Difference between revisions of "Inflammatory bowel disease"

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'''Inflammatory bowel disease''', abbreviated IBD, is the bread 'n butter of gastroenterology.   
'''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:
It exists in two main flavours:
Line 7: Line 7:
Both are associated with an increased risk of [[colorectal carcinoma]].<ref name=pmid20485256>{{cite journal |author=Schmidt C, Bielecki C, Felber J, Stallmach A |title=Surveillance strategies in inflammatory bowel disease |journal=Minerva Gastroenterol Dietol |volume=56 |issue=2 |pages=189–201 |year=2010 |month=June |pmid=20485256 |doi= |url=}}</ref>
Both are associated with an increased risk of [[colorectal carcinoma]].<ref name=pmid20485256>{{cite journal |author=Schmidt C, Bielecki C, Felber J, Stallmach A |title=Surveillance strategies in inflammatory bowel disease |journal=Minerva Gastroenterol Dietol |volume=56 |issue=2 |pages=189–201 |year=2010 |month=June |pmid=20485256 |doi= |url=}}</ref>


==Clinical==
=Clinical=
*It is important to differentiate UC and CD as the management is different.  
*It is important to differentiate UC and CD as the management is different.  
*UC patients get pouches... CD patients do not.
*UC patients get pouches... CD patients do not.
**It is said that: ''There 's nothing like a pouch to bring out Crohn's disease''.<ref>URL: [http://www.gihealthfoundation.org/library/ppts/postcolectomypatient.pdf http://www.gihealthfoundation.org/library/ppts/postcolectomypatient.pdf]. 3 March 2011.</ref>
*People with long standing IBD have an increased risk for:
**Carcinoma - usually [[colorectal carcinoma]].<ref name=pmid21640928>{{Cite journal  | last1 = Claessen | first1 = MM. | last2 = Siersema | first2 = PD. | last3 = Vleggaar | first3 = FP. | title = IBD-related carcinoma. | journal = Best Pract Res Clin Gastroenterol | volume = 25 Suppl 1 | issue =  | pages = S27-38 | month = Apr | year = 2011 | doi = 10.1016/S1521-6918(11)70007-5 | PMID = 21640928 }}</ref>
***Small increased risk for [[small bowel]] adenocarcinoma in Crohn's disease.<ref name=pmid21640928/>
**Lymphoma - in association with thiopurine use.<ref name=pmid21830262>{{Cite journal  | last1 = Vos | first1 = AC. | last2 = Bakkal | first2 = N. | last3 = Minnee | first3 = RC. | last4 = Casparie | first4 = MK. | last5 = de Jong | first5 = DJ. | last6 = Dijkstra | first6 = G. | last7 = Stokkers | first7 = P. | last8 = van Bodegraven | first8 = AA. | last9 = Pierik | first9 = M. | title = Risk of malignant lymphoma in patients with inflammatory bowel diseases: A Dutch nationwide study. | journal = Inflamm Bowel Dis | volume = 17 | issue = 9 | pages = 1837-1845 | month = Sep | year = 2011 | doi = 10.1002/ibd.21582 | PMID = 21830262 }}</ref>


==Epidemiology==
===Extra-intestinal manifestations of inflammatory bowel disease===
*NOD2/CARD15 variants are assoc. with stricturing CD, early need for surgery and recurrence.<ref name=pmid16244543 >{{cite journal |author=Alvarez-Lobos M, Arostegui JI, Sans M, ''et al.'' |title=Crohn's disease patients carrying Nod2/CARD15 gene variants have an increased and early need for first surgery due to stricturing disease and higher rate of surgical recurrence |journal=Ann. Surg. |volume=242 |issue=5 |pages=693–700 |year=2005 |month=November |pmid=16244543 |pmc=1409853 |doi= |url=}}</ref>
Mnemonic (family-rated version) '''''e'''xcellent '''c'''ardiac '''s'''urgery '''i'''s '''p'''leasant '''a'''nd '''a'''ppreciated'':
*[[erythema nodosum|'''E'''rythema nodosum]].
*[[Clubbing|'''C'''lubbing]].
*[[primary sclerosing cholangitis|'''S'''clerosing cholangitis]].
*[[Iritis|'''I'''ritis]].
*[[Pyoderma gangrenosum|'''P'''yoderma gangrenosum]].
*'''A'''phthous ulcers.
*[[Arthritis|'''A'''rthritis]].


