IBD more common in?
Western countries (USA & Europe).
Whites are affected more often than blacks.
Jewish origin are at higher risk.
bimodal: diagnosed between the ages of 20 - 40 or 60 - 80 years.
The incidence is 10 - 40 x greater in individuals with a 1st degree relative who has IBD compared with the general population.
Positive family history may be a contributing factor for development of CD than UC
Causes of IBD and factors involved?
cause of idb is unknown but it is belivd the inflammation is secondary to antigen immune response
factors
1. genetic predesposition
2. dysregulatioon of inflammatory reponse to git
3. environmental and antigenic factor
NSAID, Corticosteriod and smoking effect on IBD?
NSAID: that disrupt the integrity of the GI mucosa may facilitate mucosal entry of intestinal antigens and lead to IBD flares
corticosteroid: some studies suggest corticosteriod cause ibd but its not ptoven
smoking: smoking has protective effect for UC but harmful for CD Cause worsneing of symptoms
Ulcerative Colitis
inflammatory condition of the large intestine characterized by the availability of diarrhea that might be bloody
Characteristic
Incidence (per year)
Anatomical location
Distribution
Bowel wall
Non-caseating granulomas
Strictures
Toxic megacolon
Bowel carcinoma
Incidence uc: 6-12/100000 cd: 5-7/100000
location: uc- colon to rectum cd: mouth to anus
Distribution uc: continous, diffusal mucosal cd: focal, segmented, transmural
Bowel wall: uc: shorthened. cd: thick
Non-caseating granulomas uc: absent cd: present
Strictures uc: absent, cd present
Toxic megacolon : uc: occasional. cd: rare
Bowel carcinoma uc: greatly increase, cd: slight increase
Laboratory Findings
- leukocytosis
- decrease hematocrit and hemoglobin
- high CRP and ESR
- positive test of occult test
- Panca 70% in uc
- asca 50% in cd
(+) Perinuclear antineutrophil cytoplasmic antibodies
(+) Anti–saccharomyces cerevisiae antibodies
Ulcerative Colitis pathophysiology?
* proctitis
* proctosigmoiditis
* Pancolitis
The inflammatory response in UC is propagated by atypical type 2 helper T cells that produce the inflammatory mediators: IL-1, IL-6 & TNF-α
* proctitis: involve only rectum
* proctosigmoiditis: involve rectum and sigmoid colon
* Pancolitis:inflammation involve whole colon
crohne disease
chronic, transmural, patchy, granulomatous, inflammatory disease that can affect any part of the GIT. Small and large bowel involvement is most common
Pathophysiology Crohn’s Disease
- The inflammatory response in CD is propagated by type 1 helper T cells that produce the inflammatory mediators: TNF-α, interferon-γ, and IL-1, IL-6, IL-8, and IL-12
- TNF-α is the major contributor to the inflammatory process in CD.
1. include activation of macrophages
2. procoagulant effects in the vascular endothelium
3. increased production of matrix metalloproteinases in mucosal cells. - TNF-α is also induce production of nuclear factor kappa B (κβ) , which stimulates further production of TNF-α and other proinflammatory cytokines
- The pattern of inflammation in CD is discontinuous; areas of inflammation are intermixed with areas of normal GI mucosa, resulting in characteristic “skip lesions.”
non pharmacological treatment
Dietary Recommendations: no restriction on diet avoid high residue food high fiber like whole grain, fruits etc. with stictures to prevent obstruction, avoid dietry fat.
nutritional Strategies:: take some vitamin and mineral like vitamin b12, folic acid, iron to prevent deficiencies
In severe cases, enteral or parenteral nutrition may be needed to achieve adequate caloric intake.
surgical Intervention: ulcerative colitis, total colectomy can be curative, Patients with CD may resection (removal) of affected areas of the intestine
Surgical intervention is an option in patients with complications such as fistulas or abscesses, or in patients with medically refractory disease.
some medications not use in ibd
anti diarrhea: operamide, diphenoxylate, and codeine, reduce (GI) motility, avoided due to the risk of precipitating acute colonic dilation (toxic megacolon).
anticholnergic: hyoscine used for spasm and pain, reduce gi motility and avoided
Opioids: reduce gi mortility and avoided due to risk of colonic dilation
NSAID: avoided bcz they worsen symptoms and inflammation
Patients who have had multiple intestinal resections due to CD may have diarrhea related to the inability to reabsorb bile salts. Cholestyramine may improve diarrheal symptoms in these patients.
