Celiac sprue

Celiac sprue, also celiac disease, is a common pathology that affects the duodenum.

An introduction to gastrointestinal pathology is in the gastrointestinal pathology article. It covers basic gastrointestinal histology.

Etiology

Autoimmune.

Epidemiology

Associated with:

Dermatitis herpetiformis - skin condition.^[1]
- Tx: dapsone.
IgA deficiency - 10-15X more common in celiac disease vs. healthy controls.^[2]
Risk factor for gastrointestinal T cell lymphoma - known as: enteropathy-associated T cell lymphoma (EATL).
IgA nephropathy is associated with an increased frequency of celiac disease.^[3]
Esophageal squamous cell carcinoma - increased risk.^[4]

Variants of celiac sprue

Latent celiac sprue.
- ONLY intraepithelial lymphocytes.
- NO villous arch. change.
Refractory celiac sprue.
- Subclassified - see microscopic.
Collagenous sprue.
- Abundant mucosal collagen - see microscopic.

Clinical

Treatment

Gluten free diet.
- Mnemonic: BROW = barley, rye, oats, wheat.

Serologic testing

Anti-tissue transglutaminase (TTG) antibody -- >10 U/mL considered positive.^[5]
- Alternative test: anti-endomysial antibody.
Anti-gliadin antibodies.^[6]
IgA deficiency - associated with celiac sprue.

Microscopic

Features:^[7]

Intraepithelial lymphocytes (IELs) - key feature.
- Should be more pronounced at tips of villi.^[8]
- Criteria for number varies:
  - > 40 IELs / 100 enterocytes (epithelial cells).^[9]
  - > 25 IELs / 100 enterocytes (epithelial cells).^[10]
Loss of villi - important feature.
- Normal duodenal biopsy should have 3 good villi.
Plasma cells - abundant (weak feature).
Macrophages.
Mitosis increased (in the crypts).
+/-Collagen band (pink material in mucosa) - "Collagenous sprue"; must encompass ~25% of mucosa.

Image:

Celiac sprue (WC).

Notes:

If you see acute inflammatory cells, i.e. neutrophils, consider Giardiasis and other infectious etiologies.
Biopsy should consist of 2-3 sites. In children it is important to sample the duodenal cap, as it is the only affected site in ~10% of cases.
Flat lesions without IELs are unlikely to be celiac sprue.
Mucosa erosions are rare in celiac sprue; should prompt consideration of an alternate diagnosis (infection, medications, Crohn's disease).
Biagi et al.^[8] count twenty cells in five (villi) tips.

Refractory sprue

Type I: CD3 ~= CD8.
Type II: CD3 20% + less than CD8.

Grading

Many pathologists do not grade celiac sprue.

Marsh

The Marsh system, also Marsh-Oberhuber:^[9]

Marsh score	Descriptors	Villi	Intraepithelial lymphocytes (IELs)	Crypts
Normal (Marsh 0)	normal	normal villi	< 40 / 100 epithelial cells	normal crypts
Marsh 1	IELs increased	normal villi	> 40 / 100 epithelial cells	normal crypts
Marsh 2	hypertrophic crypts, IELs	normal villi	> 40 / 100 epithelial cells	hypertrophic crypts
Marsh 3a	partial villous atrophy / blunted villi (mild)	mild atrophy	> 40 / 100 epithelial cells	hypertrophic crypts
Marsh 3b	moderate-to-marked villous atrophy / blunted villi (moderate-to-marked)	marked atrophy	> 40 / 100 epithelial cells	hypertrophic crypts
Marsh 3c	total villous atrophy, flattened mucosa	absent; flat as a pancake	> 40 / 100 epithelial cells	hypertrophic crypts

Simplified Marsh/Corazza

A simplified Marsh system - based (only) on villous architecture:^[10]

Grade	Similar Marsh grade	Descriptors	Alternate descriptors
A	Marsh 1	well-formed villi, IELs > 25/100 enterocytes	normal villous architecture
B1	Marsh 3a	partial villous atrophy; villous-crypt ratio < 3:1	blunted villi
B2	Marsh 3c	total villous atrophy	flattened mucosa

Notes:

Villous atrophy can be assessed endoscopically.^[11]

DDx

Giardiasis.
- Have giarrdia organisms.
- Always consider Giardiasis and especially on exams.
Whipple's disease (very rare).
- Abundant macrophages should make one suspicious.
Autoimmune enteropathy.
- Super duper rare.

IHC

CD3 -- marks the IELs.^[8]

Sign out

DUODENUM, BIOPSY: 
	- SMALL BOWEL MUCOSA WITH BRUNNER'S GLANDS, A MODERATE FOCAL INCREASE OF INTRAEPITHELIAL
	LYMPHOCYTES (>50 LYMPHOCYTES/100 ENTEROCYTES), A PRESERVATION OF VILLOUS ARCHITECTURE 
	AND CRYPTS WITHIN NORMAL LIMITS, SEE COMMENT. 

COMMENT: 
The findings are consistent with celiac disease, Marsh classification 1.

