Difference between revisions of "Eosinophilic esophagitis"

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| Width      =
| Width      =
| Caption    = Eosinophilic esophagitis. [[H&E stain]].
| Caption    = Eosinophilic esophagitis. [[H&E stain]].
| Micro      = mucosa with "abundant eosinophils" (see ''microscopic''), [[basal cell hyperplasia]] (three cells thick ''or'' >15% of epithelial thickness), papillae elongated (reach into the top 1/3 of the epithelial layer)
| Micro      = mucosa with abundant eosinophils (60 per mm*mm), [[basal cell hyperplasia]] (three cells thick ''or'' >15% of epithelial thickness), papillae elongated (reach into the top 1/3 of the epithelial layer)  
| Subtypes  =
| Subtypes  =
| LMDDx      = [[GERD]]
| LMDDx      = [[GERD]]
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| Assdx      = atopy, [[celiac disease]]
| Assdx      = atopy, [[celiac disease]]
| Syndromes  =
| Syndromes  =
| Clinicalhx = unresponsive to proton pump inhibitors (PPIs)
| Clinicalhx = may be unresponsive to proton pump inhibitors (PPIs)
| Signs      =
| Signs      =
| Symptoms  = like [[GERD]]
| Symptoms  = similar to [[GERD]]
| Prevalence = uncommon
| Prevalence = uncommon
| Bloodwork  =
| Bloodwork  =
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*Avoid exacerbating antigens.
*Avoid exacerbating antigens.
*Topical corticosteroids, e.g. fluticasone.
*Topical corticosteroids, e.g. fluticasone.
*Do not respond to proton pump inhibitors.
 
Note on treatment:
*The classic teaching was that EE does not respond to proton pump inhibitors; thinking on this has evolved.<ref name=pmid30009819/>


Biopsies:
Biopsies:
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==Gross/endoscopic==
==Gross/endoscopic==
*'''Trachealization'''; eosphagus looks like trachea.<ref name=pmid19636182>{{Cite journal  | last1 = Al-Hussaini | first1 = AA. | last2 = Semaan | first2 = T. | last3 = El Hag | first3 = IA. | title = Esophageal trachealization: a feature of eosinophilic esophagitis. | journal = Saudi J Gastroenterol | volume = 15 | issue = 3 | pages = 193-5 | month =  | year =  | doi = 10.4103/1319-3767.54747 | PMID = 19636182 }}
*'''Trachealization'''; esophagus looks like trachea.<ref name=pmid19636182>{{Cite journal  | last1 = Al-Hussaini | first1 = AA. | last2 = Semaan | first2 = T. | last3 = El Hag | first3 = IA. | title = Esophageal trachealization: a feature of eosinophilic esophagitis. | journal = Saudi J Gastroenterol | volume = 15 | issue = 3 | pages = 193-5 | month =  | year =  | doi = 10.4103/1319-3767.54747 | PMID = 19636182 }}
</ref>
</ref>
**[[AKA]] ''feline esophagus''.<ref>URL: [http://www.ajronline.org/cgi/reprint/164/4/900.pdf  http://www.ajronline.org/cgi/reprint/164/4/900.pdf]. Accessed on: 4 October 2010.</ref>  
**[[AKA]] ''feline esophagus''.<ref>URL: [http://www.ajronline.org/cgi/reprint/164/4/900.pdf  http://www.ajronline.org/cgi/reprint/164/4/900.pdf]. Accessed on: 4 October 2010.</ref>  
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==Microscopic==
==Microscopic==
Features:<ref name=Ref_GLP19>{{Ref GLP|19}}</ref>
Features:<ref name=Ref_GLP19>{{Ref GLP|19}}</ref>
*Mucosa with "abundant eosinophils".
*Mucosa with abundant eosinophils - the consensus on eosinophils per area is 60/mm*mm.<ref name=pmid30009819>{{cite journal |authors=Dellon ES, Liacouras CA, Molina-Infante J, Furuta GT, Spergel JM, Zevit N, Spechler SJ, Attwood SE, Straumann A, Aceves SS, Alexander JA, Atkins D, Arva NC, Blanchard C, Bonis PA, Book WM, Capocelli KE, Chehade M, Cheng E, Collins MH, Davis CM, Dias JA, Di Lorenzo C, Dohil R, Dupont C, Falk GW, Ferreira CT, Fox A, Gonsalves NP, Gupta SK, Katzka DA, Kinoshita Y, Menard-Katcher C, Kodroff E, Metz DC, Miehlke S, Muir AB, Mukkada VA, Murch S, Nurko S, Ohtsuka Y, Orel R, Papadopoulou A, Peterson KA, Philpott H, Putnam PE, Richter JE, Rosen R, Rothenberg ME, Schoepfer A, Scott MM, Shah N, Sheikh J, Souza RF, Strobel MJ, Talley NJ, Vaezi MF, Vandenplas Y, Vieira MC, Walker MM, Wechsler JB, Wershil BK, Wen T, Yang GY, Hirano I, Bredenoord AJ |title=Updated International Consensus Diagnostic Criteria for Eosinophilic Esophagitis: Proceedings of the AGREE Conference |journal=Gastroenterology |volume=155 |issue=4 |pages=1022–1033.e10 |date=October 2018 |pmid=30009819 |pmc=6174113 |doi=10.1053/j.gastro.2018.07.009 |url=}}</ref>
*[[Basal cell hyperplasia]].
*[[Basal cell hyperplasia]].
**Three cells thick ''or'' >15% of epithelial thickness.
**Three cells thick ''or'' >15% of epithelial thickness.
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**Papillae that reach into the top 1/3 of the epithelial layer - definition for GERD.<ref name=Ref_PBoD804>{{Ref PBoD|804}}</ref>
**Papillae that reach into the top 1/3 of the epithelial layer - definition for GERD.<ref name=Ref_PBoD804>{{Ref PBoD|804}}</ref>


