Introduction to Inflammatory Bowel Diseases Flashcards
1
Q
IBD
A
o IBD is chronic or recurring inflammation of the GI tract due to dysregulated immune response
o IBD IS NOT THE SAME AS IBS!!
2
Q
prevalence of IBD
A
- Approximately 1.85M patients with IBD in US
- Slightly more UC > CD
3
Q
incidence of IBD
A
- Slight M > F in UC
- Slight F > M in CD
- Majority diagnosed young (15-35yo)
- Bimodal distribution with small bump in new diagnoses 60-70s yo (M>F in late UC dx, F>M in late CD dx)
4
Q
Ulcerative colitis
A
- Term first used in 1875 by Samuel Wilks and Walter Moxon to differentiate case of inflamed colon from infectious diarrhea
- Involves ONLY the colon
- Always involves the rectum, can involve the colon more proximally in a continuous fashion
5
Q
UC pathology
A
-Limited to mucosa and submucosa
6
Q
UC clinical manifestations
A
- Bloody diarrhea (Mucus, Frequency, Urgency, Tenesmus, Nocturnal bowel movements)
- Abdominal pain
- Constitutional symptoms (Fatigue, Anorexia, Weight loss)
7
Q
Chron’s disease
A
- Named after Dr. Burrill B. Crohn who published a landmark paper in 1932 describing the features of what is known today as Crohn’s disease
- Can affect ANY portion of the digestive tract from mouth to anus (Small bowel disease only: 30%, Ileocolonic disease: 40%, Colonic disease only: 30%, Upper GI tract: 0.5-4%, Perianal disease: 33% (5% anus only))
8
Q
chrons pathology
A
- Involves entire thickness (“transmural inflammation”)
- Will involve cobblestoning
9
Q
consequences of transmural inflammation
A
- Abscess
- Fistula – connecting from one space to another
- Stricture
- The inflammation breaks down the wall and the fecal matter goes to a different lumen
10
Q
Clinical symptoms of CD
A
- Highly variable depending on location of inflammatory process
- Colonic: can be similar to ulcerative colitis (Diarrhea, Blood in stool, Abdominal pain, Weight loss, weakness and anorexia)
- Small bowel (Diarrhea, usually non-bloody, Abdominal pain, Fever/weight loss/anorexia, Malabsorption/malnutrition, Stricturing – nausea, vomiting, bloating, food aversion, Perforating - FUO, Sepsis)
11
Q
risk factors for inflammatory bowel disease
A
- Heritability (One parent with UC = 2% chance of offspring with IBD, One parent with Crohn’s disease = 5%, Both parents with IBD = 36%, Monozygotic twin studies show 18% and 58% concordance in UC and CD, respectively)
- Race/Ethnicity (Ashkenazi Jewish and Caucasians vs Navajo Indians)
- Industrialization, urban areas, northern climates (Leading markets US (prevalence: 319/100,000) and Europe (322/100,000) vs China 1-2/100,000)
12
Q
geographic distribution of inflammatory bowel disease
A
- Rates highest in northern locales
- More common in Caucasians than in blacks
- Less common in Asians and Hispanics
13
Q
risk factors for inflammatory bowel disease
A
- Smoking (Increases risk of CD, Is PROTECTIVE in UC)
- NSAIDs
- ? Other medications (Accutane, OCPs)
- ? Appendicitis – children who had appendectomy may have reduced risk of UC but higher increased risk of CD
- ? Diet (high in animal protein)
14
Q
fecal microbiota are abnormal in IBD
A
- UC and CD fecal microbiota are distinct from each other as well as from infectious colitis and normal patients
- Depleted microbiome diversity has been demonstrated in both CD and UC
- Colonic microbiome contribute to multiple functions critical to health (Metabolism of insoluble carbohydrates, Vitamin / micronutrient production, Immune development and homeostasis, Ancillary mucosa protection)
15
Q
challenges to treating IBD
A
- Often fluctuating disease severity and disease “flares”
- Treatments don’t work for everyone
- Treatments that do initially work may stop working
- Drugs are expensive
- Drugs have side effects and safety concerns
- Patients may want to stop treatment
- No one-size-fits-all
16
Q
goals of therapy
A
- Improve clinical symptoms (Induce and maintain clinical remission)
- Decrease hospitalization/surgery
- Minimize disease and treatment-related complications
- Heal mucosal lesions
17
Q
factors influencing treatment
A
- Ulcerative colitis or Crohn’s disease
- Disease severity
- Anatomic location of disease
- Previous response to medications
- Side effects of medications
- Comorbidities
- Patient preferences
18
Q
pharmacologic treatments
A
- 5-Aminosalicylates (5-ASA)
- Immunomodulators (AZA, 6-MP, MTX)
- Biologics (Anti-TNF, Alpha-4, beta-7 integrin receptor antagonists)
- Corticosteroids
- Antibiotics
19
Q
5-aminosalicylates (5-ASA)
A
- Major drug in class is mesalamine
- Anti-inflammatory compounds
- Decrease inflammation in wall of intestine
- Can be given orally or rectally
- Generally very safe
- Primarily used for treatment of mild UC for induction and maintenance of remission
- Efficacy in Crohn’s disease is marginal (Mesalamine does not have an FDA indication for CD, Monotherapy can be considered for mild Crohn’s limited to the colon)
20
Q
immunomodulators
A
- Modifies activity of immune system to reduce ongoing inflammation
- Members: 6-mercaptopurine (6-MP), Azathioprine (AZA, prodrug of 6-MP), Methotrexate (MTX)
- Used in treatment of IBD for 40+ years
- Slow onset of action (~ 6 months)
21
Q
adverse effects of immunomodulators
A
- Infectious complications (7%): serious 2%
- Myelosuppression 5%
- Transaminase elevation 10% (dose-dependent)
- Lymphoma (1/2000)
- Increase in non-melanoma skin cancers
- Nausea/dyspepsia up to 20%
- Up to 20% discontinue due to AEs
22
Q
how anti-TNFs work
A
-A lot of the strategies are finding the molecule first and then finding something that will bind it
23
Q
Limitation of biologics
A
- 40% of primary responders lose response to the drug over time
- Loss of response (LOR) can be caused by accelerated clearance of the drug especially upon formation of antibodies against the drug
- Extremely expensive (>$15,000/year)
- Requires either self-injection or infusion
24
Q
TNF safety issues
A
- Tuberculosis reactivation
- Hepatitis B reactivation
- Reactivation of opportunistic infections
- Malignancy / lymphoma
- Neurologic events/ demyelination syndromes
- Cardiovascular events
- Deaths
25
Q
corticosteroids
A
- Prednisone continues to be the mainstay of treatment for patients with acute flares of IBD
- Multiple adverse effects associated with steroid use prevents use in maintenance
- Patients who are steroid-dependent should be started on biologics early on to prevent morbidity of chronic steroid exposure
26
Q
short-term adverse effects of prednisone
A
- Weight gain
- Fluid retention
- Sleep disturbance
- Mood swings
- Acne
27
Q
long-term adverse effects of prednisone
A
- Infection
- Bone loss / osteoporosis
- Cataracts / Glaucoma
- Skin fragility
- Hypertension
- Diabetes
28
Q
budesonide
A
- Glucocorticoid with high affinity for GI tract but low systemic activity due to extensive first-pass metabolism in the liver
- ”Prednisone lite”
- Less effective than prednisone but substantially fewer corticosteriod adverse events
29
Q
other treatment options
A
- Diet – Mediterranean diet, low FODMAPs diet
- Supplements – Tumeric!
- Marijuana?
- Fecal transplant?
- Helminth therapy?
- Surgery
