Inflammatory Bowel Disease
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Transcript of Inflammatory Bowel Disease
Inflammatory bowel disease
It includes a group of chronic disorders that cause inflammation or ulceration in large and small intestines.
intestines.
Genetic factors
• Ulcerative colitis is more common in
DR2-related genes
• Crohn’s disease is more common in
DR5 DQ1 alleles
• 3-20 times higher incidence in first degree relatives
Other forms of IBD
• Collagenous colitis
• Lymphocytic colitis
• Ischemic colitis
• Behcet’s syndrome
• Infective colitis
• Intermediate colitis
Pathogenesis of IBD
American Gastroenterological Association Institute, Bethesda, MD.Sartor RB. Nat Clin Pract Gastroenterol Hepatol. 2006;3:390-407.
NormalGut
Tolerance-controlled
inflammation
Environmental trigger
(Infection, NSAID, other)
Acute Injury
Complete Healing
Chronic Inflammation
GeneticallySusceptible
Host
Acute Inflammation
↓ Immunoregulation,failure of repair or bacterial clearance
Tolerance
Pathology
Macrocopic features
• Ulcerative colitis
Usually involves rectum & extends proximally to involve all or part of colon.
Spread is in continuity.
May be limited colitis( proctitis & proctosigmoiditis)
in total colitis there is back wash ileitis (lumpy-bumpy appearance)
Microscopic features
Crypts atrophy & irregularity
Superficial erosion
Diffuse mixed inflammation
Basal lymphoplasmacytosis
Macroscopic features
• Crohn’s disease
Can affect any part of GIT
Transmural
Segmental with skip lesions
Cobblestone appearance
Creeping fat- adhesions & fistula
Microscopic features
• Aphthous ulcerations
• Focal crypt abscesses
• Granuloma-pathognomic
• Submucosal or subserosal lymphoid aggregates
• Transmural with fissure formation
IBD Is Not the Same as IBS
• IBD is sometimes confused with irritable bowel syndrome (IBS).
• The striking difference between the two diseases is that there is no identifiable inflammation in IBS.
• Some symptoms may be similar - abdominal pain, diarrhea,• but the other symptoms and signs of IBD are not seen -
bloody stools, fever, and weight loss. • The cause of IBS is believed to be dysfunction of the
intestinal muscles, nerves, and secretions and not inflammation.
• Signs of inflammation in the intestine as well as symptoms outside of the abdomen are not seen in IBS.
D/D of IBD?
Diagnosis
• Laboratory tests
• Endoscopy
• Radiography
• Biopsy
• CT enterography
Laboratory tests
• CRP-elevated
• ESR-elevated
• Anemia
• Leukocytosis
• hypoalbuminemia
Barium enema
String sign
Colonoscopy
CT enterography
• Mural hyperenhancement
• Stratification
• Engorged vasa recta
• Perienteric inflammatory
changes
Treatment
Treatment
Lifestyle changes
5-ASA Agents•Sulfasalazine (5-aminosalicylic acid and sulfapyridine as carrier substance) •Mesalazine (5-ASA), e.g. Asacol, Pentasa•Balsalazide (prodrug of 5-ASA)• Olsalazine (5-ASA dimer cleaves in colon)
Oral• Varies by agent: may be released in the distal/terminal
ileum, or colon1
Distribution of 5-ASA Preparations
Suppositories• Reach the upper rectum2,5
(15-20 cm beyond the anal verge)
Liquid Enemas• May reach the splenic flexure2-4
• Do not frequently concentrate in the rectum3
Topical Action of 5-ASA: Extent of Disease Impacts Formulation Choice
1. Sandborn WJ, et al. Aliment Pharmacol Ther. 2003;17:29-42; 2. Regueiro M, et al. Inflamm Bowel Dis. 2006;12:972–978; 3. Van Bodegraven AA, et al. Aliment Pharmacol Ther. 1996; 10:327-332; 4. Chapman NJ, et al. Mayo Clin Proc. 1992;62:245-248; 5. Williams CN, et al. Dig Dis Sci. 1987;32:71S-75S.
• Use In mild to moderate UC & crohn’s colitis Maintaining remission May reduce risk of colorectal cancer
• Adverse effects Nausea, headache, epigastric pain, diarrhoea,
hypersensitivity, pancreatitis Caution in renal impairment, pregnancy, breast feeding
Glucocorticoids
• Anti inflammatory agents for moderate to severe relapses.
• Inhibition of inflammatory pathways
• Budesonide- 9mg/dl used for 2-3 months & then tapered.
• Prednisone-40-60mg/day
• No role in maintainence therapy
Antibiotics
• No role in active/quienscent UC
• Metronidazole is effective in active inflammatory,fistulous & perianal CD.
• Dose-15-20mg/kg/day in 3 divided doses.
• Ciprofloxacin
• Rifaximin
Immunosuppresants
• Thiopurines
Azathioprine
6-mercaptopurin
• Methotrexate
• Cyclosporine
Cyclosporine
• Preventing clonal expansion of T cell subsets
• Use
Steroid sparing
Active and chronic disease
• Side effects
Tremor, paraesthesiae, malaise, headache, gingival hyperplasia, hirsutism Major: renal impairment, infections, neurotoxicity
Other medications
Anti- diarrheals - Loperamide (Imodium)
Laxatives - senna, bisacodyl
Pain relievers. acetaminophen (Tylenol).
Iron supplements
Nutrition
Surgery
Ulcerative colitis
Indications:
• Fulminating disease
• Chronic disease with anemia, frequent stools, urgency & tenesmus
• Steriod dependant disease
• Risk of neoplastic change
• Extraintestinal manifestations
• Severe hemorrhage or stenosis
Commonly observed ADR with agents used to treat IBD
Glucocorticoids
– Hyperglycemia, hypertension, osteoporosis, fluidretention and electrolyte, disturbances, myopathies,psychosis, and reduced resistance to infection,adrenocortical suppression
– Specific regimens for withdrawal of glucocorticoidtherapy have been suggested
Commonly observed ADR with agents used to treat IBD
Immunosuppressants
– Bone marrow suppression, and have beenassociated with lymphomas (in renal transplantpatients) and pancreatitis.
Infliximab
– Infusion reactions, serum sickness, sepsis, andreactivation of latent tuberculosis.
Commonly observed ADR with agents used to treat IBD
Sulfasalazine
– GI disturbances- nausea, vomiting, diarrhea, or anorexia
– Patients receiving sulfasalazine should receive oralfolic acid supplementation since sulfasalazine inhibitsfolic acid absorption
References
• http://demystifyingmedicine.od.nih.gov/DM12/2012-03-27/2012-03-27-Yao.htm
• http://www.slideshare.net/ParichiBuch/inflammatory-bowel-disease-10728466
• http://www.medicinenet.com/inflammatory_bowel_disease_ibd_pictures_slideshow/article.htm