Inflammatory bowel disease

Inflammatory bowel disease, abbreviated IBD, is the bread 'n butter of gastroenterology, and a significant number of gastrointestinal pathology specimens.

It exists in two main flavours:

• Crohn's disease (CD).
• Ulcerative colitis (UC).

Both are associated with an increased risk of colorectal carcinoma.

Clinical

• It is important to differentiate UC and CD as the management is different.
• UC patients get pouches... CD patients do not.
  • It is said that: There 's nothing like a pouch to bring out Crohn's disease.
• People with long standing IBD have an increased risk for:
  • Carcinoma - usually colorectal carcinoma.
    • Small increased risk for small bowel adenocarcinoma in Crohn's disease.
  • Lymphoma - in association with thiopurine use.

Extra-intestinal manifestations of inflammatory bowel disease

Mnemonic (family-rated version) excellent cardiac surgery is pleasant and appreciated:

• Erythema nodosum.
• Clubbing.
• Sclerosing cholangitis.
• Iritis.
• Pyoderma gangrenosum.
• Aphthous ulcers.
• Arthritis.

Molecular

• NOD2 (AKA CARD15) variants are associated with stricturing CD, early need for surgery and recurrence.

General clinical differential diagnosis

• Crohn's disease.
• Ulcerative colitis.
• Infective colitis/enteritis.
• Ischemic colitis/enteritis.
• Radiation colitis.

Others:

• Irritable bowel syndrome.

Specimens

• Biopsies for diagnosis.
• Surveillance biopsies - to rule-out dysplasia.
• Resections for disease that has failed medical management.
• Resections for dysplasia associated with inflammatory bowel disease.

Notes:

• Biopsies for diagnosis should specify the (anatomical) site:
  • Slight gradients exist in the large bowel that can be exploited for diagnostic purposes if the site information is known, for example:
    • Paneth cells distal to the splenic flexure are abnormal.
    • Ulcerative colitis is often more severe distally - even in a pancolitis, as the disease starts in the rectum and progresses toward the cecum.
• Surveillance biopsies should specify the (anatomical) site - so, it possible to find any site of interest on a follow-up colonoscopy.

Biopsies all submitted in one bottle

COLON (SITE NOT FURTHER SPECIFIED), BIOPSIES:
- MODERATE CHRONIC ACTIVE COLITIS.
- NEGATIVE FOR DYSPLASIA.
- PLEASE SEE COMMENT.

COMMENT:
The sections show colorectal-type mucosa with focal cryptitis and rare neutrophilic crypt
abscesses.  

Mild architectural changes, suggestive of a chronic colitis, are present. No granulomas are
identified. Lymphoid aggregates with germinal centre formation are present in multiple
fragments.  The lamina propria has abundant plasma cells throughout the fragments; no 
fragments have apparent relative sparing. 

Paneth cells are present focally; however, the significance of the paneth cells cannot 
determined as the biopsy sites are not known. 

The findings are compatible with inflammatory bowel disease and chronic active infectious
colitides. Clinical correlation is suggested.

Microscopic

Features helpful for the diagnosis of IBD - as based on a study:

1. Basal inflammation, i.e. crypt base, plasmacytosis with severe chronic inflammation.
   • Basal cell plasmacytosis makes an infectious etiology less likely.
   • "Basal plasmacytosis" = plasma cells in the lamina propria between the crypts and muscularis mucosae.
2. Crypt architectural abnormalities.
   • Atrophy = less glands ~ 3-4 glands/mm (normal = 7-8 glands/mm).
   • Branching = common (normal = very rare branching).
   • Distortion = bent glands, marked size variation (normal = "rack of test tubes").
3. Distal Paneth cell metaplasia.
   • Paneth cells should not be in the left colon - if you see 'em think of IBD and other long-standing injurious processes.
   • Paneth cells have basal nuclei and coarse luminal granules.
     • They should not be confused with endocrine cells -- these have apical nuclei and fine granules.
     • They should not be confused with intraepithelial eosinophils -- have smaller (~1/2) more intensely red granules.

Notes:

1. Microscopic features can be remembered by mnemonic CPP: Crypts (abnormal), Plasmacytosis, Paneth cells where they don't belong.
2. If you see architectural distortion (e.g. crypt branching) in the left colon, look for Paneth cells.
3. The hepatic flexure is considered the divider for normal paneth cells and abnormal paneth cells, i.e. paneth cells proximal to the hepatic flexure are normal; paneth cells distal to the hepatic flexure are abnormal.
4. Stretching of tissue may mimic atrophy; tip-off it is artifact: thinning of mucosa.

