Term
A patient presents with painless diarrhea and bleeding with "fresh appearing blood."
On PE, you find pale mucosal membranes and orthostatic hypotension, but no pain on abdominal palpation.
How do you confirm your diagnosis and what common complications of this disease worry you? |
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Definition
Ulcerative Colitis (inflammation/ulceration confined to mucosa, always involving rectum and spreading contiguously proximally to involve a variable portion of the colon as well).
Painless diarrhea and Hematokezia are classic UC, and pale mucosal membranes (anemia) and orthostatic hypotension (dehydration) are characteristic PE findings.
1) Diagnosis
- Run stool tests to rule out infectious (salmonella, shigella, C. jejuni, EHEC) and drug-induced (NSAID) causes
- Endoscopy/Colonoscopy should show "wet sandpaper," diffuse granularity of mucosa, erythema, friability and spontaneous bleeding.
- Biopsy shows inflammatory infiltrate within mucosa, crypt abscesses and fewer goblet cells
2) Complications
- bleeding with anemia
- Toxic megacolon/perforation*****
- growth delay
- cancer with stricture formation (less common in CD) |
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Term
An 18 year old male patient presents with abdominal pain, fever, abdominal distention and diarrheal bleeding with "fresh appearing blood." They appear "toxic."
What is going on? |
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Definition
| Toxic megacolon complicating Ulcerative Colitis |
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Term
What % of crohn's disease patients have
1) Only small bowel disease
2) Ileocolonic disease
3) Colonic limited |
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Definition
All have transmural inflammation in patchy distribution.
1) 35% have only small bowel
2) 45% have ileocolonic
3) 20% have Colitis |
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Term
A young woman presents with fatigue, abdominal pain (right lower quadrant), weight loss, fever and diarrhea.
On PE, the patient has orthostatic hypotension and you palpate an abdominal mass. You also note high pitched bowel sounds, indicating an obstruction.
How do you definitely diagnose this condition and what are the common complications? |
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Definition
Sounds like Crohn's disease (transmural inflammation with patchy distribution in small bowel and/or colon)
1) Diagnosis
- Colonoscopy/Endoscopy (Serpiginous" ulcers, pseudopolyps, "cobblestone" appearance of mucosa, strictures)
- Biopsy shows transmural inflammation (instead of mucosal as in UC)
- GRANULOMA is pathognomoic but only present in 50%
- Radiographic tests include barium swallow ("string sign" of strictures, CT ("creeping fat") and MRI, and are often necessary.
2) Complications
- Fibrostenoic strictures with obstructive symptoms.
- Cancer is rare |
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Term
| What are the common extra-intestinal manifestations of IBD? |
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Definition
1) Arthritis
- peripheral arthritis "flares" with IBD "flares
- central arthritis does not correlate
2) Eye inflammation
- Uveitis/painful
3) Skin lesions
- Erythema nodosum: red, raised lesions on lower extremeties
- Pyoderma gangrenosum
4) Oral lesions
5) Vascular complications
- Autoimmune hemolytic anemia and thrombotic disease
6) Primary sclerosing cholangitis
- Progressive inflammation, fibrosis and destruction of intra and extra hepatic bile ducts, resulting in cirrhosis and portal htn.
- Occurs in 5% of UC (less common in CD)
- 75% of people with PSC have IBD
- Associated with HLA-DRw52a and HLA-B8 and p-ANCA
- Course does NOT parallel IBD |
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Term
| What is the importance of Primary sclerosing cholangitis? |
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Definition
Progressive inflammation, fibrosis and destruction of intra- and extra- hepatic bile ducts, resulting in cirrhosis and portal HTN.
1) Occurs in 5% of UC (less common in CD)
2) 75% of people with PSC have IBD
3) Associated with HLA-DRw52a and HLA-B8 and p-ANCA
4) Course does NOT parallel IBD |
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Term
| What are the major genetic associations with IBD? |
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Definition
CD is more heritable than UC
1) Several HLA associations
2) Chromosomal linkages
- IBD1- chromosome 16 (CD)
- IBD2- chromosome 12q (UC)
- IBD3- chromosome 6p (CD)
- IBD4- chromosome 14q (CD)
3) Genes
- NOD2 mutations at IBD-1 locus (CD) associated with inappropriate innate immune responses to normal bacteria (LPS), with decreased NF-kb response, decreased defensin 5 production by paneth cells and an exaggerated adaptive immune response. |
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Term
| What does NOD2 have to do with IBD? |
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Definition
1) Mutations in NOD2 on chromosome 16 (IBD-1 locus) associated with CD.
2) Mutations lead to inappropriate innate immune responses to normal bacteria (LPS), with decreased NF-kb response, decreased defensin 5 production by paneth cells and ultimately an exaggerated adaptive immune response.
