INFLAMMATORY BOWEL DISEASE (IBD) Flashcards
Definition
A group of chronic systemic disease involving inflammation of the intestine:
- Crohn’s disease
- Ulcerative colitis
- Indeterminate colitis: shows features of both CD and UC
- Microscopic colitis: no macroscopic inflammation (lymphocytic type or collagenous type)
Etiology (3)
Interaction of 3 cofactors:
1- Genetic susceptibility:
- Stronger for CD than UC
- HLA- B27 —> IBD with ankylosing spondylitis
- CARD15 (N0D2) gene mutation in chrom.16 - ileocecal small bowel CD
- Increased concordance in monozygotic twins and familial clustering
- Family history is the largest independent risk factor for IBD
2- Environment:
- Smoking: exacerbates CD and increase its recurrence after surgery - in contrary there is increased risk of UC in non/ex-smokers
- NSAIDs: associated with both onset and flares of IBD
- Breastfeeding: provides protection against IBD in offspring
- Appendectomy: protective against UC
- Stress and depression: associated with relapses of IBD
- Crowded conditions with less hygiene —> lower risk of CD
3- Immune response of the host: in genetically susceptible person, there is an increased immune response to luminal antigens e.g. bacteria
Crohn’s Disease- Location (4)
- Can affect the whole GI tract (mouth to anus)
- Commonest region involved is iliocecal - 40%
- Rectal sparing is a typical but not constant feature of CD
- Oral and perianal involvement is common
Crohn’s Disease- Macroscopic Pathology (2)
- Discontinuous involvement “skip lesion”
- Deep ulcers and fissures in mucosa “cobblestone appearance”
Crohn’s Disease- Microscopic Pathology (3)
- Transmural patchy inflammation affecting all 3 layers
- Non-caseating granulomas present in 50%
- Lymphoid hyperplasia
Crohn’s Disease- Clinical Features (5)
- Major symptoms: diarrhea, abdominal pain, weight loss
- Constitutional symptoms: malaise, lethargy, nausea, vomiting, and low-grade fever (15% without GI symptoms)
- Type of diarrhea depends on site involved (steatorrhea if small bowel, bloody if colon)
- Anal/perianal disease may be the presenting feature in 25%. Manifested as tags, fissures, fistula, absesses
- May present as an emergency with right iliac fossa pain mimicking appendicitis and when laparotomy is taken, terminal ileum appears red and edematous
Crohn’s Disease- Physical Examination
- May be normal or may show aphthous ulcers* in the mouth, abdominal tenderness, mass (inflamed loops of bowel, abscess), anal tags, fissures, perianal abscesses
Note: extraintestinal manifestations should be assessed:
- Eyes: uveitis, episcleritis, conjunctivitis
- Joints: arthalgia, arthritis, ankylosing spondylitis, back pain
- Skin: erythema nodosum*, pyoderma gangrenosum (necrotizing ulceration of the skin, commonly on lower legs)
- Hepatobiliary: fatty liver, sclerosing cholangitis, chronic hepatitis, cirrhosis, gallstones
- Renal calculi (oxalate stones): interferes with bile acid absorption and so increase oxalate absorption
- Venous thrombosis
- * features related to disease activity
Ulcerative colitis- Location (3)
- Affects the colon only, starts from the rectum and extends proximally in varying degrees
- May affect the rectum alone (proctitis) or extends proximally (left-sided or extensive colitis)
- May have backwash ilieitis (inflammation of the distal ileum)
Ulcerative colitis- Macroscopic Pathology (3)
- Continuous involvement
- Red mucosa, bleeds easily
- Ulcers and pseudopolyps (regenerating mucosa) in severe disease
Ulcerative colitis- Microscopic Pathology (5)
- No granulomata
- Superficial, limited to mucosa
- Goblet cell depletion
- Crypt abscesses
- Chronic inflammatory cells in lamina propria
Ulcerative colitis- Clinical Features (4)
- Major symptom: diarrhea with blood and mucus +/- lower abdominal pain
- May present with constitutional symptoms, but not as severe as in CD
