Inflammatory bowel disease

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Inflammatory bowel disease, abbreviated IBD, is the bread 'n butter of gastroenterology.

It exists in two main flavours:

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

Both are associated with an increased risk of colorectal carcinoma.[1]

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.[2]
  • People with long standing IBD have an increased risk for:

Extra-intestinal manifestations of inflammatory bowel disease

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

Molecular

  • NOD2[5] (AKA CARD15) variants are associated with stricturing CD, early need for surgery and recurrence.[6]

General clinical differential diagnosis

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

Others:

Microscopic

Features helpful for the diagnosis of IBD - as based on a study:[7]

  1. Basal inflammation, i.e. crypt base, plasmacytosis with severe chronic inflammation.
    • Basal cell plasmacytosis makes an infectious etiology less likely.[8]
    • "Basal plasmacytosis" = plasma cells in the lamina propria between the crypts and muscularis mucosae.[9]
  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[10] - 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.[11]

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.[12]
  4. Stretching of tissue may mimic atrophy; tip-off it is artefact: thinning of mucosa.[8]

Images:

Grading

  • Several systems exists.[8]
  • One that is often cited is by Gupta et al..[13]

Grading schemes for IBD in a table

Nil Mild Moderate Severe
"A grading scheme"[8] - cryptitis PMN abscesses erosions
Gupta[13] "0" (nil) "1" (<50% of crypts
have PMNs) 		"2" (>50% of crypts
have PMNs) 		"3" (presence of
ulcers or erosions)

Crohn's disease vs. ulcerative colitis

Robbins

UC features:[14]

  • 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 inflammed crypt, i.e. they may be present in UC.[15][16]
      • 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:

Kirsch

Features of UC[8] - memory device DDDR:

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

Words of caution

The following may be present in UC:[8]

  • 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:[17]

  • 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.

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 ? yes

Ulcerative colitis

  • Often abbreviated as UC.

General

  • May be associated with toxic megacolon.

Epidemiology:

Gross

  • Conventionally considered to be contiguous, i.e. no "skip lesions", with rectal involvement being most severe.
  • Dependent on the study one reads... rectal sparing may be seen in 15% of UC patients.[20]

Microscopic

Features:

  • Lack of granulomas.
  • No full wall-thickness inflammation.

Crohn's disease

General

  • Often abbreviated as CD.
  • Increased risk for cancer - usu. rectal cancer; classically mucinous adenocarcinoma.

Gross

  • Aphthous ulcer - first gross finding of IBD.
  • Transmural inflammation, i.e. full thickness of bowel wall.
  • Creeping fat (also "fat wrapping" and "fat hypertrophy"[21]) - abundant fat, fat on anti-mesenteric side of the bowel.[22]
  • Cobblestone appearance -- may be described as such on endoscopy; due to edema.
  • Serpiginous ulcers.

Microscopic

Features:[7]

  • Segmental crypt architectural abnormalities.
  • Mucin depletion -- less goblet cells. (???)[24]
  • Mucin preservation at the active sites.
  • Focal chronic inflammation without crypt atrophy.

DDx:

"Indeterminate colitis"

  • "Indeterminate colitis" is a confusing term and should be avoided.[25]

Terminology

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

Dysplasia-associated lesion or mass

  • Abbreviated DALM.

General

  • Proving invasive malignancy (on histopathologic grounds alone) in the setting of chronic inflammation is difficult.[26]
  • This diagnosis depends on correlation of endoscopy and histopathology - important.[27]
    • Biopsies are usually taken of the lesion and around the base.

Microscopic

Features:

DDx:

  • Sporadic adenomatous polyp -- favouring sporadic:
    • Sharp transition between lesion and the surrounding tissue.[27]
    • Polyps not at site of active disease.[28]

Image:

Pouchitis

General

  • Inflammation of an ileal pouch - a treatment for ulcerative colitis.
  • Chronic pouchitis seen in approximately 15% of patients.[29]
  • May be assessed by fecal calprotectin.[30]
  • Considered a clinico-pathologic diagnosis.[31][29]

Microscopic

Features:[32]

  • Neutrophils.
  • +/-Crypt abscess - indicator of moderate or severe.
  • Ulceration.