Notes "abundant eosinophils":
Note:
*Criteria for number of eosinophils/area is '''''highly variable'''''; there is a 23X fold variation in published values and only 11% of studies actually define an area (most studies, only give the number of eosinophils per "HPF")!<ref name=pmid17617209>{{cite journal |author=Dellon ES, Aderoju A, Woosley JT, Sandler RS, Shaheen NJ |title=Variability in diagnostic criteria for eosinophilic esophagitis: a systematic review |journal=Am. J. Gastroenterol. |volume=102 |issue=10 |pages=2300–13 |year=2007 |month=October |pmid=17617209 |doi=10.1111/j.1572-0241.2007.01396.x |url=}}</ref>
*Many microscopes have an eye piece diameter of 22 mm. Thus, the field area (for a "HPF") with the 40x objective is ~0.2376 mm*mm. This works out to approximately 15 eosinophils/HPF.
**Interrater variability is low, i.e. good, if the procedure is standardized.<ref name=pmid19830560>{{Cite journal  | last1 = Dellon | first1 = ES. | last2 = Fritchie | first2 = KJ. | last3 = Rubinas | first3 = TC. | last4 = Woosley | first4 = JT. | last5 = Shaheen | first5 = NJ. | title = Inter- and intraobserver reliability and validation of a new method for determination of eosinophil counts in patients with esophageal eosinophilia. | journal = Dig Dis Sci | volume = 55 | issue = 7 | pages = 1940-9 | month = Jul | year = 2010 | doi = 10.1007/s10620-009-1005-z | PMID = 19830560 }}</ref>
*The most commonly reported cut points are 15, 20 and 24 eosinophils/HPF, without defining HPF.<ref name=pmid17617209/>
**The ''Foundation Series'' book<ref name=Ref_GLP19>{{Ref GLP|19}}</ref> says: "> 20/HPF"; this is problematic as "HPF" is not defined (see [[HPFitis]]).
**There is a consensus paper<ref name=pmid17919504>{{cite journal |author=Furuta GT, Liacouras CA, Collins MH, ''et al.'' |title=Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment |journal=Gastroenterology |volume=133 |issue=4 |pages=1342–63 |year=2007 |month=October |pmid=17919504 |doi=10.1053/j.gastro.2007.08.017 |url=}}</ref> that makes note of [[HPFitis]]... and then goes on to ignore to whole issue by defining EE as 15/HPF! 
**Many microscopes have 22 mm eye pieces and have for their highest magnification objective a 40X.  De facto, these people are using the Liacouras ''et al.'' definition.<ref name=pmid16361045>{{cite journal |author=Liacouras CA, Spergel JM, Ruchelli E, ''et al.'' |title=Eosinophilic esophagitis: a 10-year experience in 381 children |journal=Clin. Gastroenterol. Hepatol. |volume=3 |issue=12 |pages=1198–206 |year=2005 |month=December |pmid=16361045 |doi= |url=}}</ref>
*Eosinophils may be patchy.<ref name=pmid22502795>{{Cite journal  | last1 = Saffari | first1 = H. | last2 = Peterson | first2 = KA. | last3 = Fang | first3 = JC. | last4 = Teman | first4 = C. | last5 = Gleich | first5 = GJ. | last6 = Pease | first6 = LF. | title = Patchy eosinophil distributions in an esophagectomy specimen from a patient with eosinophilic esophagitis: Implications for endoscopic biopsy. | journal = J Allergy Clin Immunol | volume = 130 | issue = 3 | pages = 798-800 | month = Sep | year = 2012 | doi = 10.1016/j.jaci.2012.03.009 | PMID = 22502795 }}</ref>


