Clinical Presentation of IBD Flashcards
What is important regarding the pathophysiology as it relates to treatment for IBD?
- there is increased permeability within the tight junctions allowing pro-inflammatory cytokines to be activated (mainly TNF-a).
- circulating T cells with integrin-a4B7 bind to endothelial cells increasing entry of gut specific T cells.
Does decreased physical activity and obesity increase your risk for Crohn’s disease?
YES
How does ulcerative colitis present clinically?
- diarrhea (often bloody), frequent but small volume
- urgency
- colicky abdominal pain
- gradual and progressive onset
- in moderate to severe disease= fever, pallor, tenderness, and muscle wasting
Do most patients with ulcerative colitis present with mild disease?
YES= less than 5 stools/day, no systemic toxicity, and mild crampy pain.
What are the lab/imaging findings for acute ulcerative colitis?
- anemia
- elevated sed rate (always elevated for inflammation)
- low albumin
- electrolyte abnormalities
- elevated fecal calprotectin (BEST)
- p-ANCA
- thickened bowel wall on CT
- loss of haustra on barium swallow
How do you basically diagnose ulcerative colitis?
- exclude other causes (history, labs…)
- diarrhea greater than 4 weeks + active inflammation on colonoscopy + chronic changes on biopsy
What will you see on a colonoscopy for ulcerative colitis?
- loss of vascular markings (engorgement)
- erythema, granularity
- petechiae, exudates, edema, erosions, friability
- pseudopolyps
- profuse bleeding
- ALWAYS involves RECTUM and proceeds proximally in a circumferential pattern.
Do we always biopsy the ileum in IBD?
YES to help us discern whether it is Ulcerative colitis or Crohn’s disease
Do patients with just proctitis (inflammation of the rectum) have a more benign course in ulcerative colitis?
YES
What is the goal with treatment of ulcerative colitis?
heal the mucosa, thus decreasing the risk of colectomy (removal of colon).
What are the complications of ulcerative colitis?
- toxic megacolon (greater than 5 cm)= increased colonic diameter with systemic toxicity. This can lead to perforation (50% mortality).
- benign strictures (MALIGNANT mass until proven otherwise).
- dysplasia/colorectal cancer (highest risk in pancolitis).
What are the extraintestinal manifestations of ulcerative colitis? (see printout)
- PRIMARY SCLEROSING CHOLANGITIS= inflammation of intra and extra hepatic bile ducts leading to cholestasis (look for beaded strictures of bile ducts on ERCP). Independent of disease activity.
- ankylosing spondylitis (more in Crohn’s; independent of disease activity)
- peripheral arthritis (independent of disease activity)
- osteopenia/osteoporosis
- pyoderma gangrenosum (independent of disease activity).
- aphthous stomatitis (canker sores)
- sweets syndrome=sudden onset of fever, leukocytosis, and tender, red, well-demarcated papules and plaques (not specific to IBD).
- increased risk of venous thromboembolism
- hemolytic anemia
- uveitis (independent of disease activity)
- episcleritits
- erythema nodosum (more in Crohn’s)
Does treatment of IBD affect the course of primary sclerosing cholangitis?
NO
*you could take out the entire colon and you would still have primary sclerosing cholangitis.
Does primary sclerosing cholangitis increase your risk for colon cancer?
YES. Therefore you must get a colonoscopy every 1-2 years when you have this.
Is there a cure for IBD?
NO
What are the 2 goals for managing IBD?
- induce remission
2. maintain remission
What is mesalamine (5-ASA)?
- oral medication used ONLY for IBD, developed to prevent proximal absorption via ph and time dependence along with a colonic bacteria requirement for activation. Works by inhibitings pro-inflammatory cytokines, cause immunosuppression, free radial scavenger, and impairs leukocyte function.
- topical formulation via enema exists as well.
- used only for mild-moderate ULCERATIVE COLITIS (sometimes for crohn’s).
Does mesalamine reach past the splenic flexure?
