Inflammatory Bowel Disease Flashcards
IBD
- Chronic intestinal inflammation from a dysregulated immune response to the enteric microbiome in a genetically predisposed host.
Pathogenesis of IBD
- Luminal microbial antigens and adjuvants
- Genetic susceptibility
- Immune response (exaggerated)
- Environmental triggers
IBD Epidemiology
- ~3.5 million in the US
- 7-10 per 100,000 IBD per year in US
average age of diagnosis: 11-12 years
IBD Genetics
- 50% concordance in identical twins
- CARD 15/NOD2 polymophisms on IBD1 locus
- SLC22A4 and SLC22A5 on IBD 5 loculs
- HLA-B, HLA-DRB1, HLA-DQB1, and HLA-DP, especially UC
- 6-9% of children born to a parent with UC and CD respectively, will develop IBD
- 33% affected if both parents with IBD
IBD Environment
-higher predisposition in norther latitudes
-microbes and flora (use of antibiotics predisposes)
-Smoking worsens Crohn’s but is protective for UC
- Appendectomy: risk for Crohn’s and protective for UC
Ulcerative Colitis versus Crohn’s
UC: Mucosal, Continuous.
Crohn’s: Transmural, discontinuous, oral to perianal. rectal sparing, non-caseating granulomas
Indeterminate Colitis: patchy colic disruption, histopathologic features of UC, 30-70% are diagnosed as CD or UC during the course of follow up.
Extraintestinal manifestations: Musculoskeletal
Type 1: <5 joints, larger joints, brief, associated with luminal activity.
Type 2: multiple small joints, independent of luminal activity
Ankylosing spondylitis (<2%), progressive sacroillitis: HLA B27
Osteopenia.
Digitial clubbing: particularly with small intestine involvement
Extra intestinal manifestations: other
Skin: pyoderma gangrenosum, erythema nodosum, cancer, ?acne
Hepatic: Autoimmune hepatitis, PSC
Renal: stones, obstructive uropathy (ileal disease/ileal resection: oxalate malabsorption)
Hematologic: hypercoagulability, thromboembolic events
Diagnosis:
- CBC, iron, TIBC, Ferritin
- Albumin and liver chemistries
- CRP/ESR
- Fecal calprotectin/lactoferrin
-serology: not recommended - Monitoring: above + therapeutic drug monitoring.
Exclusionary labs
- Celiac
-Stool infectious studies - TB/Amebic titers
- young kids: question immune competence
- vasculitis/multiple organs
Scope in Crohn’s disease
-EGD: upper GI system is usually spared, may see nonspecific esophagitis, gastritis, duodenitis
- Colonoscopy: skip lesions. loss of vascularity –> deep ulceration. Later: pseudopolyps
Scope in UC
Endoscopy:
Colonoscopy: pancolitis: 70-80%. Left sided: 20-30%, proctitis/proctosigmoiditis: 26%.
Can have non-classic findings: gastritis: 25-58%
backwash ileitis: 9%
Cecal path: small area of cecal inflammation after left sided disease: 9%
IBD Histology
- Cryptitis, crypt abscesses, gland destruction/branching/remodeling.
- acute and/or chronic inflammation
- granulomas in CD: 10-25%
IBD Imaging
- plain film: mural thickening, gas pattern (to exclude toxic megacolon)
- CT scan: transmural changes and complications
- MRE: same as above, but avoids radiation
- US: abscess and bowel hyperemia
Toxic megacolon
- NPO/antibiotics
- surgical consultation and careful follow up
-prevention with ambulation and avoid agents which slow motility (no opiates).
Steroid dosing
- Start a real dose with aggressive taper: no real advantage above 40-60 mg daily.
only induction, never maintenance. severe colitis: 3-5 day rule
Side effects: facies, striae, weight gain, moody, bone disease, growth failure. - Consider topical steroid enemas
Mesalamine
- MOA: inhibit prostaglandin and leukotriene synthesis.
