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Inflammatory bowel disease
It includes a group of chronic disorders that cause inflammation or ulceration in large and small intestines.
intestines.
TYPES
Crohn’s disease
• Extends into the deeper layers of the intestinal wall, and may affect the mouth, esophagus, stomach, and small intestine.
• Transmural inflammation and skip lesions.
• In 50% cases -ileocolic,30% ileal and 20% -colic region.
• Regional enteritis
Ulcerative colitis
• causes ulceration and inflammation of the inner lining of the colon and rectum.
• It is usually in the form of characteristic ulcers or open sores.
Other forms of IBD
• Collagenous colitis
• Lymphocytic colitis
• Ischemic colitis
• Behcet’s syndrome
• Infective colitis
• Intermediate colitis
Epidemiology
Ulcerative colitis Crohn’s
Incidence / 1 lac. 2.2-14.3 3.1-14.6
Age of onset 15-30, 60-80
Ethnicity Jewish
Male: Female 1:1 1.1-1.8 : 1
Smoking May prevent Causative
Oral contraceptives No risk 1.4 odds ratio
Appedicectomy Protective Not
Monozygotic 6% 58%
Dizygotic 0% 4%
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
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)
• Mild disease- erythema & sand paper appearance(fine granularity)
• Moderate-marked erythema,coarsegranularity,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
Microscopic features
Crypts atrophy & irregularity
Superficial erosion
Diffuse mixed inflammation
Basal lymphoplasmacytosis
Crypt
distortion
Diffuse inflammation
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
Granuloma
Aphthous ulcer
Clinical features
• Ulcerative colitis
Diarrhea
Rectal bleeding
Tenesmus
Passage of mucus
Crampy 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 signs
Proctitis – Tender anal canal & blood on rectal examination
Extensive disease-tenderness on palpation of colon
Toxic colitis-severe pain &bleeding
If perforation-signs of peritonitis
Mild Moderate Severe Fulminant
Bowel movement <4
Intermediate
>6 >10
Blood in stool Intermittent Frequent Continuous
Temperature Normal >37.5° >37.5°
Pulse Normal >90 bpm >90 bpm
Hemoglobin Normal<75% normal
rate
Transfusion
required
ESR <30 mm/hour >30 mm/hour >30 mm/hour
Clinical signsAbdominal
tenderness
Abdominal
distension and
tenderness
1. Truelove SC, et al. Br Med J. 1955;2:1041-1045.2. Sandborn WJ. Curr Treat Options Gastroenterol.1999;2:113-118.
Clinical Severity of UC
Diagnosis
• Laboratory tests
• Endoscopy
• Radiography
• Biopsy
Laboratory tests
• Hemogram
C-reactive protein is increased
ESR is increased
Platelet count-increased
Hemoglobin-decreased
Fecal Calponectin levels correlate with histological inflammation,predict relapses &detect pouchitis
Barium enema
Barium enema
• Fine mucosal granularity
• Superficial ulcers seen
• Collar button ulcers
• Pipe stem appearance-
loss of haustrations
• Narrow & short colon-
ribbon contour colon
Sigmoidoscopy
• Always abnormal
• Loss of vascular patterns
• Granularity
• Friability
• ulceration
Extra intestinal manifestations
Clinical features
• Ileal Crohn’s Disease
Abdominal pain
Diarrhea
Weight loss
Low grade fever
• Jejunoileitis disease
Malabsorption
Steatorrhea
Colitis and perianal disease
• Bloody diarrohea
• Passage of mucus
• Lethargy
• Malaise
• Anorexia
• Weight loss
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
Drugs
• 5-ASA agents
• Glucocorticoids
• Antibiotics
• Immunosuppresants
• Biological therapy
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
Biological therapy
• Infliximab Anti TNF monoclonal antibodyInfliximab binds to TNF trimers with high affinity, preventing cytokine from binding to its receptorsIt also binds to membrane-bound TNF- a and neutralizes its activity & also reduces serum TNF levels.
• UseFistulizing CDSevere active CDRefractory/intolerant of steroids or immunosuppression
• Side effectsInfusion reactions, Sepsis, Reactivation of Tb, Increased risk of Tb
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
Others
• Proctocolectomy & ileostomy
• Rectal &anal dissection
• Colectomy with ileorectal anastomosis
• Ileostomy with intraabdominal pouch
Crohn’s disease
• Ileocaecal resection
• Segmental resection
• Colectomy & ileorectal anastamosis
• Temporary loop ileostomy
• Proctocolectomy
• Stricturoplasty
Strictureplasty