Gi 14: Inflammatory Bowel Disease

Front 1

How many cases of IBD are there in the US? UC vs CD?

Back 1

> 1 million
50% UC and 50% CD

Front 2

How many new cases of IBD are there per year? How many total cases of IBD are there / 100,000?

Back 2

- New cases: 10 / 100,000 / year
- Total cases: >200 / 100,000 in the West

Front 3

What is the long-term outlook of IBD?

Back 3

- Chronic, lifelong disease without medical cure
- Surgery often necessary

Front 4

Where are the highest incidences of IBD in the world?

Back 4

- US
- Canada
- Europe

Front 5

What part of the GI tract is affected by Ulcerative Colitis? Pattern?

Back 5

- Continuous inflammation
- Colon only, superficially affects mucosa, lamina propria, and submucosa
- Starts at rectum and works its way proximally

Front 6

What is the clinical presentation of Ulcerative Colitis?

Back 6

- Diarrhea (bloody w/ mucus)
- Abdominal pain and tenderness
- Loss of appetite and weight
- Fever
- Fatigue
- Urgency for BM
- Children: growth and developmental failure

Front 7

What findings are there of Ulcerative Colitis on endoscopy?

Back 7

- Erythema
- Loss of usual fine vascular pattern
- Granularity of mucosa
- Friability
- Edema
- Pseudopolyps
- Erosions and ulcers
- Spontaneous bleeding
- Cecal patch
- Backwash ileitis

Front 8

What does this endoscopy show?

Back 8

- Mild ulcerative colitis with loss of vascular pattern
- Hard to see the blood vessels
- Some whitening = accumulation of immune cells

Front 9

What does this endoscopy show?

Back 9

Severe ulcerative colitis
- Spontaneous bleeding and friability
- Occult blood leaking in from bowel
- White blobs are mucus, neutrophils, macrophages, and lymphocytes leaking into lumen

Front 10

What does this endoscopy show?

Back 10

Ulcerative Colitis
- Erythematous
- Friable
- Loss of vascular pattern
- Also notice continuous and circumferential pattern

Front 11

What does this endoscopy show?

Back 11

Ulcerative Colitis
- Inflammatory pseudopolyp - outpouching of inflammatory cells predominantly seen in UC
- Large population of goblet cells covers the pseudopolyps with mucous

Front 12

What does this endoscopy show?

Back 12

Ulcerative Colitis
- Lots of Pseudopolyps decreasing the size of the lumen

Front 13

What is the remission rate of Ulcerative Colitis?

Back 13

Around 40% no matter how many years after diagnosis

Front 14

What are the potential outcomes of Ulcerative Colitis over time?

Back 14

- Colectomy (up to 20%)
- Disease activity persists (30-50%)
- Remission (~40%)

Front 15

What are the possible disease severities in Ulcerative Colitis? How common?

Back 15

- Low activity (20%)
- Moderate to Higher activity (71%)
- Fulminant disease (9%)

Activity = patients presenting with symptoms of their disease (diarrhea, pain, etc)

Front 16

What is meant by Fulminant Colitis?

Back 16

Severe UC, with:
- Fever, elevated WBC count, and unstable vitals
- High risk of perforation

Front 17

How do you diagnose Fulminant Colitis?

Back 17

- Usually full colonoscopy not necessary
- Flex sig only to rule out other causes such as C. difficile and take biopsies

- Otherwise based on presence of fever, elevated WBC count, and unstable vitals

Front 18

What part of the GI tract is affected by Crohn's Disease? Pattern?

Back 18

- Patchy inflammation
- Mouth to anus involvement
- Full-thickness inflammation (all layers of the bowel wall)

Front 19

What are the characteristics that indicate Crohn's Disease?

Back 19

- Variable involvement
- "Cobblestone" appearance
- Fistulae
- Strictures

Front 20

What is the most common location to be affected by Crohn's Disease?

Back 20

Ileocecal area

Front 21

How common is Crohn's Disease that only affects the small intestine? Only the large intestine? Both small and large intestine?

Back 21

- Small intestine: 30%
- Large intestine: 20-25%
- Small AND Large intestine: ~50%


(remember UC always only affects the large intestine)

Front 22

What is the typical clinical presentation of Crohn's Disease?

Back 22

Usually in pediatric population (<18 years):
- Abdominal pain
- Diarrhea and occasionally rectal bleeding (bleeding less common in CD)
- Weight loss
- Anorexia (failure to thrive)
- Vomiting
- Stunted growth
- Fevers

Front 23

How does Crohn's Disease that presents in an adult differ from that which presents in a pediatric patient?