- location of drug release dependent on formulation
- minimally absorbed
- Side effects: diarrhea (paradoxical reaction), headache, nausea, interstitial nephritis, pancreatitis, leukopenia and hepatitis.
- Monitor: CBC, liver chemistries, BUN, Cr, and UA
supplement folic acid with sulfasalazine
Antibiotics: Ciprofloxacin and Flagyl
- used in management of perianal disease
- short term post-op prophylaxis
- little pediatric evidence
Side effects: peripheral neuropathy (Flagyl). Bone/achilles tendon rupture (Ciprofloxacin).
Thiopurines: 6-MP and Imuran
- Immune modifier
- Use: maintenance of remission with and without biologic.
- Side effects: Nausea, Vomiting, DIarrhea, allergic reaction, BM suppression, hepatotoxicity, pancreatitis (idiosyncratic), infections, lymphoma (HSTCL), nonmelanoma skin cancer, HLH in EBV naive patients
Before starting: check vaccine acquired immunity
o: TPMT before initiating therapy. Ongoing: CBC and liver chemistries.
Methotrexate
- Immune modifier
- Use: maintenance of remission with and without biologic.
- MOA: not fully known ?T cell apoptosis.
Side effects: N/V, stomatitis, anorexia, diarrhea, BM suppression, hepatotoxicity, pneumonitis, hypersensitive skin reactions.
Monitor: CBC and liver enzymes.
Before starting: vaccine acquired immunity - Bad for pregnancy
Tacrolimus and Cyclosporine
- Calcineurin inhibitors
- Use: induction of remission in moderate to severe disease and perianal disease
- Side effects: HTN, Nausea, transaminitis, infection, nephrotoxicity, glucose intolerance, hypomagnesemia, seizures, infection, LPD.
Cyclosporine: gingival hyperplasia, hirsutism, coarsening facil features.
Monitor: Ca, MG, Phos, BUN/Cr, CBC, transaminases, lipids, cholesterol, fasting glucose, drug trough levels and PCP prophylaxis.
Anti-TNFalpha
induction and maintenance of remission.
UC: only infliximab is pediatric approved
Monoclonal IgG antibody to TNFalpha
Infliximab: chimeric and adalimumab: fully human.
Side effects: infusion reaction/allergy, infections (fungal, TB), lymphoma (HSTCL in combo with thiopurines) non-melanoma skin cancer, cytopenias, transaminitis, psoriasis, demyelination syndrome, lupus- like reaction, worsening CHF
Monitor: PPD/Quang gold, CXR, vaccine acquired immunity
Vedolizumab (antiadhesion)
Induction and maintenance of remission.
Monoclonal IgG1 antibody to alpha4 B7 integrin: inhibits lymphocyte migration across endothelium into inflamed bowel.
Side effects: headache, arthralgia, nausea, fever, fatigue, URI, ?PML
Monitor before starting therapy: PPD
Nutritional Therapy
- Induction (?maintenance? ) of remission in Crohn’s.
MOA: avoidance of allergenic food elements and alteration of intestinal microflora.
Ideally 80-100% caloric intake through formula. Elemental and polymeric formulas have equivalent efficacy
largely related to NGT, may have diarrhea
DDX of Perianal disease
- Sexual abuse
- Anal fissure (defecation disorders)
- Infections
- Hemorrhoids
- Prolapse
- Crohn’s disease
- Perianal strep
perianal abscess management
MRI and EUA to define the anatomic problem
surgery: get the pus out first.
Use setons as required to control sepsis.
treat proctitis/intestinal inflammation.
more definite surgical closer should be considered only after intestinal inflammation under control
Surgery in Crohn’s disease
- Transmural complications including abscess, perforation
- Obstruction
- Need for post-op surveillance
- Need for prophylaxis against recurrence
Surgery in UC
- acute severe colitis
- unresponsive disease
Crohn’s Outcome
59% have complicating disease by 5 years
Risk of surgery: 20% at 3 years and 34% at 5 years from diagnosis