3) Adaptive response leads to tissue damage in CD
**Only 10% of individuals with mutation actually get CD!** |
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Term
| What evidence argues for an infectious component of IBD pathogenesis? |
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Definition
IBD does not follow simple mendelian inheritance and there is not a 100% concordance in monozygotic twins.
1) Specific associated pathogens
- M. paratuberculosis, Measles, Listeria, H. hepaticus.
2) Putative role of "normal" enteric bacteria present in all people
- defective mucosal barrier in IBD |
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Term
| What is the role of smoking in IBD? |
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Definition
Protects against UC, but hurts CD.
However, people with UC don't smoke usually and those with CD do! |
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Term
| What is the current thinking on the immunological basis of IBD? |
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Definition
Abnormal immune response in genetically susceptible individual.
1) Overabundance of Th1 cells and lack of Th2 cells
- Imbalance between inflammation (TNF-a, IFN-y and IL-12) and anti-inflammation (IL-4,5, 10 and 13) |
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Term
| What are the 5 main categories of treatment for IBD? |
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Definition
Surgery works to cure UC and treat CD
1) 5-aminosalicylates (anti-inflammatory for UC>>CD)
- interfere with AA production by affecting thromboxane and lipoxygenase synthesis
- example is Sulfasalazine
2) Corticosteroids (anti-inflammatory and immunosuppressive for both UC and CD)
- Induce but NOT MAINTAIN remission
3) Antibiotics (Inhibit chemotactic peptides in CD only)
- Metronidazole (Flagyl) for pre- and post-operative CD maintenance.
- Cipro is also good alternative, but not in children
- Rifaximin (XIfaxan) works only on GI tract, and may be most specific.
4) Immunomodulators
- Azathiprine/6-mercaptopurine for CD (MOST) and steroid-dependent UC (inhibit ribonucleotide synthesis and prevent activated lymphocyte proliferation), but can cause transient PANCREATITIS
- Methotrexate (parenteral) inhibits dihydrofoltate reductase and purine synthesis in treatment of CD, with shorter onset of action than Azothioprine/6-MP (TERATOGEN!)
- Cyclosporine (IV lipophillic peptide for severe UC) has incredibly short onset of action (days) and inhibits proliferation and activation of Th cells by interfering with IL-2 production (if you give with other immunomodulators/steroids, treat Pneumocystis prophylactically!)
5) Biologics
- Anti-TNFa (Infliximab, adalimumab and certolizumab)
- ANti-adhesion agent (Natalizumab) |
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Term
| What drugs are available to treat CD, specifically? |
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Definition
Surgery can be curative and Antibiotics/Biologics will not work.
5-ASA, Steroids, Cyclosporine,
1) 5-aminosalicylates (anti-inflammatory for UC>>CD)
- interfere with AA production by affecting thromboxane and lipoxygenase synthesis
- example is Sulfasalazine
2) Corticosteroids (anti-inflammatory and immunosuppressive for both UC and CD)
- Induce but NOT MAINTAIN remission
3) Immunomodulators
- Cyclosporine (IV lipophillic peptide for severe UC) has incredibly short onset of action (days) and inhibits proliferation and activation of Th cells by interfering with IL-2 production (if you give with other immunomodulators/steroids, treat Pneumocystis prophylactically!) |
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Term
| What drugs are available to treat CD, specifically? |
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Definition
Surgery for symptoms and 5-ASA does not work as well as for UC.
1) Corticosteroids (anti-inflammatory and immunosuppressive for both UC and CD)
- Induce but NOT MAINTAIN remission
2) Antibiotics (Inhibit chemotactic peptides)
- Metronidazole (Flagyl) for pre- and post-operative CD maintenance.
- Cipro is also good alternative, but not in children
- Rifaximin (XIfaxan) works only on GI tract, and may be most specific.
3) Immunomodulators
- Azathiprine/6-mercaptopurine for CD (MOST) and steroid-dependent UC (inhibit ribonucleotide synthesis and prevent activated lymphocyte proliferation), but can cause transient PANCREATITIS
- Methotrexate (parenteral) inhibits dihydrofoltate reductase and purine synthesis in treatment of CD, with shorter onset of action than Azothioprine/6-MP (TERATOGEN!)
4) Biologics
- Anti-TNFa (Infliximab, adalimumab and certolizumab)
- Anti-adhesion agent (Natalizumab) |
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Term
| How does Cyclosporine differ from Methotrexate and Azothioprine/6-MP in terms of drug action? |
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Definition
Lipophillic peptide that inhibits IL-2 production and used for severe UC
Onset is within DAYS.
Remember, if you give as combination with azathioprine or 6-MP and steroids, you better treat opportunistic infections (Pneumocystis) prophylactically! |
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Term
Which of the following should be avoided during pregnancy for IBD treatment?
1) Methotrexate
2) Cyclosporine
3) Azathioprine
4) 6-mercaptopurine |
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Definition
1) Methotrexate is a teratogen (it inhibits dihydrofolate reductase and purine synthesis, decreasing inflammatory cytokine production).