NO
What is Azathioprine?
- rapidly metabolized to 6-mercaptopurine (6-MP), which inhibits proliferation of B and T cells, and causes apoptosis of T cells.
- TPMT (thiopurine S-methyltransferase) will convert 6-MP to an inactive metabolite. Thus TPMT must be measured in all pts prior to starting this drug.
If a pt has homozygous non-functional alleles for TPMT, can you use azathioprine?
NO
If a pt has heterozygous non-functional alleles for TPMT, can you use azathioprine?
YES but decrease the dose
What do we use to monitor drug levels of azathioprine?
6-thioguanine (6-TGN) to measure for toxic effects.
When is azathioprine used?
in pts who have steroid refractory UC and Crohn’s disease
*takes 6 months to take effect (usually used in combination with other drugs)
** What is a side effect of azathioprine? (TEST QUESTION)
hepatosplenic T cell lymphoma
What is Methotrexate?
folic acid analogue that inhibits dihydrofolate reductase. It somehow helps with maintenance of remission in Crohn’s disease but we don’t know how.
What is Cyclosporine A?
- inhibits calcineurin to block transcription of cytokine genes in T cells. Induces remission in ACUTE SEVERE STEROID REFRACTORY ULCERATIVE COLITIS.
- rapid onset (1-2 weeks) but only used short-term.
What are the side effects of cyclosporine A?
infections, seizures, low cholesterol, nephrotoxicity, and neuropathy
What are the biologics?
inhibitors of TNF-alpha (this is the new craze)
- infliximab (used for both UC and crohn’s)= chimeric (mouse/human) and therefore we can mount an antibody response to it; IV infusion every 8 weeks.
- adalimumab (used for both UC and crohn’s)= fully human and less likely to form antibodies agains it; SQ injection every 2 weeks.
What are the side effects of the biologics (TNF-alpha inhibitors)?
- infections (latent TB or hepatitis B)
- malignancies (RARE)
- heart failure
- cutaneous (viral or bacterial infection)
- demyelinating disease
What is Vedolizumab?
- newest integrin receptor antagonist that is a humanized immunoglobulin against alpha-4-beta 7 integrin. This inhibits trafficking of lymphocytes and its action is confined to the GI tract.
- used for induction/maintenance of remission in REFRACTORY UC and CROHN’S.
What is the advantage of Vedolizumab over the TNF-alpha inhibitors?
no known risk of major infection or malignancy
What is oral prednisone or IV solumedrol or topical rectal hydrocortisone?
- corticosteroids used ONLY to INDUCE REMISSION in UC and Crohn’s.
- safe to use in pregnancy
What are the side effects of corticosteroids?
psychosis, anxiety, HTN, salt retention, muscle wasting, weight gain, hyperglycemia, osteoporosis, and infection risk.
** What steroids do we use more now?
intraluminal steroids that remain longer in the GI tract.
- Budesonide is used for mild-moderate CROHN’S in the ileum and proximal colon
- Budesonide-MMX is for delivery to the entire colon in mild-moderate UC.
- side effects are rare due to 90% first past metabolism.
Can antibiotics be used in Crohn’s?
rarely but can sometimes be used (bacterial overgrowth or Clostridum difficile).
What are the basic principles for managing acute IBD symptoms? (remember IBD is a chronic disease with acute flare ups)
- determine if symptoms are really from IBD
- determine outpatient vs impatient
- rule out complications (not everyone needs imaging)
- bowel rest if severe symptoms (NPO then clears, then low fiber).
- IV fluid if hospitalized
- determine if colonoscopy will change management
- continue maintenance medication
- add medication for induction (steroids most common)
What is the first line INDUCTIVE treatment for mild-moderate ulcerative proctitis/proctosigmoiditis (aka ULCERATIVE COLITIS)?
- topical 5-aminosalicylic acid (5-ASA) or suppository or enema depending on location.
- if this doesn’t work, add a rectal steroid, followed by an oral steroid if that doesn’t work.
