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