All are immunomodulators (1,3 and 4 are for CD and 2 is for UC)
- Cyclosporine inhibits IL-2 and if given in combination with other immunomodulators and steroids, Pneuomocystis should be treated prophylactically.
- Azathioprine and 6-MP are useful in CD (T cell and NK cell suppression), and can cause transient pancreatitis. |
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Term
| Why might you prescribe Sulfasalazine? |
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Definition
To treat UC>>CD
- Inhibits lipoxigenase and thromboxane synthesis, modulating AA production and decreasing inflammation.
- Remember to supplement with folic acid
- Can be given topically for distal UC |
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Term
| When and what antibiotics can be used in IBD treatment? |
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Definition
Inhibit chemotactic peptides in CD
1) Metronidazole (Flagyl) for pre- and post-operative CD maintenance.
2) Cipro is also good alternative, but not in children
3) Rifaximin (XIfaxan) works only on GI tract, and may be most specific. |
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Term
Which of the following describes the action of cyclosporine in treating UC?
1) Inhibits dihydrofolate reductase and purine synthesis (decreasing inflammatory cytokine production)
2) Inhibits ribonucleotide synthesis and decreases lymphocyte proliferation
3) Inhibits IL-2 production and T-cell activation
4) Inhibits AA production and Lipoxygenase synthesis |
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Definition
3
1) Methotrexate (Teratogen)
2) Azathioprine/6-MP (Transient Pancreatitis)
4) 6-ASA (Sulfasazaline) |
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Term
Which of the following describes the action of Methotrexate in treating UC?
1) Inhibits dihydrofolate reductase and purine synthesis (decreasing inflammatory cytokine production)
2) Inhibits ribonucleotide synthesis and decreases lymphocyte proliferation
3) Inhibits IL-2 production and T-cell activation
4) Inhibits AA production and Lipoxygenase synthesis |
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Definition
1
2) Azathioprine-6MP (transient pancreatitis)
3) Cyclosporine (prophylactic treat of Pneumocystis when in combination with other immuno-modulators)
4) 5-ASA |
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Term
| What biologics are used to treat CD and how do they each work? |
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Definition
- Anti-TNFa (Infliximab, adalimumab and certolizumab) ALL teratogenic
- Anti-adhesion agent (Natalizumab)
1) Infliximab (Remicade)
- chimeric (human/murine) monoclonal Ab against TNF-a for CD not responding to standard therapy
- well-tolerated, but watch for opportunistic infections
2) Adalimumab (Humira)
- humanized anti-TNF is sub-q
- Also acts as IgG1 antibody
3) Certolizumab pegol (Cimzia)
- pegylated monoclonal Ab (prevent rapid renal clearnce)
- No IgG backbone, so no complement-mediated cell lysis
4) Natalizumab (Tysabri)
- humanized IgG4 Ab targeting integrin (a4 or a4b7) on leukocytes and preventing trafficking of white cells to MadCAM-1 or VCAM-1 expressing endothelial cells.
- Secondary treatment if Anti-TNF fails. |
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Term
| What surgical options are available for IBD? |
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Definition
1) UC (medication-refractory or complications)
-Permanent ileostomy or ileal pouch anal anastomosis
- Curative and eliminates chance of developing colorectal cancer.
2) CD
- Treats complications (fibrostenoic stricture with bowel obstruction or internal fistula) in 50-80% (NOT CURE)
- Partial intestinal resection
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Term
Which of the following is NOT correct?
1) Crohn's disease can occur anywhere in the GI tract
2) Ulcerative colitis is usually continuous and always involves the rectum.
3) Surgery is curative for Ulcerative colitis
4) Smoking is detrimental in Crohn's disease
5) Risk of colon cancer is higher in Crohn's than UC |
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Definition
5- UC has a higher colon cancer risk
1) Crohn's does occur anywhere, while UC is only in large bowel
2) UC is continuous, while Crohn's is skip lesions with or without the rectum (always the terminal ileum)
3) Surgery is curative for UC and treats complications in CD
4) Smoking is protective for UC and detrimental for CD |
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Term
Which of the following is NOT correct?
1) Ulcerative colitis is limited to the mucosa
2) Crohn's disease complications usually involve strictures and fistula
3) Crohn's is treated with Corticosteroids and 5-ASA agents
4) Smoking is protective in Ulcerative colitis
5) Crohn's disease often affects the terminal illeum. |
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Definition
3) Crohn's is treated with corticosteroids, immunomodulators and biologics, while UC is treated with 5-ASA and steroids.
1) UC is mucosa, CD is transmural
2) CD has strictures/fistula that require surgery/UC does not
4) Smoking protects against UC but hurts CD
5) Crohn's hits terminal illeum and UC always hits rectum |
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