What do we need for diagnosis of IBD

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What do we need for diagnosis of IBD Kaichun Wu Dept. of Gastroenterology, Xijing Hospital Fourth Military Medical University Xi an an,, China

In China UC 11.6/10 5,CD 1.4/10 5 Major cause of chronic diarrhea

olonic cancer 7.9% IBS 11.0% Ischemic colitis 4.9% Hemorroids 4.7% Others 4.2% IC 67.3% Misdiagnosed Cases of IBD U C C D Rate(%) 32.1 60.9 Appendicitis 27.9% Others 14.6% Intestinal TB 30.8% Obstruction 26.7%

What do we need for diagnosis of IBD Knowledge/experience Consensus/guideline New technologies

Consensus/guidelines of IBD in the West 2001 2004 ACG ACG CD practice guidelines UC practice guidelines 2006 ECCO CD consensus management

Consensus management of IBD in China by IBD Collaborative Group in CSG published in Chin J Gastroenterol 2007 2 parts(diagnosis and treatment), 4 units, 19 sections, 15 pages in total

Diagnosis of ulcerative colitis Clinical criteria:intestinal, extraintestinal Endoscopic criteria:distal, diffuse, continuous Radiologic criteria:less important Histologic criteria:superficial

Clinical presentation of UC Intestinal symptoms: chronic diarrhea(bloody) abdominal pain (crampy) urgency of defecation

Clinical presentation of UC Extraintestinal manifestations: erythema nodosum, pyoderma gangrenosum, aphthous ulcer, uveitis, iritis, arthritis, arthralgia, osteoporosis hepatitis, primary sclerosing cholangitis

Colonoscopic appearance in UC 1)Losing vascular transparency, edematous, fragile, fibrin 2)Erosion, bleeding, ulceration 3)Reduced haustration, pseudopolyps, mucosal bridge

Histology of ulcerative colitis Mucosal biopsy: 1)Epithelial inflammation, crypt abscess 2)Crypt irregular, distorted glands, chronic infiltration 3)Acute and chronic inflammation

Radiologic appearance in UC Ba enema: 1)Irregular, granular mucosa 2)Ulceration, filling defect 3)Bowel shortened, haustration lost

Diagnostic criteria of ulcerative colitis Chronic course(>4-6 weeks) Typical symptoms suspicious Symptoms + endoscopic/ba enema(1) provisional Symptoms + endoscopic/ba enema(1) + histologic(1) confirmed Atypical or firstly diagnosed 3-6 months follow-up Endoscopic colitis ulcerative colitis Chin J Gastroenterology, 2007

Truelove and Witts classification of UC* * Moderate is between the mild and severe Diarrhea Bleeding Temperature Pulse Hb ESR Mild <4 /day intermittent normal normal normal <30mm/h Severe >6 /day frequent >37.5 ( C) >90/min <75% >30mm/h

Southerland DAI (Mayo index) Score 0 1 2 3 Diarrhea No >1~2/day >3~4/day >5/day Bleeding No little much mainly blood Mucosal No fragile fragile very fragile & exudation Doctor s evaluation No mild moderate severe Total score<2 remission;3~5 low ;6~10 moderate;11~12 high activity

Diagnosis of Crohn s disease Clinical criteria:intestinal, perianal disease Radiologic:segmental, stricture, fistula, longitudinal ulcer Endoscopic:skip, stricture, longitudinal ulcer, cobble stone Histologic:granuloma with non-caseation, fissure ulcer Surgical: transmural, asymmetric, skip, stricture

Crohn s disease Fistula Fistula fistula and abscess Peri-anal disease CD

Crohn s disease radiography

Pale Edema Stenosis Bleeding Ulceration Cobble stone Crohn s disease colonoscopy CD

Granuloma Fissure ulcer UC Crohn s disease histology

UC Bowel resection specimens Crohn s disease CD

Diagnostic criteria of Crohn s disease Chronic course(>4-6 weeks) Typical symptoms suspicious Symptoms + SBFT/endoscopic provisional Symptoms + SBFT/endoscopic + histologic(1-3) confirmed Atypical or firstly diagnosed 3-6 months follow-up Differentiating intestinal TB 4-8 weeks diagnostic therapy Chin J Gastroenterology, 2007