Scoring system

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

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

The histologic component of the PDAI:[32]

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

See also

References

  1. ↑ Schmidt C, Bielecki C, Felber J, Stallmach A (June 2010). "Surveillance strategies in inflammatory bowel disease". Minerva Gastroenterol Dietol 56 (2): 189–201. PMID 20485256.
  2. ↑ URL: http://www.gihealthfoundation.org/library/ppts/postcolectomypatient.pdf. 3 March 2011.
  3. ↑ 3.0 3.1 Claessen, MM.; Siersema, PD.; Vleggaar, FP. (Apr 2011). "IBD-related carcinoma.". Best Pract Res Clin Gastroenterol 25 Suppl 1: S27-38. doi:10.1016/S1521-6918(11)70007-5. PMID 21640928.
  4. ↑ Vos, AC.; Bakkal, N.; Minnee, RC.; Casparie, MK.; de Jong, DJ.; Dijkstra, G.; Stokkers, P.; van Bodegraven, AA. et al. (Sep 2011). "Risk of malignant lymphoma in patients with inflammatory bowel diseases: A Dutch nationwide study.". Inflamm Bowel Dis 17 (9): 1837-1845. doi:10.1002/ibd.21582. PMID 21830262.
  5. ↑ Online 'Mendelian Inheritance in Man' (OMIM) 605956
  6. ↑ Alvarez-Lobos M, Arostegui JI, Sans M, et al. (November 2005). "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". Ann. Surg. 242 (5): 693–700. PMC 1409853. PMID 16244543. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1409853/.
  7. ↑ 7.0 7.1 Tanaka M, Riddell RH, Saito H, Soma Y, Hidaka H, Kudo H (January 1999). "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". Scand. J. Gastroenterol. 34 (1): 55–67. PMID 10048734.
  8. ↑ 8.0 8.1 8.2 8.3 8.4 8.5 Kirsch, R. 13 December 2010.
  9. ↑ "Pathology of ulcerative colitis". http://www.histopathology-india.net/UlCol.htm. Retrieved 17 January 2011.
  10. ↑ Tanaka M, Saito H, Kusumi T, et al (December 2001). "Spatial distribution and histogenesis of colorectal Paneth cell metaplasia in idiopathic inflammatory bowel disease". J. Gastroenterol. Hepatol. 16 (12): 1353–9. PMID 11851832. http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0815-9319&date=2001&volume=16&issue=12&spage=1353.
  11. ↑ Rubio CA, Nesi G (2003). "A simple method to demonstrate normal and metaplastic Paneth cells in tissue sections". In Vivo 17 (1): 67–71. PMID 12655793.
  12. ↑ STC. 14 December 2009.
  13. ↑ 13.0 13.1 Gupta RB, Harpaz N, Itzkowitz S, et al. (October 2007). "Histologic inflammation is a risk factor for progression to colorectal neoplasia in ulcerative colitis: a cohort study". Gastroenterology 133 (4): 1099–105; quiz 1340–1. doi:10.1053/j.gastro.2007.08.001. PMC 2175077. PMID 17919486. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2175077/.
  14. ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 850. ISBN 0-7216-0187-1.
  15. ↑ Shepherd, NA. (Aug 2002). "Granulomas in the diagnosis of intestinal Crohn's disease: a myth exploded?". Histopathology 41 (2): 166-8. PMID 12147095.
  16. ↑ Mahadeva, U.; Martin, JP.; Patel, NK.; Price, AB. (Jul 2002). "Granulomatous ulcerative colitis: a re-appraisal of the mucosal granuloma in the distinction of Crohn's disease from ulcerative colitis.". Histopathology 41 (1): 50-5. PMID 12121237.
  17. ↑ Lin J, McKenna BJ, Appelman HD (November 2010). "Morphologic findings in upper gastrointestinal biopsies of patients with ulcerative colitis: a controlled study". Am. J. Surg. Pathol. 34 (11): 1672–7. doi:10.1097/PAS.0b013e3181f3de93. PMID 20962621.