Images

• 

  Crohn's disease - very well-formed granulomas in the colon - high mag. (WC)

• 

  Crohn's disease - duodenum - intermed. mag. (WC)

• 

  Cryptitis. (WC)

• 

  Crypt branching. (WC)

Grading

• Several systems exists.
• One that is often cited is by Gupta et al.

Grading schemes for IBD in a table

	Nil	Mild	Moderate	Severe
"A grading scheme"	-	cryptitis	crypt abscesses	erosions
Gupta	"0" (nil)	"1" (<50% of crypts have PMNs)	"2" (>50% of crypts have PMNs)	"3" (presence of ulcers or erosions)

Images

• 

  Cryptitis. (WC)

• 

  Crypt abscess. (WC)

Crohn's disease versus ulcerative colitis

• Some cases cannot be classified by the experts (see "indeterminate colitis").

Robbins

UC features:

• Mucosal involvement -- sometimes submucosa.
• No skip lesions.
• Colon/rectum only.
  • UC may have 'ileal backwash' -- mild ileal inflammation due to backwash of inflammatory soup from colon.
• "No granulomas".
  • Superficial granulomas in the mucosa are non-specific, especially if they are beside an inflamed crypt, i.e. they may be present in UC.
    • Deep granulomas are specific for Crohn's disease.

Example of a superficial granuloma that is non-specific, i.e. this could be UC or CD:

• Colitis with a superficial granuloma (WC).

Kirsch

Features of UC - memory device DDDR:

• Diffuse inflammation.
• Diffuse arch. changes.
• Diffuse atrophy.
• Rectal involvement.

Words of caution

The following may be present in UC:

• Cecal patch (cecal involvement without pancolitis).
• Patchy involvement
  • Esp. in Tx'ed patients.
  • Esp. in children.
• Ileitis - esp. in the context of severe pancolitis; known as backwash ileitis.
• Deep inflammation (in a fissure).
• Upper GI tract involvement -- see below.

Upper gastrointestinal tract involvement

• The old dogma was upper GI tract = Crohn's disease.

Characteristics of upper GI tract UC:

• Most common:
  1. Focal gastritis.
  2. Mixed basal inflammation and superficial plasmacytosis in the stomach.
• Unique:
  • Diffuse chronic duodenitis.
  • ~ 10% of UC patients.
  • ~ 40% of UC + colectomy + pouchitis.

Another study compares UC, CD and control individuals:

• Gastritis:
  • UC: 19%.
  • CD: 33%
  • Controls: 13%.
• Duodenitis:
  • UC: 3%.
  • CD: 26%.
  • Controls: 1%.

Note:

• Younger individuals (<18 years old) have significantly more gastritis and duodenitis.

A tabular comparison

Gross pathology:

Feature	Crohn's disease	Ulcerative colitis
Lesion distribution	patchy	diffuse
Strictures	maybe	no
Perianal disease	yes/no	no
Rectal involvement	no	yes
Ileal involvement	yes, classic	usu. no; seen in pancolitis
Upper GI tract involvement	yes	yes (gaining acceptance)
Associated with PSC	not classically	yes

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Quiescent inflammatory bowel disease

• No accepted formal definition.

May be used when:

1. Non-specific "minimal abnormalities" are present.
2. There is a history of inflammatory bowel disease.

"Minimal abnormalities" - features:

• Apoptosis.
• Macrophages in the lamina propria.
• Lymphoid nodules.
• "Abundant" plasma cells in the lamina propria.
  • Abundant is subjective.

COLON, BIOPSIES:
- QUIESCENT INFLAMMATORY BOWEL DISEASE.
- NEGATIVE FOR DYSPLASIA.

Mild inflammation

SIGMOID COLON, BIOPSY:
- MILD ACTIVE COLITIS WITH CHRONIC CHANGES, SEE COMMENT.
- NEGATIVE FOR DYSPLASIA.

COMMENT:
No granulomata are identified.  Mild architectural changes are present.

The findings are compatible with inflammatory bowel disease or an infectious
etiology. Clinical correlation is required.

Mild-to-moderate inflammation

COLON, LEFT, BIOPSY:
- MILD-TO-MODERATE ACTIVE COLITIS WITH CHRONIC CHANGES.
- NEGATIVE FOR DYSPLASIA.

COMMENT:
No definite granulomata are identified.  Mild architectural changes are present.
Cryptitis is seen in several crypts. Rare crypt abscesses are present. Lamina propria
plasma cells are abundant throughout the biopsy.

The findings are compatible with inflammatory bowel disease or an infectious
etiology. Clinical correlation is required.

Moderate inflammation

RECTUM, BIOPSY:
- RECTAL MUCOSA WITH MODERATE ACTIVE INFLAMMATION AND CHRONIC CHANGES.
- NEGATIVE FOR DYSPLASIA.
- SEE COMMENT.