==Microscopic==
===Molecular===
*NOD2<ref name=omim605956>{{OMIM|605956}}</ref> ([[AKA]] CARD15) variants are associated with stricturing CD, early need for surgery and recurrence.<ref name=pmid16244543 >{{cite journal |author=Alvarez-Lobos M, Arostegui JI, Sans M, ''et al.'' |title=Crohn's disease patients carrying Nod2/CARD15 gene variants have an increased and early need for first surgery due to stricturing disease and higher rate of surgical recurrence |journal=Ann. Surg. |volume=242 |issue=5 |pages=693–700 |year=2005 |month=November |pmid=16244543 |pmc=1409853 |doi= |url=}}</ref>
 
===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 cell]]s 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.<ref name=pmid16609751>{{Cite journal  | last1 = Panaccione | first1 = R. | title = The approach to dysplasia surveillance in inflammatory bowel disease. | journal = Can J Gastroenterol | volume = 20 | issue = 4 | pages = 251-3 | month = Apr | year = 2006 | doi =  | PMID = 16609751 | PMC = 2659899}}</ref>
 
===Biopsies all submitted in one bottle===
<pre>
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.
</pre>
 
=Microscopic=
Features helpful for the diagnosis of IBD - as based on a study:<ref name=pmid10048734>{{cite journal |author=Tanaka M, Riddell RH, Saito H, Soma Y, Hidaka H, Kudo H |title=Morphologic criteria applicable to biopsy specimens for effective distinction of inflammatory bowel disease from other forms of colitis and of Crohn's disease from ulcerative colitis |journal=Scand. J. Gastroenterol. |volume=34 |issue=1 |pages=55–67 |year=1999 |month=January |pmid=10048734 |doi= |url=}}</ref>
Features helpful for the diagnosis of IBD - as based on a study:<ref name=pmid10048734>{{cite journal |author=Tanaka M, Riddell RH, Saito H, Soma Y, Hidaka H, Kudo H |title=Morphologic criteria applicable to biopsy specimens for effective distinction of inflammatory bowel disease from other forms of colitis and of Crohn's disease from ulcerative colitis |journal=Scand. J. Gastroenterol. |volume=34 |issue=1 |pages=55–67 |year=1999 |month=January |pmid=10048734 |doi= |url=}}</ref>
#Basal inflammation, i.e. crypt base, plasmacytosis with severe chronic inflammation.
#Basal inflammation, i.e. crypt base, plasmacytosis with severe chronic inflammation.
#*Basal cell plasmacytosis makes an infectious etiology less likely.<ref name=Kirsch>Kirsch, R. 13 December 2010.</ref>
#*"Basal plasmacytosis" = plasma cells in the lamina propria between the crypts and muscularis mucosae.<ref>{{cite web |url=http://www.histopathology-india.net/UlCol.htm |title=Pathology of ulcerative colitis |author= |date= |work= |publisher= |accessdate=17 January 2011}}</ref>
#Crypt architectural abnormalities.
#Crypt architectural abnormalities.
#*Atrophy = less glands ~ 3-4 glands/mm (normal = 7-8 glands/mm).
#*Atrophy = less glands ~ 3-4 glands/mm (normal = 7-8 glands/mm).
#*Branching = common (normal = very rare branching).
#*Branching = common (normal = very rare branching).
#*Distortion = bent glands, marked size variation (normal = "rack of test tubes").
#*Distortion = bent glands, marked size variation<ref>URL: [http://www.histopath.com.au/assets/documents/Inflammatory%20bowel%20disease.pdf http://www.histopath.com.au/assets/documents/Inflammatory%20bowel%20disease.pdf]. Accessed on: 25 October 2013.</ref> (normal = "rack of test tubes").
#Distal Paneth cell metaplasia.
#Distal Paneth cell metaplasia.
#*Paneth cells should ''not'' be in the left colon<ref name=pmid11851832>{{cite journal |author=Tanaka M, Saito H, Kusumi T, ''et al'' |title=Spatial distribution and histogenesis of colorectal Paneth cell metaplasia in idiopathic inflammatory bowel disease |journal=J. Gastroenterol. Hepatol. |volume=16 |issue=12 |pages=1353–9 |year=2001 |month=December |pmid=11851832 |doi= |url=http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0815-9319&date=2001&volume=16&issue=12&spage=1353}}</ref> - if you see 'em think of IBD and other long-standing injurious processes.
#*Paneth cells should ''not'' be in the left colon<ref name=pmid11851832>{{cite journal |author=Tanaka M, Saito H, Kusumi T, ''et al'' |title=Spatial distribution and histogenesis of colorectal Paneth cell metaplasia in idiopathic inflammatory bowel disease |journal=J. Gastroenterol. Hepatol. |volume=16 |issue=12 |pages=1353–9 |year=2001 |month=December |pmid=11851832 |doi= |url=http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0815-9319&date=2001&volume=16&issue=12&spage=1353}}</ref> - if you see 'em think of IBD and other long-standing injurious processes.
#*Some claim that (friendly right colonic) paneth cells and paneth cell metaplasia look quite different and can be distinguished.<ref name=pmid12655793>{{cite journal |author=Rubio CA, Nesi G |title=A simple method to demonstrate normal and metaplastic Paneth cells in tissue sections |journal=In Vivo |volume=17 |issue=1 |pages=67–71 |year=2003 |pmid=12655793 |doi= |url=}}</ref>
#*Paneth cells have basal nuclei and coarse luminal granules.<ref name=Ref_H4P3_631>{{Ref H4P3|631}}</ref>
 