Back 23

- Similar symptoms
- Growth and development issues less apparent
- Often had silent disease as a child / teen

Front 24

What are the three major endoscopic findings that are specific for Crohn's Disease?

Back 24

- Aphthous ulcers (looks like a canker sore)
- Cobble-stone appearance
- Discontinuous lesions

Front 25

What does this endoscopy show?

Back 25

Crohn's Disease with linear ulcerations

Front 26

What does this endoscopy show?

Back 26

Crohn's Disease: skip lesions (areas of inflammation are adjacent to normal mucosa)

Front 27

What does this endoscopy show?

Back 27

Crohn's Disease: Cobble-stone appearance

Front 28

What findings favor a diagnosis of Crohn's Disease?

Back 28

- Rectal sparing (UC always affects the rectum)
- Normal vasculature next to affected tissue (skip lesions)
- Isolated involvement of the terminal ileum (pancolitis/UC can have backwash ileitis where the lesion extends up to the ileum)
- Fistulas or Strictures
- Granulomas on biopsy

Front 29

What are the extra-intestinal manifestations of IBD?

Back 29

- Acute Arthropathy (knees, spine, proximal joints of hands): 15-20%
- Erythema Nodosum (red rash on shins): 15%
- Choledocholithiasis: 15-30%
- Ocular complications: 5-15%
- Sacroiliitis: 9-11%
- Nephrolithiasis: 5-10%
- Ankylosing Spondylitis: 3-5%
- Pyoderma Gangrenosum: 1-2%
- Primary Sclerosing Cholangitis: 1-2%
- Amyloidosis: rare

Front 30

Which extra-intestinal manifestations are more common in Crohn's Disease?

Back 30

- Ankylosing Spondylitis (3-5%)
- Nephrolithiasis (later on in CD in patients who have had surgery): 5-10%

Front 31

Which extra-intestinal manifestations are more common in Ulcerative Colitis?

Back 31

- Pyoderma Gangrenosum: 1-2%
- Primary Sclerosing Cholangitis: 1-2%

Front 32

What is this? What is it associated with?

Back 32

Erythema Nodosum: painful and tender extra-intestinal manifestation of IBD (15%)

Front 33

What is this? What is it associated with?

Back 33

Pyoderma Gangrenosum: violet tinge at endges of rash, extra-intestinal manifestation of IBD (more common in UC) (1-2%)

Front 34

What is this? What is it associated with?

Back 34

Ocular complications (5-15%), extra-intestinal manifestation of IBD:
- Left: Episcleritis - white part of eye is very inflamed, usually not painful, more of a cosmetic issue
- Right: Uveitis - painful inflammation of the iris that hurts between light and dark rooms as the iris contracts

Front 35

What are the goals of management of IBD?

Back 35

- Confirm accurate diagnosis
- Induce remission (absence of inflammatory symptoms and feeling "well")
- Maintain remission
- Avoid surgery when possible
- Enhance quality of life
- Avoid complications of disease and therapy

Front 36

How common is maintenance therapy in patients in remission from IBD?

Back 36

- 95% of patients require maintenance therapies
- Transition to maintenance occurs AFTER a successful induction

Front 37

What genetic abnormalities are associated with CD and UC? How common?

Back 37

Crohn's Disease:
- NOD2 mutations: 35-40% of patients with this mutation get the disease (incomplete penetrance) and not all patients w/ CD have this mutation
- Only associated with CD (not UC)
- Concordance rate for monozygotic twins is approximately 50%

Ulcerative Colitis:
- Concordance rate for monozygotic twins is only 16%, suggesting that genetic factors are less dominant

Front 38

What is the function of the NOD2 gene?

Back 38

- Encodes a protein that binds to intracellular bacterial peptidoglycans and subsequently activates NF-κB

- Disease-associated NOD2 variants are less effective at recognizing and combating luminal microbes, which are then able to enter the lamina propria and trigger inflammatory reactions

- Other data suggest that NOD2 may regulate immune responses to prevent excessive activation by luminal microbes

Front 39

What is the mucosal immune response to bacteria in IBD?

Back 39

- Dendritic cells sample bacteria in lumen and present them to T cells on MHC
* Some T cells become TH1 cells, which release TNF
* TNF can lead to epithelial barrier defects which can cause an influx of bacterial components
* Some T cells can become TH17 cells (via IL-23)
- Additionally, some T cells can become TH2 cells, which release IL-13

Front 40

What epithelial defects have been described in Crohn's Disease and/or Ulcerative Colitis?