  18. ↑ Beaugerie, L.; Sokol, H. (Aug 2009). "Appendicitis, not appendectomy, is protective against ulcerative colitis, both in the general population and first-degree relatives of patients with IBD.". Inflamm Bowel Dis. doi:10.1002/ibd.21064. PMID 19685454.
  19. ↑ 19.0 19.1 Timmer, A.; Obermeier, F. (2009). "Reduced risk of ulcerative colitis after appendicectomy.". BMJ 338: b225. PMID 19273505.
  20. ↑ Bernstein CN, Shanahan F, Anton PA, Weinstein WM (September 1995). "Patchiness of mucosal inflammation in treated ulcerative colitis: a prospective study". Gastrointest. Endosc. 42 (3): 232-7. PMID 7498688.
  21. ↑ Schäffler, A.; Herfarth, H. (Jun 2005). "Creeping fat in Crohn's disease: travelling in a creeper lane of research?". Gut 54 (6): 742-4. doi:10.1136/gut.2004.061531. PMID 15888774.
  22. ↑ Schäffler, A.; Herfarth, H. (Jun 2005). "Creeping fat in Crohn's disease: travelling in a creeper lane of research?". Gut 54 (6): 742-4. doi:10.1136/gut.2004.061531. PMID 15888774.
  23. ↑ Golder, WA. (Jan 2009). "The "creeping fat sign"-really diagnostic for Crohn's disease?". Int J Colorectal Dis 24 (1): 1-4. doi:10.1007/s00384-008-0585-y. PMID 18815796.
  24. ↑ McCormick DA, Horton LW, Mee AS (February 1990). "Mucin depletion in inflammatory bowel disease". J. Clin. Pathol. 43 (2): 143–6. PMC 502296. PMID 2318990. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC502296/.
  25. ↑ Geboes K, Colombel JF, Greenstein A, et al. (June 2008). "Indeterminate colitis: a review of the concept--what's in a name?". Inflamm. Bowel Dis. 14 (6): 850–7. doi:10.1002/ibd.20361. PMID 18213696.
  26. ↑ 26.0 26.1 Blackstone, MO.; Riddell, RH.; Rogers, BH.; Levin, B. (Feb 1981). "Dysplasia-associated lesion or mass (DALM) detected by colonoscopy in long-standing ulcerative colitis: an indication for colectomy.". Gastroenterology 80 (2): 366-74. PMID 7450425.
  27. ↑ 27.0 27.1 27.2 Neumann, H.; Vieth, M.; Langner, C.; Neurath, MF.; Mudter, J. (Jul 2011). "Cancer risk in IBD: how to diagnose and how to manage DALM and ALM.". World J Gastroenterol 17 (27): 3184-91. doi:10.3748/wjg.v17.i27.3184. PMID 21912466.
  28. ↑ Fogt, F.; Urbanski, SJ.; Sanders, ME.; Furth, EE.; Zimmerman, RL.; Deren, JJ.; Noffsinger, AE.; Vortmeyer, AO. et al. (Mar 2000). "Distinction between dysplasia-associated lesion or mass (DALM) and adenoma in patients with ulcerative colitis.". Hum Pathol 31 (3): 288-91. PMID 10746669.
  29. ↑ 29.0 29.1 Gionchetti, P.; Amadini, C.; Rizzello, F.; Venturi, A.; Poggioli, G.; Campieri, M. (Feb 2003). "Diagnosis and treatment of pouchitis.". Best Pract Res Clin Gastroenterol 17 (1): 75-87. PMID 12617884.
  30. ↑ Johnson, MW.; Maestranzi, S.; Duffy, AM.; Dewar, DH.; Forbes, A.; Bjarnason, I.; Sherwood, RA.; Ciclitira, P. et al. (Mar 2008). "Faecal calprotectin: a noninvasive diagnostic tool and marker of severity in pouchitis.". Eur J Gastroenterol Hepatol 20 (3): 174-9. doi:10.1097/MEG.0b013e3282f1c9a7. PMID 18301296.
  31. ↑ Royston, DJ.; Warren, BF. (Nov 2011). "Are we reporting ileal pouch biopsies correctly?". Colorectal Dis 13 (11): 1285-9. doi:10.1111/j.1463-1318.2010.02452.x. PMID 20958905.
  32. ↑ 32.0 32.1 Shen, B.; Achkar, JP.; Connor, JT.; Ormsby, AH.; Remzi, FH.; Bevins, CL.; Brzezinski, A.; Bambrick, ML. et al. (Jun 2003). "Modified pouchitis disease activity index: a simplified approach to the diagnosis of pouchitis.". Dis Colon Rectum 46 (6): 748-53. doi:10.1097/01.DCR.0000070528.00563.D9. PMID 12794576.

External links

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