#**They should '''not''' be confused with endocrine cells -- these have apical nuclei and fine granules.
#**They should '''not''' be confused with intraepithelial [[eosinophil]]s -- have smaller (~1/2) more intensely red granules.
Notes:  
Notes:  
# Microscopic features can be remembered by [[mnemonic]] ''CPP'': Crypts (abnormal), Plasmacytosis, Paneth cells where they don't belong.
# Microscopic features can be remembered by [[mnemonic]] ''CPP'': Crypts (abnormal), Plasmacytosis, Paneth cells where they don't belong.
# If you see architectural distortion (e.g. crypt branching) in the left colon, look for Paneth cells.
# If you see architectural distortion (e.g. crypt branching) in the left colon, look for Paneth cells.
# 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.<ref>STC. 14 December 2009.</ref>
# 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.<ref>STC. 14 December 2009.</ref>
# Stretching of tissue may mimic atrophy; tip-off it is artefact: thinning of mucosa.<ref>RK. 13 December 2010.</ref>
# Stretching of tissue may mimic atrophy; tip-off it is artifact: thinning of mucosa.<ref name=Kirsch>Kirsch, R. 13 December 2010.</ref>
 
====Images====
<gallery>
Image:Crohn%27s_disease_-_colon_-_high_mag.jpg | Crohn's disease - very well-formed granulomas in the [[colon]] - high mag. (WC)
Image:Crohn%27s_disease_-_duodenum_-_intermed_mag.jpg | Crohn's disease - duodenum - intermed. mag. (WC)
Image: Cryptitis_-_alt_--_very_high_mag.jpg | Cryptitis. (WC)
Image:Crypt_branching_high_mag.jpg | Crypt branching. (WC)
</gallery>


===Grading===
===Grading===
*Several systems exists.<ref>RK. 13 December 2010.</ref>
*Several systems exists.<ref name=Kirsch>Kirsch, R. 13 December 2010.</ref>
*One that is often cited is by Gupta et al..<ref name=pmid17919486>{{cite journal |author=Gupta RB, Harpaz N, Itzkowitz S, ''et al.'' |title=Histologic inflammation is a risk factor for progression to colorectal neoplasia in ulcerative colitis: a cohort study |journal=Gastroenterology |volume=133 |issue=4 |pages=1099–105; quiz 1340–1 |year=2007 |month=October |pmid=17919486 |pmc=2175077 |doi=10.1053/j.gastro.2007.08.001 |url=}}</ref>
*One that is often cited is by Gupta et al.<ref name=pmid17919486>{{cite journal |author=Gupta RB, Harpaz N, Itzkowitz S, ''et al.'' |title=Histologic inflammation is a risk factor for progression to colorectal neoplasia in ulcerative colitis: a cohort study |journal=Gastroenterology |volume=133 |issue=4 |pages=1099–105; quiz 1340–1 |year=2007 |month=October |pmid=17919486 |pmc=2175077 |doi=10.1053/j.gastro.2007.08.001 |url=}}</ref>


====Grading schemes for IBD in a table====
====Grading schemes for IBD in a table====
Line 43: Line 115:
| '''Severe'''
| '''Severe'''
|-
|-
| "A grading scheme"<ref>RK. 13 December 2010.</ref>
| "A grading scheme"<ref name=Kirsch>Kirsch, R. 13 December 2010.</ref>
| -
| -
| cryptitis
| [[cryptitis]]
| PMN abscesses
| [[crypt abscesses]]
| erosions
| erosions
|-
|-
Line 56: Line 128:
|-
|-
|}
|}
=====Images=====
<gallery>
Image: Cryptitis_--_very_high_mag.jpg | [[Cryptitis]]. (WC)
Image: Crypt_abscess_--_very_high_mag.jpg | [[Crypt abscess]]. (WC)
</gallery>
==Crohn's disease versus ulcerative colitis==
*Some cases cannot be classified by the experts (see [[Inflammatory_bowel_disease#.22Indeterminate_colitis.22|"indeterminate colitis"]]).