Aminosalicylates
* use
* MOA
* route of admin
* delivery mechansim
* adv effects
use: for induction and maintaince of remission for mild/ moderate ibd
MOA: 5asa (mesalamine and mesalazine) delivery to inflammed area of git where they have antinflammatory properties
route of admin: oral and rectal: rectal is use for proctitis and disease localize to distal colon
delivery mech: 5 asa is either linked to carrier or alter the ph of git effected site to relase formulation
adv effects: dose dependent adv effect limit aptine tolerability,
The prototypical aminosalicylate is sulfasalazine
which is 5-ASA linked by a diazo bond to sulfapyridine. Once sulfasalazine reaches the colon, bacterial degradation of the diazo bond frees 5-ASA from sulfapyridine. Sulfapyridine is then absorbed and excreted renally while 5-ASA acts locally within the GI tract.
corticosteroid
use:
short/ long term
dose
topical steoris
tapering dose
use: for moderate to severe acute flare ups in ibd they have anti inflammatory effect
short/long term: corticoteriod improv symtoms and severity but only use for short term induction. its not used for remission long term use has side effects
dose: oral 40-60mg prednisolone, iv: hydrocortisone 300mg, methylprednisolone: 40-60mg daily
topical steorid ( suppository, enemas, foams for distal colotis)
Guidelines recommend budesonide for active disease because it has low systemic bioavailability.
immunosuppresent
azthiopirine or 6MP Agents targeting the immune response or cytokines, used in dose depended corticosteroid
methotrxate use in CD when 6mp not work
cyclosporin use in UC when corticosteorid not work
Use in active disease is limited by their slow onset of action, which may be as long as 3 - 12 months.
Disadvantages of anti-TNF biologic agents:
- The need for parenteral administration
- The potential for serious adverse effects e.g. lymphoma
- High drug cost
- Antibodies may develop to infliximab over time that may reduce its efficacy and predispose patients to development of infusion-related adverse effects.
Mild to Moderate Active UC:
- first-line therapy involves oral or topical aminosalicylates or oral budesonide.
- Topical mesalamine is superior for inducing remission in mild to moderate UC.
- Oral mesalamine may be used if unable to use topical preparations.
- Combination of oral and topical mesalamine can be used for maximal effect.
- Topical corticosteroids are reserved for non-responsive cases.
Proper education on topical product use is crucial for efficacy.
Moderate to Severe Active UC
- oral corticosteroid for short term of patient not responsive to aminosylate
- predisolone 40-60mg day recommended
- azithioprine or 6mp is used to corticosteroid non responsive patient or depended
- biologic also responsive to patient non responsive to oral therapies
- azithroprine + alixomab to increase effect
Severe or Fulminant UC:
- hospitalization required for severe symptoms.
- IV corticosteroids if unresponsive to other oral therapies
- Infliximab or adalimumab options for severe cases.
- Anti TNF-α are not indicated for fluminant uc
- Surgery considered for significant systemic toxicity or colonic dilation in fluminant uc
Maintenance of Remission in UC:
- Up to 50% of patients receiving oral therapies and up to 70% of untreated patients relapse 1 year
Oral or topical aminosalicylates for maintenance.Rectal aminosalicylate for proctitis or left-sided disease.
Corticosteroids not effective for maintenance and should be avoided.
Immunosuppressants and biologics used for unresponsive patients or corticosteroid dependency.
Mild to Moderate Active CD:
budesonide or aminosylate for mild/ moderate cd
budesonide 9mg daily for 8 weeks, beneficial for terminal ilum or ascending colon
conventional corticosteroid : prednisolone , methylpred, more effective but have higher s.e
aminosylate: use may be less efficacy but used in patients with ileal, ileocolonic, or colonic CD
- Induction of remission may require up to 16 weeks of treatment at full doses
Moderate to Severe Active CD
- moderate to sever active: prednisolone 40-60mg
- moderately active and location is terminal ilum, and ascending colone, budisonide 9mg daily
- Anti TNF-α to non responsive to corticosteroid
- azithroprine +Anti TNF-α for enchanced effect
Severe to Fulminant Active CD
hospitalization require
surgery for complication like: masses, obstruction, abcess
iv corticosteroid prednisolone 40-60mg
biologics for severe cd not for fluminant
electrolyte and nutritional balance ( paternal eternal for patient not eaten 5-7 days)
Maintenance of Remission in CD
- 80% of patient experience replase within 2 yrs require maintaince
- immunosupressent and biologics are used for maintainces
- corticostroid cannot be used due to s.e and 50% of patient become dependent
- aminosylate less effective success rates of only 10% - 20% in 1 year
- azithroprine and tnf@ combine useful
*
Budesonide 6 mg orally once daily may be used in place of conventional corticosteroids
for up to 3 months after induction of remission in mild to moderate CD or in patients dependent on corticosteroids.
