IBD Pathophysiology Flashcards
Describe the epidemiology of Crohn’s disease: Prevalence, geography, sex, age
Prevalence: 26-200/100k (Rising)
Higher prevalence in Northern lattitudes
Even F:M ratio
Dx between 15-30 with another peak in 50-60s
Describe the epidemiology of Ulcerative Colitis: geography, prevalence, age of onset, sex
North-south gradient
Rates of UC are stable
Age of onset similar
Even incidence between sexes
Describe the function of NOD2. What is its significance
NOD2 recognizes bacterial MDP and binds peptidoglycans. It then up regulates NF-kB and MAPK signaling to modulate inflammation
What is evidence for the role of microbiome in IBD? (4)
IBD does not occur in germ-free environment
Some pts with CD develop Ab to enteric flora proteins
Most common locations of CD are ileum/colon, where bacteria levels are highest
Abx appear to have potential benefit for some
Which immune cell types are involved in IBD?
There is dysregulation of both Th1 and Th2- mediated response
Which environmental factors are related to IBD? (4)
High SES
Dietary factors
Smoking: increases risk of CD; protective in UC
Stress
What are goals of therapy in IBD?
Improvement in QOL, induce remission, avoid surgery, mucosal healing
Which forms of IBD are “curable”?
UC can be cured with colectomy. Crohn’s is not curable
What factors warrant more aggressive early therapy? (5)
Tobacco use (for Crohn’s)
Perianal or penetrating disease
Requirement for steroids
Age
What are recommended therapies for mild disease? (4)
Short course of glucocorticoids for initial induction of remission
5-ASAs for UC
Budesonide for CD
Topical steroids for distal disease
What are recommend therapies for moderate to severe disease?
Immunomodulators: thiopurine antimetabolites and methotrexate
Biologics: anti-TNF, anti-alpha4, anti-cell signaling molecules
What are different preparations of melamine that have been developed? (4)
pH dependent systems
Diazo-bonded systems with bacterial release
Osalazine (double 5-ASAs)
Belsalazide (inert carrier)
What is MOA of ASAs?
Anti-inflammatory==>inhibition of T cell proliferation, antigen presentation, leukocyte adhesion, decreased TNF production
What is use for ASAs? What are AEs? (2)
Beneficial in UC, not in Crohn’s.
AEs: Paradoxical diarrhea, interstitial nephritis
What is clinical use for glucocorticoids in IBD?
Mainstay in induction of remission, but not useful in maintenance of remission
What are AE associated with glucocorticoid use? (long list)
Neuropsychiatric, Cushingoid, myopathy, glucose intolerance, infection, wound healing, hirsutism, bon effects, hypertension
What is budesonide? What are the reasons for its use?
Novel steroid compound with ileal or colonic release formulations.
High degree of first-pass lessens system side effects
Standard initial therapy
What is MOA of immunomodulators?
Both azathioprine and 6MP inhibit DNA synthesis
What is role of TPMT polymorphism in azathioprine/6MP?
1/300 have a reduced TPMT activity==>shunts AZA/6MP to an active metabolite 6-TGN, which markedly increases side effects
Describe the use and efficacy for thiopurines
Induction and maintenance of remission of CD
Reduces steroid utilization
What are AE of thiopurines? (5)
Leukopenia/marrow suppression Pancreatitis Drug-induced hepatitis Infection Malignancy
What is mechanism of methotrexate?
Described its efficacy
Folate antagonist that carriers anti-inflammatory properties
It’s effective in induction/maintenance of remission in Crohn’s; being evaluated for UC
What are AE of methotrexate? (6)
Nausea Hepatic fibrosis Teratogenic Marrow suppression Infection Pneumonitis
What is mechanism of anti-TNF therapy?
Bind soluble/cell-bound TNF-a and inhibit.
Induce apoptosis of T cells and lymphocytes in lamina propria
Alter cyotkine secretion in serum
What is approved use for anti-TNF therapy?
Induction and maintenance of remission in Crohn’s and UC
What are AE for anti-TNF therapy? (4)
Transfusion reactions or delayed hypersensitivity reactons
Drug-induced lupus
Infection
Malignancy
What is the use for anti-alpha4 inhibitors?
Natalizumab– benefit for MS also induction and maintenance of remission in Crohn’s
What is major risk of natalizumab? How is it managed?
Increased risk of progressive multifocal leukoencephalopathy.
Screen for JC virus
What is advantage of vedolizumab?
No PML risk
Approved for use in both CD/UC