==Crohn's disease vs. ulcerative colitis==
===Robbins===
UC features:<ref name=Ref_PBoD850>{{Ref PBoD|850}}</ref>
UC features:<ref name=Ref_PBoD850>{{Ref PBoD|850}}</ref>
*Mucosal involvement --sometimes submucosa.  
*Mucosal involvement -- sometimes submucosa.  
*No skip lesions.  
*No skip lesions.  
*Colon/rectum only.  
*Colon/rectum only.  
** UC may have 'ileal backwash' -- mild ileal inflammation due to backwash of inflammatory soup from colon.
** UC may have 'ileal backwash' -- mild ileal inflammation due to backwash of inflammatory soup from colon.
*"No granulomas".
*"No granulomas".
**Superficial granulomas in the mucosa are non-specific, especially if they are beside an inflammed crypt, i.e. they may be present in UC.<ref name=pmid12147095>{{Cite journal  | last1 = Shepherd | first1 = NA. | title = Granulomas in the diagnosis of intestinal Crohn's disease: a myth exploded? | journal = Histopathology | volume = 41 | issue = 2 | pages = 166-8 | month = Aug | year = 2002 | doi =  | PMID = 12147095 }}</ref><ref name=pmid12121237>{{Cite journal  | last1 = Mahadeva | first1 = U. | last2 = Martin | first2 = JP. | last3 = Patel | first3 = NK. | last4 = Price | first4 = AB. | title = Granulomatous ulcerative colitis: a re-appraisal of the mucosal granuloma in the distinction of Crohn's disease from ulcerative colitis. | journal = Histopathology | volume = 41 | issue = 1 | pages = 50-5 | month = Jul | year = 2002 | doi =  | PMID = 12121237 }}</ref>
**Superficial [[granulomas]] in the mucosa are non-specific, especially if they are beside an inflamed crypt, i.e. they may be present in UC.<ref name=pmid12147095>{{Cite journal  | last1 = Shepherd | first1 = NA. | title = Granulomas in the diagnosis of intestinal Crohn's disease: a myth exploded? | journal = Histopathology | volume = 41 | issue = 2 | pages = 166-8 | month = Aug | year = 2002 | doi =  | PMID = 12147095 }}</ref><ref name=pmid12121237>{{Cite journal  | last1 = Mahadeva | first1 = U. | last2 = Martin | first2 = JP. | last3 = Patel | first3 = NK. | last4 = Price | first4 = AB. | title = Granulomatous ulcerative colitis: a re-appraisal of the mucosal granuloma in the distinction of Crohn's disease from ulcerative colitis. | journal = Histopathology | volume = 41 | issue = 1 | pages = 50-5 | month = Jul | year = 2002 | doi =  | PMID = 12121237 }}</ref>
***Deep granulomas are specific for Crohn's disease.
***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:
Example of a superficial granuloma that is non-specific, i.e. this could be UC or CD:
*[http://commons.wikimedia.org/wiki/File:Colitis_with_granuloma_low_mag.jpg Colitis with a superficial granuloma (wikimedia.org)].
*[http://commons.wikimedia.org/wiki/File:Colitis_with_granuloma_low_mag.jpg Colitis with a superficial granuloma (WC)].
 
===Kirsch===
Features of UC<ref name=Kirsch>Kirsch, R. 13 December 2010.</ref> - memory device ''DDDR'':
*Diffuse inflammation.
*Diffuse arch. changes.
*Diffuse atrophy.
*Rectal involvement.
 