References

↑ Greenwald, J.; Heng, M. (2007). Toronto Notes for Medical Students 2007 (2007 ed.). The Toronto Notes Inc. for Medical Students Inc.. pp. D22. ISBN 978-0968592878.
↑ Kumar, V.; Jarzabek-Chorzelska, M.; Sulej, J.; Karnewska, K.; Farrell, T.; Jablonska, S. (Nov 2002). "Celiac disease and immunoglobulin a deficiency: how effective are the serological methods of diagnosis?". Clin Diagn Lab Immunol 9 (6): 1295-300. PMID 12414763.
↑ Smerud, HK.; Fellström, B.; Hällgren, R.; Osagie, S.; Venge, P.; Kristjánsson, G. (Aug 2009). "Gluten sensitivity in patients with IgA nephropathy.". Nephrol Dial Transplant 24 (8): 2476-81. doi:10.1093/ndt/gfp133. PMID 19332868.
↑ Messmann, H. (Apr 2001). "Squamous cell cancer of the oesophagus.". Best Pract Res Clin Gastroenterol 15 (2): 249-65. doi:10.1053/bega.2000.0172. PMID 11355914.
↑ URL: http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/82587. Accessed on: 13 August 2012.
↑ Matthias, T.; Pfeiffer, S.; Selmi, C.; Eric Gershwin, M. (Apr 2010). "Diagnostic challenges in celiac disease and the role of the tissue transglutaminase-neo-epitope.". Clin Rev Allergy Immunol 38 (2-3): 298-301. doi:10.1007/s12016-009-8160-z. PMID 19629760.
↑ 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. 843. ISBN 0-7216-0187-1.
↑ ^8.0 ^8.1 ^8.2 Biagi F, Luinetti O, Campanella J, et al. (August 2004). "Intraepithelial lymphocytes in the villous tip: do they indicate potential coeliac disease?". J. Clin. Pathol. 57 (8): 835–9. doi:10.1136/jcp.2003.013607. PMC 1770380. PMID 15280404. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1770380/.
↑ ^9.0 ^9.1 Oberhuber G, Granditsch G, Vogelsang H (October 1999). "The histopathology of coeliac disease: time for a standardized report scheme for pathologists". Eur J Gastroenterol Hepatol 11 (10): 1185–94. PMID 10524652.
↑ ^10.0 ^10.1 Corazza GR, Villanacci V, Zambelli C, et al. (July 2007). "Comparison of the interobserver reproducibility with different histologic criteria used in celiac disease". Clin. Gastroenterol. Hepatol. 5 (7): 838–43. doi:10.1016/j.cgh.2007.03.019. PMID 17544877.
↑ Ciaccio EJ, Bhagat G, Tennyson CA, Lewis SK, Hernandez L, Green PH (September 2010). "Quantitative Assessment of Endoscopic Images for Degree of Villous Atrophy in Celiac Disease". Dig Dis Sci. doi:10.1007/s10620-010-1371-6. PMID 20844959.

External links

Review article(s)

Serra S, Jani PA (November 2006). "An approach to duodenal biopsies". J. Clin. Pathol. 59 (11): 1133–50. doi:10.1136/jcp.2005.031260. PMC 1860495. PMID 16679353. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1860495/?tool=pubmed.

[Ref_TN2007_D22-1] Greenwald, J.; Heng, M. (2007). Toronto Notes for Medical Students 2007 (2007 ed.). The Toronto Notes Inc. for Medical Students Inc.. pp. D22. ISBN 978-0968592878.

[pmid12414763-2] Kumar, V.; Jarzabek-Chorzelska, M.; Sulej, J.; Karnewska, K.; Farrell, T.; Jablonska, S. (Nov 2002). "Celiac disease and immunoglobulin a deficiency: how effective are the serological methods of diagnosis?". Clin Diagn Lab Immunol 9 (6): 1295-300. PMID 12414763.

[pmid19332868-3] Smerud, HK.; Fellström, B.; Hällgren, R.; Osagie, S.; Venge, P.; Kristjánsson, G. (Aug 2009). "Gluten sensitivity in patients with IgA nephropathy.". Nephrol Dial Transplant 24 (8): 2476-81. doi:10.1093/ndt/gfp133. PMID 19332868.

[pmid11355914-4] Messmann, H. (Apr 2001). "Squamous cell cancer of the oesophagus.". Best Pract Res Clin Gastroenterol 15 (2): 249-65. doi:10.1053/bega.2000.0172. PMID 11355914.

[5] URL: http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/82587. Accessed on: 13 August 2012.

[pmid19629760-6] Matthias, T.; Pfeiffer, S.; Selmi, C.; Eric Gershwin, M. (Apr 2010). "Diagnostic challenges in celiac disease and the role of the tissue transglutaminase-neo-epitope.". Clin Rev Allergy Immunol 38 (2-3): 298-301. doi:10.1007/s12016-009-8160-z. PMID 19629760.

[Ref_PBoD843-7] 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. 843. ISBN 0-7216-0187-1.

[pmid15280404-8] 8.0 ^8.1 ^8.2 Biagi F, Luinetti O, Campanella J, et al. (August 2004). "Intraepithelial lymphocytes in the villous tip: do they indicate potential coeliac disease?". J. Clin. Pathol. 57 (8): 835–9. doi:10.1136/jcp.2003.013607. PMC 1770380. PMID 15280404. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1770380/.

[pmid10524652-9] 9.0 ^9.1 Oberhuber G, Granditsch G, Vogelsang H (October 1999). "The histopathology of coeliac disease: time for a standardized report scheme for pathologists". Eur J Gastroenterol Hepatol 11 (10): 1185–94. PMID 10524652.

[pmid17544877-10] 10.0 ^10.1 Corazza GR, Villanacci V, Zambelli C, et al. (July 2007). "Comparison of the interobserver reproducibility with different histologic criteria used in celiac disease". Clin. Gastroenterol. Hepatol. 5 (7): 838–43. doi:10.1016/j.cgh.2007.03.019. PMID 17544877.

[pmid20844959-11] Ciaccio EJ, Bhagat G, Tennyson CA, Lewis SK, Hernandez L, Green PH (September 2010). "Quantitative Assessment of Endoscopic Images for Degree of Villous Atrophy in Celiac Disease". Dig Dis Sci. doi:10.1007/s10620-010-1371-6. PMID 20844959.

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