- Proctitis manifests as tenesmus and urgency together with bloody mucoid diarrhea
- Toxic megacolon
- Serious complication (due to risk of perforation)
- Colon is dilated, >6cm and occasionally up to 15cm on supine X-rays
- Supportive therapy (ICU monitoring, fluid resuscitation and correction of laboratory abnormalities, administration of broad-spectrum antibiotics, complete bowel rest, and a surgical consultation)
- IV corticosteroids
- IV Infliximab (if no response)
- Surgery (subtotal colectomy and ileostomy) if no response
Ulcerative colitis- Physical Examination
- May show either normal findings or abdominal tenderness and distention (? toxic megacolon)
- Pyrexia and tachycardia indicate severe colitis —>admission
Note: extraintestinal manifestations should be assessed:
- Eyes: uveitis, episcleritis, conjunctivitis
- Joints: arthalgia, arthritis, ankylosing spondylitis, back pain
- Skin: erythema nodosum*, pyoderma gangrenosum (necrotizing ulceration of the skin, commonly on lower legs)
- Hepatobiliary: fatty liver, sclerosing cholangitis, chronic hepatitis, cirrhosis, gallstones
- Renal calculi (oxalate stones): interferes with bile acid absorption and so increase oxalate absorption
- Venous thrombosis
- * features related to disease activity
Investigations (11)
1- Blood test: anemia (could be of chronic disease “normocytic normochromic”, iron deficiency “microcytic”, or folate/B12 deficiency “macrocyclic”)
2- In acute disease: low serum albumin, high platelets, ESR, and CRP
3- Liver biochemistry may be abnormal
4- Stool tests and C.difficile toxin: to exclude other causes of infective colitis. (Yersinia entercolitica is a great mimicker of CD and appendicitis)
5- Colonoscopy: definitive diagnosis, biopsy for nature of the inflammation and extent/severity of the disease
6- Small bowel barium follow-through (deep ulceration and narrowing “string sign”)
7- Video capsule endoscopy: more sensitive than barium study, increasingly used (contraindicated if stricture is suspected or found)
8- US/MRI: for perianal Crohn’s disease (esp. MRI)
9- U/S and CT: to evaluate abscesses, will show thick bowel in involved areas
10- Abdominal X-ray: in acute attacks to exclude colonic dilatations and perforations
11- Radiolabeled white cell scanning: safe and non-invasive but lacks specificity
Crohn’s Disease Management (2)
Initial/Induce remission:
- Oral/IV corticosteroid (oral prednisolone, reduced gradually over 8 weeks)
- Budesonide is of benefit in ileocecal CD. Steroid with extensive first pass mechanism —> therapeutic benefit with reduced systemic toxicity
- Aminosalicylates (less efficacious than in UC, only used in very mild disease)
- Antibiotics: metronidazole and ciprofloxacin in severe perianal disease (anti-bacterial and immunosuppressive)
Maintain remission:
- Azathioprine (AZA), mercaptopurine (6-MP)
- Side effects: acute pancreatitis, BM suppression, allergic reaction
- In AZA and MP, the key enzyme is thiopurine methyl transferase (TPMT). Deficiency of TPMT —> bone marrow suppression. Assay of TPMT activity must be performed before treatment
- Methotrexate is used in the minority resistant to treatment
- 3 months blood count is important to screen for bone marrow suppression as methotrexate also can cause bone marrow suppression
- Anti TNF agents (e.g. Infliximab): can be used as induction/maintenance, for perianal disease, and in patients not responding to immunosuppressive therapy
Ulcerative Colitis Management (5)
1- Mainstay for mild to moderate disease is 5-ASA e.g. sulfasalazine (rectal for proctitis and oral for left-sided/extensive colitis)
2- Oral predinoslone may be given as second line if inadequate response to 5-ASA
3- Severe disease: oral prednisolone or biological treatment with anti TNF agent
4- Severe and systemic: Hydrocortisone, cyclosporine, or anti-TNF alpha
5- Maintain remission with 5-ASA. If relapses are frequent add azathioprine or 6-MP