====Words of caution====
The following may be present in UC:<ref name=Kirsch>Kirsch, R. 13 December 2010.</ref>
*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:<ref name=pmid20962621>{{cite journal |author=Lin J, McKenna BJ, Appelman HD |title=Morphologic findings in upper gastrointestinal biopsies of patients with ulcerative colitis: a controlled study |journal=Am. J. Surg. Pathol. |volume=34 |issue=11 |pages=1672–7 |year=2010 |month=November |pmid=20962621 |doi=10.1097/PAS.0b013e3181f3de93 |url=}}</ref>
*Most common:
*#Focal gastritis.
*#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:<ref name=pmid20848539>{{Cite journal  | last1 = Sonnenberg | first1 = A. | last2 = Melton | first2 = SD. | last3 = Genta | first3 = RM. | title = Frequent occurrence of gastritis and duodenitis in patients with inflammatory bowel disease. | journal = Inflamm Bowel Dis | volume = 17 | issue = 1 | pages = 39-44 | month = Jan | year = 2011 | doi = 10.1002/ibd.21356 | PMID = 20848539 }}</ref>
*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.<ref name=pmid20848539/>
 
====A tabular comparison====
Gross pathology:
{| class="wikitable"
| '''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
|-
|}
 
=Sign out=
===Quiescent inflammatory bowel disease===
*No accepted formal definition.
 
May be used when:
#Non-specific "minimal abnormalities" are present.
#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.
 
<pre>
COLON, BIOPSIES:
- QUIESCENT INFLAMMATORY BOWEL DISEASE.
- NEGATIVE FOR DYSPLASIA.
</pre>


===Mild inflammation===
<pre>
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.
</pre>
===Mild-to-moderate inflammation===
<pre>
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.
</pre>
===Moderate inflammation===
<pre>
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.
</pre>
=Specific diagnoses=
==Ulcerative colitis==
==Ulcerative colitis==
===General===
*Often abbreviated as ''UC''.
*Often abbreviated as ''UC''.
{{Main|Ulcerative colitis}}
==Crohn's disease==
*Abbreviated ''CD''.
{{Main|Crohn's disease}}
=="Indeterminate colitis"==
*"Indeterminate colitis" is a confusing term and should be avoided.<ref name=pmid18213696>{{cite journal |author=Geboes K, Colombel JF, Greenstein A, ''et al.'' |title=Indeterminate colitis: a review of the concept--what's in a name? |journal=Inflamm. Bowel Dis. |volume=14 |issue=6 |pages=850–7 |year=2008 |month=June |pmid=18213696 |doi=10.1002/ibd.20361 |url=}}</ref>
===Suggested terminology===
#IBDU = IBD unclassified.
#CUTE = Colitis of uncertain type or etiology.
#*Should be reserved for resection specimens only.


===Epidemiology===
==Dysplasia in inflammatory bowel disease==
*Associated with ''[[sclerosing cholangitis]]''.
===General===
*Appendicitis is considered protective against UC.<ref name=pmid19685454>{{Cite journal  | last1 = Beaugerie | first1 = L. | last2 = Sokol | first2 = H. | title = Appendicitis, not appendectomy, is protective against ulcerative colitis, both in the general population and first-degree relatives of patients with IBD. | journal = Inflamm Bowel Dis | volume = | issue = | pages = | month = Aug | year = 2009 | doi = 10.1002/ibd.21064 | PMID = 19685454 }}</ref><ref name=pmid19273505>{{Cite journal  | last1 = Timmer | first1 = A. | last2 = Obermeier | first2 = F. | title = Reduced risk of ulcerative colitis after appendicectomy. | journal = BMJ | volume = 338 | issue =  | pages = b225 | month = | year = 2009 | doi =  | PMID = 19273505 }}</ref>
Classified as per Riddell ''et al.'':<ref name=pmid6629368>{{Cite journal  | last1 = Riddell | first1 = RH. | last2 = Goldman | first2 = H. | last3 = Ransohoff | first3 = DF. | last4 = Appelman | first4 = HD. | last5 = Fenoglio | first5 = CM. | last6 = Haggitt | first6 = RC. | last7 = Ahren | first7 = C. | last8 = Correa | first8 = P. | last9 = Hamilton | first9 = SR. | title = Dysplasia in inflammatory bowel disease: standardized classification with provisional clinical applications. | journal = Hum Pathol | volume = 14 | issue = 11 | pages = 931-68 | month = Nov | year = 1983 | doi = | PMID = 6629368 }}</ref><ref name=pmid11400142>{{Cite journal  | last1 = Eaden | first1 = J. | last2 = Abrams | first2 = K. | last3 = McKay | first3 = H. | last4 = Denley | first4 = H. | last5 = Mayberry | first5 = J. | title = Inter-observer variation between general and specialist gastrointestinal pathologists when grading dysplasia in ulcerative colitis. | journal = J Pathol | volume = 194 | issue = 2 | pages = 152-7 | month = Jun | year = 2001 | doi = 10.1002/path.876 | PMID = 11400142 }}</ref><ref name=pmid11936264>{{Cite journal | last1 = Greenson | first1 = JK. | title = Dysplasia in inflammatory bowel disease. | journal = Semin Diagn Pathol | volume = 19 | issue = 1 | pages = 31-7 | month = Feb | year = 2002 | doi =  | PMID = 11936264 }}</ref>
*Smoking is protective; the opposite is true for Crohn's disease.<ref name=pmid19273505/>
*Negative for dysplasia.
*[[Indefinite for dysplasia]].
*Low grade dysplasia.
*High grade dysplasia.


