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

Ulcerative colitis

Ulcer

pseudopolyps

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