COMMENT:
No definite granulomata are identified. Architectural changes, including crypt drop out,
are present. Lamina propria plasma cells are abundant throughout the biopsy and eosinophil 
numbers are mildly increased. Lymphoid aggregates with germinal centre formation are 
present. All fragments of tissue are affected.

The findings are compatible with inflammatory bowel disease or an infectious
etiology. Clinical correlation is required.

Specific diagnoses

Ulcerative colitis

• Often abbreviated as UC.

Main article: Ulcerative colitis

Crohn's disease

• Abbreviated CD.

Main article: Crohn's disease

"Indeterminate colitis"

• "Indeterminate colitis" is a confusing term and should be avoided.

Suggested terminology

1. IBDU = IBD unclassified.
2. CUTE = Colitis of uncertain type or etiology.
   • Should be reserved for resection specimens only.

Dysplasia in inflammatory bowel disease

General

Classified as per Riddell et al.:

• Negative for dysplasia.
• Indefinite for dysplasia.
• Low grade dysplasia.
• High grade dysplasia.

Notes:

• GI experts and generalists have similar rates of agreement.

Microscopic

Features:

• Nuclear changes at the surface - key feature.
  • Nuclear hyperchromasia.
  • Nuclear enlargement - ellipsoid or spherical.

Dysplasia-associated lesion or mass

• Abbreviated DALM.

Main article: Dysplasia-associated lesion or mass

Pouchitis

General

• Inflammation of an ileal pouch; pouches are a treatment for ulcerative colitis.
  • Generally, pouches are not used in Crohn's disease.
• Chronic pouchitis seen in approximately 15% of patients.
• May be assessed by fecal calprotectin.
• Considered a clinico-pathologic diagnosis.

Microscopic

Features:

• Neutrophils - intraepithelial (cryptitis).
• +/-Crypt abscess (cluster of neutrophils in a gland) - indicator of moderate or severe.
• Ulceration.

Note:

• Absence of Paneth cells and villi = colonic metaplasia, associated with inflammation.

DDx:

• Crohn's disease - pyloric gland metaplasia (PGM) suggestive but not diagnostic.
  • PGM = glands with tall columnar cells with pale pink cytoplasm and a small basal nuclei - typically in the deep mucosa.
• Irritable pouch disease - functional disease similar to irritable bowel syndrome.

Images:

• Pouchitis (nih.gov).
• Colonic metaplasia (nih.gov).

Scoring system

Pouchitis disease activity index (PDAI) - based on clinical and pathologic factors:

• Active pouchitis >= 7.
• Remission < 7.

The histologic component of the PDAI:

• Neutrophils.
  • Mild.
  • Moderate - crypt abscesses.
  • Severe - crypt abscesses.
• Ulceration per LPF (mean).
  • <25%.
  • 25-50%.
  • >50.

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Note:

• Dr. Robert Riddell is of the opinion: "Do not call any pouch inflammation as consistent with Crohn's disease."

SMALL BOWEL POUCH, BIOPSY:
- SMALL BOWEL MUCOSA WITH CHRONIC ACTIVE INFLAMMATION WITH ULCERATION, EARLY
  CRYPT ABSCESS FORMATION, CRYPTITIS, AND LOSS OF THE VILLOUS ARCHITECTURE.
- NEGATIVE FOR GRANULOMAS AND NEGATIVE FOR PYLORIC GLAND METAPLASIA.
- NEGATIVE FOR DYSPLASIA.

COMMENT:
The findings are consistent with pouchitis.

Pyloric gland metaplasia present

SMALL BOWEL POUCH, BIOPSY:
- SMALL BOWEL MUCOSA WITH CHRONIC ACTIVE INFLAMMATION WITH ULCERATION, EARLY
  CRYPT ABSCESS FORMATION, CRYPTITIS, AND LOSS OF THE VILLOUS ARCHITECTURE.
- PYLORIC GLAND METAPLASIA, FOCAL, SEE COMMENT.
- NEGATIVE FOR GRANULOMAS.
- NEGATIVE FOR DYSPLASIA.

COMMENT:
The presence of pyloric gland metaplasia raises the possibility of Crohn's disease;
however, in the context of previous biopsies with inflammation, the concurrent
negative ileal biopsy and lack of granulomas, this individual is favoured to have 
pouchitis.

See also

• Colon.
• Colorectal tumours.
• Common variable immunodeficiency.
• Gastrointestinal pathology.
• Intestinal polyps.
• Diverticular disease-associated colitis.
• Pseudopyloric mucous glands.

External links

• Crohn's disease vs. ulcerative colitis vs. pseudomembranous colitis puzzle (unibas.ch) in a collection of games by Katharina Glatz-Krieger.