===Gross===
Notes:
*Conventionally considered to be contiguous, i.e. no "skip lesions", with rectal involvement being most severe.
*GI experts and generalists have similar rates of agreement.<ref name=pmid11400142>{{Cite journal | last1 = Eaden | first1 = J. | last2 = Abrams | first2 = K. | last3 = McKay | first3 = H. | last4 = Denley | first4 = H. | last5 = Mayberry | first5 = J. | title = Inter-observer variation between general and specialist gastrointestinal pathologists when grading dysplasia in ulcerative colitis. | journal = J Pathol | volume = 194 | issue = 2 | pages = 152-7 | month = Jun | year = 2001 | doi = 10.1002/path.876 | PMID = 11400142 }}</ref>
*Dependent on the study one reads... rectal sparing may be seen in 15% of UC patients.<ref>{{cite journal |author=Bernstein CN, Shanahan F, Anton PA, Weinstein WM |title=Patchiness of mucosal inflammation in treated ulcerative colitis: a prospective study |journal=Gastrointest. Endosc. |volume=42 |issue=3 |pages=232-7 |year=1995 |month=September |pmid=7498688 |doi= |url=}}</ref>


===Microscopic===
===Microscopic===
*Lack of granulomas.
Features:<ref>URL: [http://surgpathcriteria.stanford.edu/gi/ulcerative-colitis/printable.html http://surgpathcriteria.stanford.edu/gi/ulcerative-colitis/printable.html]. Accessed on: 12 March 2013.</ref>
*No full wall-thickness inflammation.
*Nuclear changes at the surface - '''key feature'''.
**Nuclear hyperchromasia.
**Nuclear enlargement - ellipsoid ''or'' spherical.


==Crohn's disease==
==Dysplasia-associated lesion or mass==
*Abbreviated ''DALM''.
{{Main|Dysplasia-associated lesion or mass}}
 