WHO recommended CD diagnosis Clinical radiologic endoscopic histologic surgical Segmental + + + Longitudinal ulcer, cobble stone + + + Transmural + mess + stricture + stricture + Granuloma, non-caseative + + Fissure ulcer, fistula + + + Perianal lesions + + + *1. 1+2+3=suspicious ; 2. 1+2+3+4or5or6=confirmed ; 3. 4+ two of 1or2or3 =confirmed

Best CDAI Variants Power Diarrhea(1week) Abdominal pain(1week) Overall(1week) extraintestinal(1 for 1item) Opinin Abdominal mess Sedimentation(normal:M47,F42) 100 (1-bwt/standard) Total=sum of V 2 5 7 20 30 10 6 1 CDAI<150 remission; >150 active, 150~220 mild, 220~450 moderate, >450 severe

Differentiation between IBD and acute self limiting colitis (ASLC) Clinical course Onset Diarrhea Stool culture IBD chronic, recurrent gradual, no fever <6/day no pathogen ASLC <4 weeks started with fever >10/day pathogen in 50% Plt elevated Crypt structure Cell infiltration 59% cases distorted neutrophil in LP fewer,~1.6% intact plasma cell in base of crypt

Differentiation between UC and CD UC CD Location distribution Complications Stricture Cancer risk Endoscopy Gross specimens colon continuous, diffuse mucosal rare fistula rare,central ++++ edematous,fragile mucosa granular,hyperplastic polyps any parts of GI tract segmental, skip lesions transmural common fistula or abscess common,asymmetric ++ aphathous ulcer,cobble stone sign, longitudinal ulcer terminal ileum lesion(30%),segmental lesions,stricture/fistula/perianal lisions(75%) Histology crypt abscess, no granuloma transmural,submucosal thicken, granuloma(45%)

Endoscopic difference between UC and CD UC CD Location left colon right colon rectum>95% rectum<50% T. ileum rare common Distribution diffuse, continuous asymmetric, skip Mucosal ulcer irregular ulcer longitudinal, deep hyperemia, erosion around normal mucosa around exudation common rare bleeding common rare peudopolyps common rare cobble stone rare common

Differentiation between CD and intestinal tuberculosis CD IC-TB TB in other place no yes Perianal yes no Fistula common rare Ulceration longitudinal circumferential Histology non-caseative granuloma, mesentric lymphonodes caseative granuloma Anti-TB therapy no effect effective in 4~8 weeks

Differentiation between intestinal tuberculosis and CD in endoscopic biopsy specimens by PCR Positive rate(%) CD 0 IC-TB 64.1 71.4(granuloma+) 61.1(granuloma -) Histology non-caseative granuloma caseative granuloma Gan HT, et al. Am J Gastroenterol. 2002

Innovative diagnostic procedures

Serologic markers (1)CRP (2)ESR (3)platlets;albumin;sialic acid;aag;fibrinogen;lactoferrin; β2-microglobulin ; amyloid A ; α2-globulin ; α1anti-typsin ; OMP-C ; 12-peptide (4) panca for UC 60%~80% ASCA for CD 60%~70% Combination 87%~97% (ASCA bacterial-driven antibody marker) Useful for indeterminate colitis

Faecal markers Calprotectin(Cal ), lactoferrin(lf ), lysozyme, elastase, myeloperoxidase (1)calprotectin(Cal) (2)lactoferrin(Lf) Correlate well with CRP, ESR, disease activity and severity

CROHN S COLITIS SUBGROUPING Segmental STRICTURING Oct 1996, Barium enema 2003, CT Colonography

IBD related cancers Start at 5~8 years from onset Malignancy in 20 years 10%~20% Correlate with disease extension, site, duration Pancolitis prominent and early Long history prominent UC malignancy multi-foci Difficult to find by endoscopy/barium enema Mucosal biopsy may help Genetic study helpful

Endoscopic developments 1. Chromocolonoscopy 2. Confocal laser endomicroscopy 3. Narrow band imaging colonoscopy 4. Endocytoscopy 5. Wireless capsule endoscopy 6. Double-balloon enteroscopy

Chromocolonoscopy for UC

Mild UC UC in remission

Confocal laser endomicroscopy

Narrow Band Imaging Allows better detection of vessels and small mucosal lesions 415nm 445nm 500nm 540nm 600nm 400 450 500 550 600 nm

Endocytoscopy