Inflammatory bowel disease intestines.It includes a group of chronic disorders thatcause inflammation or ulceration in large andsmall intestines.
TYPES Crohn’s disease Ulcerative colitis• Extends into the deeper layers of the intestinal wall, • causes ulceration and and may affect the mouth, inflammation of the inner esophagus, stomach, and lining of the colon and small intestine. rectum.• Transmural inflammation and skip lesions. • It is usually in the form of• In 50% cases -ileocolic,30% characteristic ulcers or open ileal and 20% -colic region. sores.• Regional enteritis
Other forms of IBD• Collagenous colitis• Lymphocytic colitis• Ischemic colitis• Behcet’s syndrome• Infective colitis• Intermediate colitis
Etiopathogenesis• Exact cause is unknown.• Genetic factors• Immunological factors• Microbial factors• Psychosocial factors
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
Immunologic factors• Defective regulation of immunesuppresion• Activated CD+4 cells activate other inflammatory cells like macrophages & B-cells or recruit more inflammatory cells by stimulation of homing receptor on leucocytes & vascular epithelium.
Pathogenesis of IBD Tolerance Acute Injury Environmental trigger Normal Complete Healing Gut (Infection, NSAID, other) Genetically Tolerance- Acute Inflammation Susceptible controlled Host ↓ Immunoregulation, inflammation failure of repair or bacterial clearance Chronic InflammationAmerican Gastroenterological Association Institute, Bethesda, MD.Sartor RB. Nat Clin Pract Gastroenterol Hepatol. 2006;3:390-407.
PathologyMacrocopic 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)
• Mild disease- erythema & sand paper appearance(fine granularity)• Moderate-marked erythema,coarse granularity,contact bleeding & no ulceration• Severe- spontaneous bleeding, edematous & ulcerated(collar button ulcer).• Long standing-epithelial regeneration so pseudopolyps , mucosal atrophy & disorientation leads to a precancerous condition.• Eventually can lead to shortening and narrowing of colon.• Fulminant disease-Toxic colitis/megacolon
Clinical features• Ulcerative colitisDiarrheaRectal bleedingTenesmusPassage of mucusCrampy abdominal pain
• Diarrhea & bleeding blood-intermittent &mild. do not seek medical attention.• Patient with proctatis-pass fresh or blood stained mucus with formed or semi formed stool. They also have tenesmus , urgency with feeling of incomplete evacuation.• With proctosigmoiditis-constipation• Severe disease-liquid stools with blood , pus & fecal matter.
• Physical signsProctitis – Tender anal canal & blood on rectal examinationExtensive disease-tenderness on palpation of colonToxic colitis-severe pain &bleedingIf perforation-signs of peritonitis
Clinical Severity of UC Mild Moderate Severe Fulminant Bowel movement <4 >6 >10 Blood in stool Intermittent Frequent Continuous Temperature Normal >37.5° >37.5° Pulse Normal >90 bpm >90 bpm Intermediate <75% normal Transfusion Hemoglobin Normal rate required ESR <30 mm/hour >30 mm/hour >30 mm/hour Abdominal Abdominal Clinical signs distension and tenderness tenderness1. Truelove SC, et al. Br Med J. 1955;2:1041-1045.2. Sandborn WJ. Curr Treat Options Gastroenterol.1999;2:113-118.
Laboratory tests• HemogramC-reactive protein is increasedESR is increasedPlatelet count-increasedHemoglobin-decreased Fecal Calponectin levels correlate with histological inflammation,predict relapses &detect pouchitis
5-ASA Agents•Sulfasalazine (5-aminosalicylicacid and sulfapyridine as carriersubstance)•Mesalazine (5-ASA), e.g. Asacol,Pentasa•Balsalazide (prodrug of 5-ASA)• Olsalazine (5-ASA dimer cleavesin colon)
Topical Action of 5-ASA: Extent of Disease Impacts Formulation Choice Distribution of 5-ASA Preparations Oral • Varies by agent: may be released in the distal/terminal ileum, or colon1 Liquid Enemas • May reach the splenic flexure2-4 • Do not frequently concentrate in the rectum3 Suppositories • Reach the upper rectum2,5 (15-20 cm beyond the anal verge)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
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
Biological therapy• Infliximab Anti TNF monoclonal antibody Infliximab binds to TNF trimers with high affinity, preventing cytokine from binding to its receptors It also binds to membrane-bound TNF- a and neutralizes its activity & also reduces serum TNF levels.• Use Fistulizing CD Severe active CD Refractory/intolerant of steroids or immunosuppression• Side effects Infusion reactions, Sepsis, Reactivation of Tb, Increased risk of Tb