==Pouchitis==
===General===
===General===
*Often abbreviated as ''CD''.
*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.<ref name=pmid12617884 >{{Cite journal  | last1 = Gionchetti | first1 = P. | last2 = Amadini | first2 = C. | last3 = Rizzello | first3 = F. | last4 = Venturi | first4 = A. | last5 = Poggioli | first5 = G. | last6 = Campieri | first6 = M. | title = Diagnosis and treatment of pouchitis. | journal = Best Pract Res Clin Gastroenterol | volume = 17 | issue = 1 | pages = 75-87 | month = Feb | year = 2003 | doi =  | PMID = 12617884 }}</ref>
*May be assessed by [[fecal calprotectin]].<ref name=pmid18301296>{{Cite journal  | last1 = Johnson | first1 = MW. | last2 = Maestranzi | first2 = S. | last3 = Duffy | first3 = AM. | last4 = Dewar | first4 = DH. | last5 = Forbes | first5 = A. | last6 = Bjarnason | first6 = I. | last7 = Sherwood | first7 = RA. | last8 = Ciclitira | first8 = P. | last9 = Nicholls | first9 = JR. | title = Faecal calprotectin: a noninvasive diagnostic tool and marker of severity in pouchitis. | journal = Eur J Gastroenterol Hepatol | volume = 20 | issue = 3 | pages = 174-9 | month = Mar | year = 2008 | doi = 10.1097/MEG.0b013e3282f1c9a7 | PMID = 18301296 }}</ref>
*Considered a clinico-pathologic diagnosis.<ref name=pmid20958905>{{Cite journal  | last1 = Royston | first1 = DJ. | last2 = Warren | first2 = BF. | title = Are we reporting ileal pouch biopsies correctly? | journal = Colorectal Dis | volume = 13 | issue = 11 | pages = 1285-9 | month = Nov | year = 2011 | doi = 10.1111/j.1463-1318.2010.02452.x | PMID = 20958905 }}</ref><ref name=pmid12617884 >{{Cite journal  | last1 = Gionchetti | first1 = P. | last2 = Amadini | first2 = C. | last3 = Rizzello | first3 = F. | last4 = Venturi | first4 = A. | last5 = Poggioli | first5 = G. | last6 = Campieri | first6 = M. | title = Diagnosis and treatment of pouchitis. | journal = Best Pract Res Clin Gastroenterol | volume = 17 | issue = 1 | pages = 75-87 | month = Feb | year = 2003 | doi =  | PMID = 12617884 }}</ref>
===Microscopic===
Features:<ref name=pmid12794576>{{Cite journal  | last1 = Shen | first1 = B. | last2 = Achkar | first2 = JP. | last3 = Connor | first3 = JT. | last4 = Ormsby | first4 = AH. | last5 = Remzi | first5 = FH. | last6 = Bevins | first6 = CL. | last7 = Brzezinski | first7 = A. | last8 = Bambrick | first8 = ML. | last9 = Fazio | first9 = VW. | title = Modified pouchitis disease activity index: a simplified approach to the diagnosis of pouchitis. | journal = Dis Colon Rectum | volume = 46 | issue = 6 | pages = 748-53 | month = Jun | year = 2003 | doi = 10.1097/01.DCR.0000070528.00563.D9 | PMID = 12794576 | URL = http://www.lri.ccf.org/pathobio/achkar/documents/Shen2003DisColonRectum.pdf }}</ref>
*[[Neutrophil]]s - 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,<ref name=pmid22892912/> associated with inflammation.<ref>{{Cite journal  | last1 = Fruin | first1 = AB. | last2 = El-Zammer | first2 = O. | last3 = Stucchi | first3 = AF. | last4 = O'Brien | first4 = M. | last5 = Becker | first5 = JM. | title = Colonic metaplasia in the ileal pouch is associated with inflammation and is not the result of long-term adaptation. | journal = J Gastrointest Surg | volume = 7 | issue = 2 | pages = 246-53; discussion 253-4 | month = Feb | year = 2003 | doi =  | PMID = 12600449 }}</ref>
 
DDx:
*[[Crohn's disease]] - [[pyloric gland metaplasia]] (PGM) suggestive but not diagnostic.<ref name=pmid23543088>{{Cite journal  | last1 = Agarwal | first1 = S. | last2 = Stucchi | first2 = AF. | last3 = Dendrinos | first3 = K. | last4 = Cerda | first4 = S. | last5 = O'Brien | first5 = MJ. | last6 = Becker | first6 = JM. | last7 = Heeren | first7 = T. | last8 = Farraye | first8 = FA. | title = Is pyloric gland metaplasia in ileal pouch biopsies a marker for Crohn's disease? | journal = Dig Dis Sci | volume = 58 | issue = 10 | pages = 2918-25 | month = Oct | year = 2013 | doi = 10.1007/s10620-013-2655-4 | PMID = 23543088 }}</ref>
**PGM = glands with tall columnar cells with pale pink cytoplasm and a small basal nuclei - typically in the deep mucosa.<ref name=pmid23925821>{{Cite journal  | last1 = Weber | first1 = CR. | last2 = Rubin | first2 = DT. | title = Chronic pouchitis versus recurrent Crohn's disease: a diagnostic challenge. | journal = Dig Dis Sci | volume = 58 | issue = 10 | pages = 2748-50 | month = Oct | year = 2013 | doi = 10.1007/s10620-013-2816-5 | PMID = 23925821 }}</ref>
*Irritable pouch disease<ref name=pmid15073663>{{Cite journal  | last1 = Beart | first1 = RW. | title = Is pouchitis a clinical, endoscopic, or histologic problem? | journal = Dis Colon Rectum | volume = 47 | issue = 6 | pages = 949; author reply 949-50 | month = Jun | year = 2004 | doi = 10.1007/s10350-004-0516-0 | PMID = 15073663 }}</ref><ref name=pmid18702649>{{Cite journal  | last1 = Shen | first1 = B. | last2 = Liu | first2 = W. | last3 = Remzi | first3 = FH. | last4 = Shao | first4 = Z. | last5 = Lu | first5 = H. | last6 = DeLaMotte | first6 = C. | last7 = Hammel | first7 = J. | last8 = Queener | first8 = E. | last9 = Bambrick | first9 = ML. | title = Enterochromaffin cell hyperplasia in irritable pouch syndrome. | journal = Am J Gastroenterol | volume = 103 | issue = 9 | pages = 2293-300 | month = Sep | year = 2008 | doi = 10.1111/j.1572-0241.2008.01990.x | PMID = 18702649 }}</ref> - functional disease similar to [[irritable bowel syndrome]].
 
