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Pathology Jürg Vosbeck

Patho Basic Chronic Inflammatory Bowel Diseases

General

• Group of chronic relapsing diseases with chronic bloody or watery diarrhea

• Usually ulcerative colitis (UC) or Crohn’s disease (CD)

• Some cases of «indeterminate colitis»

Ulcerative colitis

• IBD of the large intestine

• Almost always begins in rectum

• May stay limited to rectum (ulcerative proctitis) or may extend to the entire colon in continuous fashion

• Maximum activity usually in distal colon

Ulcerative colitis

• Clinical course characterized by periods of exacerbation and remission («UC flares»)

• Rarely continuous low grade activity or initial single attack

• Involvement of terminal Ileum may occur in patients with pancolitis («backwash ileitis»), 5 – 25 cm, 10% total colectomies

Ulcerative colitis

• Primarily inflammation of mucosa (DD Crohn’s), but may involve deep layers in severe disease

• Classically diffuse distribution, however: false segmental distribution possible esp. in treated patients

• Cecal or periappendiceal patch

Ulcerative colitis

• Aetiology unknown

• One or more genetic factors in association with external factors and altered host immunology (failure to downregulate normal immune reaction?)

• Interplay microbes <–> immune system

Ulcerative colitis

• Appendectomy may be protective of UC (mechanism?)

• Smoking seems to be preventive!

• Abnormality of colonic mucus?

Ulcerative colitis

• Peak in 3rd decade, range all ages

• M<F

• Anglo-Saxon origin (N Europe, N America), Jews

UC Macro

• Frail erythematous mucosa, hemorrhagic bowel content (F: rectocolite ulcérohémorrhagique, RCUH)

• Relative rectal sparing in treated patients

UC Macro

• Relatively little fibrosis, mostly of rectal submucosa

• Inflammatory polyps/mucosal tags and mucosal islands common

UC Histo

• Histology:

– Active, resolving, in remission

• Active:

– Neutrophils, cryptitis, crypt abscesses

– «basal plasmocytosis», sometimes very large numbers of Eos or Mast cells

UC Histo

– Granulomas possible! But:

– Mucin-granulomas, reaction to damaged crypts («cryptolytic granulomas»).

– Location important; genuine sarcoid-type basally oriented granulomas don’t occur in UC.

UC Histo

• Resolving:

– Changes in crypt architecture

– Submucosal fibrosis

– Duplication of muscularis mucosae

– May occur in different rates depending on site -> false impression of segmental disease

Ulcerative colitis

• Extraintestinal manifestations:

– Primary sclerosing cholangitis (5% of all UC patients; 70% of PSC patients have UC)

– Arthritis, ankylosing spondylitis, Erythema nodosum, Uveitis...

UC Treatment

• Drugs:

– 1st line:

• 5-ASA (aminosalicylic acid), Steroids

– Refractory disease:

• Azathioprine, 6-Mercaptopurine, Tacrolimus, MTX…

– Novel therapies:

• Probiotics (alter bacterial flora); «stool transplantation»

UC Treatment

• Surgery:

– Colectomy

• Urgent in fulminant colitis, toxic megacolon, intractable bleeding

• Elective in refractory disease

– Ileoanal pouch

– Potentially curative

UC Prognosis

• Chronic, usually unrelenting

• Colonic adenocarcinoma in 3-5% of patients

– Risk: total colitis +/- backwash ileitis, early onset disease, > 8 years duration (some suggest > 5 yrs), PSC, family history

• Extensive disease: 19 fold risk compared to no

• Left sided disease: 4 fold risk

IBD Dysplasia

• Adenomas just like in healthy colon

• DALM concept outdated (dysplasia associated lesion or mass ->

colectomy)

• Adenoma resected endoscopically + biopsies taken around the base

– Biopsies w/o dysplasia -> no further actions

– Biopsies with dysplasia -> EMR, ESD, colectomy

Crohn’s Disease

• 1932, «regional enteritis» (terminal Ileitis)

• Involves any part of the gut, mouth to anus

• Restricted to colon in 15-30% of patients

• Rectum macroscopically normal in 50% of cases

Crohn’s Disease

Crohn’s Disease

• Incidence continues to increase (UC has reached plateau in 1990s)

• Peak 3rd decade, wide range • Aetiology remains mystery

– Genetic – Immunological

• Deficiency of innate intestinal mucosal barrier? • No autoimmunity involved

– Environmental: • Smoking is strong risk factor (<-> UC) • Appendectomy < 20 yrs. is a risk factor (<-> UC) • Microbes (sustained alterations of gut flora through dietary habits,

increased use of antibiotics)

Crohn’s Disease Macro

• Segmental disease

• Ulceration, strictures, thickening of gut wall

• Small aphthous lesions to complete loss of mucosa in extensive disease

• Cobblestone appearance as result of intercommunicating fissures

• Transmural extension, expansion to neighboring organs (abscesses, fistulae)

Crohn’s Disease Macro

• Esophageal: rare (<1%)

• Gastric: typically antral

• Duodenal: usually concomitant distal ileal or colonic disease

• Oral: 20-50%! Vesicles, aphthous ulcers

Crohn’s Disease Macro

• Nonalimentary tract: 25%

– Arthritis, sacroileitis, ankylos. spondylitis

– Erythema nodosum, vasculitis

– Uveitis, conjunctivitis

– Rarely PSC

Crohn’s Disease Histo

• Biopsy:

– Discontinuity of inflammation

– Granulomas

– Architectural abnormalities

• Terminal ileoscopic biopsies:

– Focal active inflammation, sometimes granulomas

– DD: NSAIDs, Yersiniosis, Behçet, UC...

Crohn’s Disease

• Surgical specimen:

– Focal ulceration, transmural inflammation with lymphoid aggregates, granulomas

– Hyperplasia of nerve fibers (submucosal and myenteric plexus)

• DD «diverticular colitis»

Crohn’s Disease Treatment

• Drugs:

– Aminosalicylates (…-salazines)

– Cyclosporin, steroids

– Azathioprine, Mercaptopurine

– Metronidazol, Ciprofloxacin

• Surgery:

– >60% repeated OPs, risk of short bowel syndrome

Crohn’s Disease Prognosis

• Recurrences in 95%

• Less prone to pre-cancerous and malignant changes in colon thank UC

• Risk of carcinoma in small bowel 10-20x compared to normal

Indeterminate colitis

• Term widely used with variety of definitions

• Aetiology and type of colitis can’t be identified properly

• Confusion:

– «Uncertainty whether or not IBD»

– «Patients with IBD but unsure if UC or Crohn’s»

-> clinical diagnosis of indeterminate colitis doesn’t necessarily mean that the patient has an IBD!

Indeterminate colitis

• Strict definition (Montreal classification):

– Colectomy has been performed and pathologists are unable to make a definitive diagnosis of either UC or Crohn’s

• In practice, distinction only of major importance if ileal pouch is considered (Crohn’s -> no ileal pouch)

Indeterminate colitis

• Temporary «diagnosis»

• Most cases will behave like UC (80-90%) -> ileal pouch not contraindicated

• Never use term on biopsy (inflammatory bowel disease of undetermined aetiology, IBDU, instead)

Summary

• Chronic inflammatory disease of colon (and small bowel) with many overlapping clinical and histological features

• -> interdisciplinary approach to correct patient handling

– Context, context, context!

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Indeterminate colitis

• Colectomy:

– UC

– Crohn’s

– «severe fulminant colitis without features of ulcerative colitis or Crohn’s disease» = indeterminate colitis

Indeterminate colitis

• Overlapping histological features of UC and Crohn’s

• Relative rectal sparing in UC