Back 40

- Defects in intestinal EPITHELIAL TIGHT JUNCTION barriers seen in CD and some of their healthy 1st-degree relatives
- Barrier dysfunction can activate innate and adaptive mucosal immunity and sensitize subjects to disease

Front 41

How does the microbiota relate to IBD pathogenesis?

Back 41

- Some antibiotics, such as metronidazole, can be helpful in maintenance of remission in Crohn disease by controlling the microbiota
- Ill-defined mixtures containing probiotic bacteria may combat disease in experimental models, as well as in some patients with IBD
- The mechanisms responsible are not well understood

Front 42

What is the most predominant, non-genetic factor in IBD?

Back 42

Colonizing bacteria:
- IBD is characterized by an amplified response to the intestinal microbiota
- Differences in microbiota composition and diversity may also contribute to IBD

Front 43

What are the types of disease behavior in Crohn's Disease? How common are they at DIAGNOSIS of CD?

Back 43

* Inflammatory: 85% (eg, erythema, ulcerations)
- Stricturing: ~0% (eg, blockage)
- Penetrating: 15% (eg, fistulas)

Front 44

What are the types of disease behavior in Crohn's Disease? How common are they 20 years after diagnosis of CD? Implications?

Back 44

* Penetrating: 70%
* Stricturing: ~20%
- Inflammatory: ~10%

Most patients end up requiring surgery d/t penetrating disease (fistulas) or stricturing disease

Front 45

What does this image represent? Which type of IBD is it associated with?

Back 45

- Fistula (can be between two loops of small intestine, or with the vagina, skin, peritoneum, etc)
- Sign of Crohn's Disease

Front 46

What are the new classes of drugs for treating IBD?

Back 46

Biologics: antibodies against TNF

Front 47

What are the Biologics used to treat IBD? Mechanism?

Back 47

Anti-TNF monoclonal antibodies:
- Infliximab
- Certolizumab pegol
- Adalimumab

Front 48

What are the benefits of anti-TNF therapy for IBD?

Back 48

- Induces and maintains remission of IBD
- Steroid sparing
- Heals perianal fistulizing disease

Front 49

What is the efficacy of anti-TNF therapy based on how long a patient has been diagnosed with IBD?

Back 49

The patients who have had a shorter disease time course were more likely to induce remission than those who had the disease for a longer period of time

Front 50

What are the side effects of anti-TNF therapy?

Back 50

Slight increase in incidence of lymphoma (however, the risk of lymphoma is very low compared to the risk that you will need surgery if you remain untreated)

Front 51

Why is there decreased rates of infection in patients with IBD?

Back 51

- Fewer patients on steroids now d/t anti-TNF therapy, therefore fewer opportunistic infections
- Improved mucosal healing
- Fewer fistulas, strictures, and abscesses

Front 52

What are the types of Microscopic Colitis?

Back 52

- Collagenous Colitis
- Lymphocytic Colitis

Front 53

What are the symptoms of Collagenous Colitis and Lymphocytic Colitis (types of microscopic colitis)?

Back 53

- Chronic, non-bloody, watery diarrhea without weight loss
- Findings on radiologic and endoscopic studies are normal

Front 54

What are the characteristics of Collagenous Colitis?

Back 54

- Type of microscopic colitis
- Presence of dense sub-epithelial collagen layer
- Increased numbers of intra-epithelial lymphocytes
- Mixed inflammatory infiltrate within lamina propria

Front 55

What are the characteristics of Lymphocytic Colitis?

Back 55

- Type of microscopic colitis
- Histologically similar to collagenous colitis
- Sub-epithelial collagen layer is of normal thickness and the increase in intra-epithelial lymphocytes may be greater
- Associated with celiac and auto-immune diseases

Front 56

Which type of microscopic colitis is associated with celiac and auto-immune diseases?

Back 56

Lymphocytic Colitis

Front 57

How do you treat Microscopic Colitis (both collagenous and lymphocytic)?

Back 57

Budesonide

Front 58

Why is the small intestine relatively sterile compared to the colon?

Back 58

- Protected by gastric acid
- Protected from bacteria in colon by ileocecal valve
- Relatively fast transit time

Front 59

What can cause increased bacterial contact with unabsorbed carbohydrates? Implications?

Back 59

- Surgery (eg, gastric bypass disrupts pH)
- Antacid
- Slow motility

- Can lead to small intestinal bacterial overgrowth

Front 60

How do you diagnose Small Intestinal Bacterial Overgrowth?

Back 60

- Duodenal aspirate
- Hydrogen breath test