What is the MAINTENANCE treatment for mild-moderate ulcerative proctitis/proctosigmoiditis (aka ULCERATIVE COLITIS)
- nothing if 1st episode and you had a prompt response to inductive therapy.
- if you relapse, then 5-ASA (mesalamine) and/or rectal 5-ASA.
What is the INDUCTION therapy for mild-moderate left-sided/extensive colitis, pancolitis (aka ULCERATIVE COLITIS)?
oral + topical 5-ASA
*if no response add rectal steroid, followed by oral budesonide-MMX if that fails.
What is the MAINTENANCE treatment for mild-moderate left-sided/extensive colitis, pancolitis (aka ULCERATIVE COLITIS)?
- oral 5-ASA +/- topical 5-ASA
* can’t do rectal steroids long term
What is important to remember about oral steroids (prednisone)?
must taper gradually
What is steroid DEPENDENT UC?
- unable to taper prednisone below 10 mg or they relapse within 3 months
What is the initial management for severe/fulminant colitis (aka ULCERATIVE COLITIS)?
- oral prednisone + high dose oral 5-ASA + topical 5-ASA/steroid
- discontinue anticholinergics, antidiarrheals, NSAIDS, and opiates
- if they don’t respond, hospitalize and give them IV steroids.
How do you treat severe/fulminant UC that is steroid REFRACTORY in the hospital?
- anti-TNF (infliximab)
- cyclosporine to transition to azathioprine (similar to steroid dependent).
- colectomy
Are corticosteroids for short term use only?
YES
How do you treat steroid DEPENDENT (can’t taper steroids to less than 10 mg) UC patients?
- azathioprine/6-MP for maintenance
- OR- add IV cyclosporine to transition more quickly to azathioprine.
- if they do not respond, go to colectomy.
What surgery can be done for pts who do not respond to medical therapy for UC?
- proctocolectomy with ileal pouch-anal anastomosis
What is chromoendoscopy?
- stains or pigments (blue) sprayed during colonoscopy to improve tissue location when looking for dysplasia/colorectal cancer
How is CROHN’S DISEASE classified (vienna classification)?
- inflammatory= just inflammation
- stricturing= inflammation with narrowed lumen (either inflammatory; can treat medically, -OR- fibrotic; requires surgery).
- penetrating (fistulizing)= inflammation with abnormal communication between bowel and other structures.
What is a phlegmon/abscess that occurs due to CROHN’S DISEASE?
- phlegmon= walled off inflammatory mass w/o infection.
- abscess= + infection, localized peritonitis.
What is perianal disease (associate with CROHN’S DISEASE)?
- pain and drainage from large skin tags, anal fissures, perirectal abscesses, or anorectal fistulas.
** What are the unique extraintestinal manifestations for CROHN’S DISEASE?
- renal stones (calcium oxalate)
- bone loss/osteoporosis
- B12 deficiency
Will you see perianal disease in crohn’s or UC?
ONLY CROHN’S
How do we diagnose CROHN’S?
- if abdominal pain= imaging
- if diarrhea= colonoscopy
- anti-saccharomyces cerevisiae antibody (ASCA), CRP, and fecal calprotectin are also used.
Why is management of CROHN’S DISEASE so much different than management of UC?
bc we use the BIG GUNS first for CROHN’S, whereas we start lightly with UC and work our way up.
What is the management for mild-moderate CROHN’S DISEASE?
- oral 5-ASA
- antibiotics if no response
- oral steroids if no response.
What is the management for refractory/severe CROHN’S DISEASE?
- azathioprine/6-MP
- methotrexate
- biologics (vedolizumab)
Should you give steroids to a pt with fistulas or localized peritonitis from CROHN’S?
NO bc these are infectious and steroids will make it worse.
*treat with antibiotics instead.
How do you treat an abscess due to CROHN’S?
antibiotics and drain.
Is the risk of colorectal cancer higher or lower in Crohn’s vs UC?
lower than UC
