Histopathology in Inflammatory Bowel Disease DR. RISH K. PAI

ASSOCIATE PROFESSOR OF PATHOLOGY

MAYO CLINIC ARIZONA

What is the goal of UC therapy? Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE): Determining Therapeutic Goals for Treat-to-Target. Am J Gastro 2015:110:1325

• In general, there is good correlation between endoscopy and histology

• 263 biopsies were taken from 131 patients with ulcerative colitis

Mayo score 0 Mayo score 1 Mayo score 2 Mayo score 3

Any histologic activity

14% 51% 93% 100%

Ulcers/erosions 0% 14% 20% 68%

Correlation between Endoscopic and Histologic Score in Assessing the Activity of UC Lemmens et al. Inflamm Bowel Dis 2013:19:1194-1201

Endoscopy does not tell the whole story

• Histology is more sensitive than endoscopy at detecting disease activity

• BUT… does histologic activity in the setting of normal endoscopy mean anything?

Study Endoscopic evaluation Histologic active disease

Truelove and Richards 1956 Normal sigmoidoscopy 37%

Lemmens 2011 Mayo score 0 14%

Bessissow 2012 Mayo score 0 40%

Bryant 2016 Baron score ≤ 1 27%

Baars 2012 Normal endoscopy 33%

• 15 patients experienced relapse of UC

• CRP was slightly elevated in relapsers (p=0.045)

• Use of biologics were somewhat protective of relapse (p=0.083)

Prognostic value of serological and histological makers on clinical relapse in UC patients with mucosal healing Bessissow et al. Am J Gastroenterol 2012:107:1684-92

Does Histologic Activity Predict Relapse? Bessissow et al. Am J Gastroenterol 2012:107:1684-92

• 74 patients with clinical and endoscopic inactive UC

*

Clinical, Biological, and Histologic Parameters as Predictors of Relapse in UC Bitton et al. Gastroenterology 2001:120:13-20

• 91 patients with UC ◦ Clinical activity (SCCAI)

Remission 0-2

◦ Endoscopic activity (Baron) Remission: 0-1

◦ Histologic activity (Truelove and Richards) Remission: No significant inflammation

Histologic Remission Better Predicts Corticosteroid Use and Hospitalization over 6 years of follow-up Bryant et al. Gut 2016:65:408-14

Variable Corticosteroid requirement Hospitalization for severe colitis Colectomy

Disease extent n.s. 3.21, p=0.02 4.06, p=0.02

Histologic remission 0.42, p=0.02 0.21, p=0.02 0.36, p=0.22

Endoscopic remission 0.86, p=0.65 0.83, p=0.74 0.71, p=0.64

Histo and Endo Remission 0.38, p=0.02 0.24, p=0.04 0.46, p=0.39

Bryant et al. Gut 2016:65:408-14

• 418 UC patients enrolled in surveillance, 15 advanced neoplasia

• Histologic inflammation measured using Gupta/Harpaz index

• Mean histologic inflammation score: HR 3.8 (adjusting for # scopes)

Histologic Activity and Neoplasia

Gupta et al. Gastroenterology 2007:133:1099-1105

Rutter et al. Gastroenterology 2004:126:451-9

• Case control study (68 cases of neoplasia, 136 controls)

• Colonoscopy scored 0-5, Histology scored 0-4

• Univariate: Colonoscopy score OR 2.54, Histology score OR 5.13

• Multivariate: Only histologic score, OR 4.69

The Case for Histopathology

• More sensitive at detecting disease activity than colonoscopy

• Strong predictor of disease relapse

• Predicts requirement for corticosteroids better than endoscopy

• Predicts hospitalizations for severe colitis better than endoscopy

• Predicts development of colorectal neoplasia better than endoscopy

Cochrane Review: Histologic Scoring Indices for Evaluation of Disease Activity in Ulcerative Colitis

The index needs to be reproducible, valid, and responsive to therapy

Mosli M, Bhandari A, Nelson SA, et al.

5986 records identified

56 records from other sources

3471 records after duplicates removed

3471 records screened

3345 records excluded

126 full text articles assessed

122 reports of 27 scoring systems excluded with reasons

4 reports of 2 scoring systems included

10 validated or partially validated indices out of 32 indices

Scoring index Validity Reliability Responsiveness Feasibility

Content

validity

Criterion

validity

Construct

validity

Inter Intra TR IC

1 Chicago/Rubin/Histologic

Inflammatory Activity

(HIA) Scale

+

?

+ ? ? ? ? ?

?

2 Geboes Score + + + ? ? ? ? ? ? 3 Gomes Index + ? ? ? ? ? ? ? ? 4 Harpaz Index + + + ? ? 5 Modified Harpaz Index + + + ? ? 6 Modified Riley Score + + + ? ? ? ? ? ? 7 Nancy Index + + + + ? 8 Riley Score + + + ? ? ? ? ? ?

9 Robarts Histopathology

Score (RHI) + + + + ?

10 Simplified Geboes Score + + + ? ? ? ? ? ?

+ positive rating ? no information or unclear rating - negative rating Inter = interrater Intra = intrarater TR = test-retest IC = internal consistency

Cochrane Review: Histologic Scoring Indices for Evaluation of Disease Activity in Crohn’s Disease Novak G, Parker CE, Lacey C, et al.

3520 records identified

3 records from other sources

2572 records after duplicates removed

2572 records screened

2466 records excluded

106 full text articles assessed

105 reports of 71 scoring systems excluded with reasons

1 report of 1 scoring system included

1 validated or partially validated indices out of 72 indices

+ positive rating ? no information or unclear rating - negative rating

Inter = interrater Intra = intrarater TR = test-retest IC = internal consistency

Scoring index Validity Reliability Responsiveness Feasibility

Content

validity

Criterion

validity

Construct

validity

Inter Intra TR IC

1 Naini 2012 + ? ? + ? ? ? ? ?

Conclusions

•

46 year old man

4 week history of: Bloody diarrhea 5-10x daily Abdominal cramps Weight loss 5 kg

WBC 12.1 x 109/L

Hgb 115 g/L

ESR 38

Negative: Stool culture Ova and parasites C. difficile

Left-sided colitis

Case 3: Histopathology

• Colonoscopy • Moderate L sided ulcerative colitis • Rx: steroids + 5-ASA 2.4 g

Clinical remission

• 3 months later • Mayo Endoscopy Score = 0 • Robarts Histopathology Score (RHI) = 33 • Geboes Score = 5.3

Management?

Case 3: Histopathology