsalazide -Frequent disease relapses (more than two per year) or steroid-dependent: -Biologic - +/- Mercaptopurine or azathioprine

Question 31

crohn's disease

Answer 31

-anywhere from mouth to anus -1/3 small bowel only, MC terminal ileum (ileitis) -40-50% small bowel and colon, most often terminal ileum and adjacent proximal ascending colon (ileocolitis) -20% colon alone - tricky (how do we differentiate UC) -1/3 have associated perianal disease (fistulas, fissures, abscesses) -Small number involvement of the mouth (aphthous ulcers) or upper intestinal tract -transmural process (through more layers of GI tract)- mucosal inflammation and ulceration, stricturing, fistula and abscess formation

Question 32

signs and symptoms of crohn's

Answer 32

-varies: -Location of involvement -Severity of inflammation -Extra-intestinal manifestations -> ileal disease -> bile salt, B12 issue, kidney stones -REFER TO SLIDES 16-23- everything else is same as UC pretty much -MC presentaitons: -Chronic inflammatory disease -Fistualization with or without infection -Perianal disease -Extraintestinal manifestations

Question 33

crohn's disease differential disease

Answer 33

-IBS -Appendicitis -Intestinal Lymphoma -Infectious or Ischemic Colitis -Diverticulitis -STD -UC -Radiation proctitis

Question 34

crohns: chronic inflammatory disease presentation

Answer 34

-Most common presentation -Often seen in patients with *ileitis or ileocolitis* -Low-grade fever and malaise -Weight loss -Loss of energy -Diarrhea (typically nonbloody and often intermittent) -> UC is more bloody -Cramping or steady RLQ or periumbilical pain

Question 35

crohns: intestinal obstruction

Answer 35

-STRING SIGN- stricturing -proximal dilation -Due to long-term chronic inflammation -Most often later in disease from chronic fibrosis without other systemic symptoms or signs of inflammation -Postprandial bloating, cramping pains, and loud borborygmi

Question 36

crohns: fistualization +/- infection

Answer 36

-communication that should not be happening caused by infection -transmural disease -translocation of bacteria -colon, bladder, vagina, small bowel -Sinus tracts that penetrate through the bowel and form fistulas to a number of locations: -Mesentery -Small intestine or stomach -Bladder or vagina -Enterocutaneous -Presentation varies based on location -perirectal fistual- enterocutaneous -> drains to outside

Question 37

crohns: perianal disease

Answer 37

-1/3 of patients with either large or small bowel involvement develop perianal disease: -Anal fissures -Perianal abscesses -Fistulas

Question 38

lab findings with crohns disease

Answer 38

-Poor correlation between laboratory studies and clinical picture -Reflect inflammatory activity or nutritional complications of disease -CBC, CMP, ESR, CRP, Fecal calprotectin (high) -Rule out other ds: celiac panel, thyroid disease, stool studies

Question 39

serologic studies in IBD?

Answer 39

-Antineutrophil cytoplasmic antibodies with perinuclear staining (p-ANCA): -5–10% of patients with Crohn’s disease -50–70% of patients with ulcerative colitis**** -Antibodies to the yeast Saccharomyces cerevisiae (ASCA) : -60–70% of patients with Crohn’s disease***** -10–15% of patients with ulcerative colitis -sensitive but not specific

Question 40

dx studies for crohns

Answer 40

-Initial diagnosis of Crohn’s disease is based on a compatible clinical picture with supporting endoscopic and radiographic findings: -Colonoscopy/Flex Sig - visualize and bx but cant see everything so we must also do... -MR Enterography** -Capsule Endoscopy -not really bc we are concerned of stricture

Question 41

crohn's disease- colonoscopy

Answer 41

-Evaluate colon and terminal ileum and bx -Typical endoscopic findings: -Aphthoid (earliest), linear or stellate ulcers (also longitudinal) -Strictures, segmental involvement (skip lesions) -Cobblestoning in advanced ds- nodular thickening -Granulomas seen in 25%; highly suggestive of Crohn’s disease** -big deep ulcerations * -nodules that narrow

Question 42

complications of crohns ds

Answer 42

-Malabsorption -Abscess -Obstruction -Fistulas -Perianal Ds -Carcinoma -Hemorrhage (rare)

Question 43

carcinoma- crohns

Answer 43

-8 or more years of Crohn’s colitis -Colonoscopy to detect dysplasia** or cancer every 1-2 years -NOT POLYPS -Increased risk of small bowel cancer and lymphoma -> rare

Question 44

treatment of crohns disease

Answer 44

-Diet: -Well-balanced diet with as few restrictions as possible -D/c caffeine -R/o lactose intolerance -Patients with stricture/active inflammation -> Low-roughage/fiber diet -enteral therapy- for Children and adolescents with poor intake and growth retardation -TPN : -short term in pts with active disease and progressive weight loss -Awaiting surgery & can’t tolerate enteral feedings -> Obstruction, high-output fistulas, severe diarrhea, or abdominal pain (severe) -resection > 100cm of terminal ileum or if extensive ileal disease: -fat malabsorption- low fat diet -b12 malabsorption- supplementation

Question 45

crohn's disease- symptomatic relief of diarrhea

Answer 45

-Bile salt malabsorption- Responds to cholestyramine 2–4 g -Bacterial overgrowth: rifaximin (fistulas) -Lactose intolerant

Question 46

specific drug therapy for crohn's

Answer 46

-Mild to moderately active ileocolonic or colonic disease -5 ASA agents: Mesalamine: -Pentasa 500mg 4 tabs 2x day (ileocolonic)* -Delzicol 400mg 12/day -Lialda 1.2g 4/day -Apriso .375g 4/day -Steroids: Budesonide - 9mg/day then for 8-16 weeks then tapered -severe disease- Prednisone: 40-60mg/day…60-90% have remission in 2weeks -> Very slow taper -> then Biologic +/- Immune modulators

Question 47

crohns- hospitalize

Answer 47

-Persisting symptoms despite oral corticosteroids -High fever -Persistent vomiting -Evidence of intestinal obstruction -Severe weight loss -Severe abdominal tenderness

Question 48

surgery crohn's

Answer 48

-In the past a substantial number of pts required at least one surgical procedure -Indications for surgery: -Intractability to medical therapy -Intra-abdominal abscess -Massive bleeding -Symptomatic refractory fistulas -Intestinal obstruction

Question 49

microscopic colitis (this is its own thing)

Answer 49

-Idiopathic -Up to 15% of pts who have chronic or intermittent non-bloody watery diarrhea with normal-appearing mucosa at endoscopy -2 major subtypes—collagenous colitis and lymphocytic colitis -infiltration with collagen or lymphocytes - > women, esp fifth to sixth decades -Chronic or recurrent; my remit after several years -voluminous watery diarrhea

Question 50

microscopic colitis: eval and dx and management

Answer 50

-Routine labs, stool studies, celiac panel -Colonoscopy, with multiple mucosal bx: -Collagenous colitis -characterized by colonic subepithelial collagen band >10 micrometers in thickness. -Lymphocytic colitis (association with celiac)- characterized by intraepithelial lymphocytic infiltrate (≥20 lymphocytes per 100 epithelial cells) -management: -General measures for all pts: -advised to avoid nonsteroidal anti-inflammatory drugs and, if possible, d/c medications associated with microscopic colitis -Budesonide for pts with active disease****- for active disease