Images:
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3400158/figure/f4-cln_67p705/ Pouchitis (nih.gov)].<ref name=pmid22892912>{{Cite journal  | last1 = Arashiro | first1 = RT. | last2 = Teixeira | first2 = MG. | last3 = Rawet | first3 = V. | last4 = Quintanilha | first4 = AG. | last5 = Paula | first5 = HM. | last6 = Silva | first6 = AZ. | last7 = Nahas | first7 = SC. | last8 = Cecconello | first8 = I. | title = Histopathological evaluation and risk factors related to the development of pouchitis in patients with ileal pouches for ulcerative colitis. | journal = Clinics (Sao Paulo) | volume = 67 | issue = 7 | pages = 705-10 | month = Jul | year = 2012 | doi =  | PMID = 22892912 | PMC = 3400158 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3400158/}}</ref>
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3400158/figure/f3-cln_67p705/ Colonic metaplasia (nih.gov)].<ref name=pmid22892912/>
 
====Scoring system====
Pouchitis disease activity index (PDAI) - based on clinical and pathologic factors:
*Active pouchitis >= 7.
*Remission < 7.
 
The histologic component of the PDAI:<ref name=pmid12794576/>
*Neutrophils.
**Mild.
**Moderate - crypt abscesses.
**Severe - crypt abscesses.
*Ulceration per [[LPF]] (mean).
**<25%.
**25-50%.
**>50.
 
===Sign out===
Note:
*Dr. Robert Riddell is of the opinion: "Do '''not''' call any pouch inflammation as consistent with Crohn's disease."
 
<pre>
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.
</pre>


===Gross===
====Pyloric gland metaplasia present====
*Transmural inflammation, i.e. full thickness of bowel wall.
<pre>
*Creeping fat.
SMALL BOWEL POUCH, BIOPSY:
*Cobblestone appearance -- may be described as such on endoscopy.
- SMALL BOWEL MUCOSA WITH CHRONIC ACTIVE INFLAMMATION WITH ULCERATION, EARLY
*Serpiginous ulcers.  
  CRYPT ABSCESS FORMATION, CRYPTITIS, AND LOSS OF THE VILLOUS ARCHITECTURE.
** Image: [http://en.wikipedia.org/wiki/File:CD_serpiginous_ulcer.jpg Serpiginous ulcer (endoscopy) - wikipedia.org].
- PYLORIC GLAND METAPLASIA, FOCAL, SEE COMMENT.
- NEGATIVE FOR GRANULOMAS.
- NEGATIVE FOR DYSPLASIA.


===Microscopic===
COMMENT:
Features:<ref name=pmid10048734/>
The presence of pyloric gland metaplasia raises the possibility of Crohn's disease;
*Segmental crypt architectural abnormalities,
however, in the context of previous biopsies with inflammation, the concurrent
*Mucin depletion,
negative ileal biopsy and lack of granulomas, this individual is favoured to have
*Mucin preservation at the active sites, and
pouchitis.</pre>
*Focal chronic inflammation without crypt atrophy.


==See also==
=See also=
*[[GIST]].
*[[Colon]].
*[[Colorectal tumours]].
*[[Common variable immunodeficiency]].
*[[Gastrointestinal pathology]].
*[[Gastrointestinal pathology]].
*[[Intestinal polyps]].
*[[Intestinal polyps]].
*[[Colon]].
*[[Diverticular disease-associated colitis]].
*[[Colorectal tumours]].
*[[Pseudopyloric mucous glands]].


==References==
=References=
{{reflist|2}}
{{reflist|2}}
=External links=
*[http://kathrin.unibas.ch/game/diffdiag01/index.html Crohn's disease vs. ulcerative colitis vs. pseudomembranous colitis puzzle (unibas.ch)] in a collection of [http://kathrin.unibas.ch/game/index.html games] by [http://kathrin.unibas.ch/kathrin/ Katharina Glatz-Krieger].


[[Category:Gastrointestinal pathology]]
[[Category:Gastrointestinal pathology]]
Michael
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