DDx:<ref name=Ref_Odze244>{{Ref Odze|244}}</ref>
DDx:<ref name=Ref_Odze244>{{Ref Odze|244}}</ref>
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===Images===  
===Images===  
<gallery>
<gallery>
Image:Eosinophilic_esophagitis_-_2_-_very_high_mag.jpg | Eosinophilic esophagitis - very high mag. (WC)
Image:Eosinophilic esophagitis - intermed mag.jpg | Intermed. mag. (WC)
Image:Eosinophilic_esophagitis_-_2_-_high_mag.jpg | Eosinophilic esophagitis - high mag. (WC)
Image:Eosinophilic esophagitis - high mag.jpg | High mag. (WC)
Image:Eosinophilic esophagitis - very high mag.jpg | Very high mag. (WC)
Image:Eosinophilic esophagitis - 2 - high mag.jpg | High mag. (WC)
Image:Eosinophilic esophagitis - 2 - very high mag.jpg | Very high mag. (WC)
</gallery>
</gallery>
====www====
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2841420/figure/F0003/ Eosinophilic esophagitis (nih.gov)].
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2841420/figure/F0003/ Eosinophilic esophagitis (nih.gov)].
*[http://www.archivesofpathology.org/action/showFullPopup?id=i1543-2165-134-6-815-f03&doi=10.1043%2F1543-2165-134.6.815 EE versus GERD (archivesofpathology.org)].<ref name=pmid20524860/>
*[http://www.archivesofpathology.org/action/showFullPopup?id=i1543-2165-134-6-815-f03&doi=10.1043%2F1543-2165-134.6.815 EE versus GERD (archivesofpathology.org)].<ref name=pmid20524860/>
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==Sign out==
==Sign out==
<pre>
A. Distal Esophagus, Biopsy:
      - Squamous mucosa with basal cell hyperplasia, abundant intraepithelial
        eosinophils, edema, and papillary elongation, see comment.
      - NEGATIVE for columnar type epithelium.
      - NEGATIVE for dysplasia.
B. Mid Esophagus, Biopsy:
      - Squamous mucosa with basal cell hyperplasia, abundant intraepithelial
        eosinophils, edema, and papillary elongation, see comment.
      - NEGATIVE for dysplasia.
COMMENT:
There are approximately 35 eosinophils per 0.2376 mm*mm (1 HPF) in
both Part A and Part B.
The above findings are suggestive of eosinophilic esophagitis in the proper
clinical context.
</pre>
===Block letters===
<pre>
<pre>
ESOPHAGUS, DISTAL, BIOPSY:
ESOPHAGUS, DISTAL, BIOPSY:
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COMMENT:
COMMENT:
There are approximately 65 eosinophils per 0.2376 mm*mm (1 HPF).  
There are approximately 65 eosinophils per 0.2376 mm*mm (1 HPF).  
Literature valves show a large variation when defining eosinophilic esophagitis
and frequently use "HPF" as a measure of area, which is not a standardized measure.
[Am. J. Gastroenterol. 102 (10): 2300–13.]
Common cut-points are 15 eosinophils/HPF and 20 eosinophils/HPF, where HPF is
often undefined.


The above findings are suggestive of eosinophilic esophagitis in the proper
The above findings are suggestive of eosinophilic esophagitis in the proper
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compatible with gastroesophageal reflux; however, eosinophilic esophagitis is also a
compatible with gastroesophageal reflux; however, eosinophilic esophagitis is also a
consideration. Clinical correlation is required.
consideration. Clinical correlation is required.
Literature valves show a large variation when defining eosinophilic esophagitis
and frequently use "HPF" as a measure of area, which is not a standardized measure.
[Am. J. Gastroenterol. 102 (10): 2300 13.]
Common cut-points are 15 eosinophils/HPF and 20 eosinophils/HPF, where HPF is
often undefined.
</pre>
</pre>


Latest revision as of 22:59, 27 January 2022

Eosinophilic esophagitis
Diagnosis in short

Eosinophilic esophagitis. H&E stain.
LM mucosa with abundant eosinophils (60 per mm*mm), basal cell hyperplasia (three cells thick or >15% of epithelial thickness), papillae elongated (reach into the top 1/3 of the epithelial layer)
LM DDx GERD
Site esophagus
Associated Dx atopy, celiac disease
Clinical history may be unresponsive to proton pump inhibitors (PPIs)
Symptoms similar to GERD
Prevalence uncommon
Endoscopy trachealization of esophagus (AKA feline esophagus)
Clin. DDx GERD

Eosinophilic esophagitis, abbreviated EE, is relatively uncommon pathology of the esophagus with some similarities to gastroesophageal reflux disease (GERD).

General

  • The current thinking is that it is a clinico-pathologic diagnosis.[1]

Clinical:

Treatment:

  • Avoid exacerbating antigens.
  • Topical corticosteroids, e.g. fluticasone.

Note on treatment:

  • The classic teaching was that EE does not respond to proton pump inhibitors; thinking on this has evolved.[4]

Biopsies:

  • Should be taken from: upper, mid, lower and submitted in separate containers (eosinophilia present through-out-- to differentiate from GERD).

Associations:

Gross/endoscopic

  • Trachealization; esophagus looks like trachea.[8]
  • White.

DDx (endoscopic):

Image

  • Trachealization of the esophagus. (WC)

Microscopic

Features:[5]

  • Mucosa with abundant eosinophils - the consensus on eosinophils per area is 60/mm*mm.[4]
  • Basal cell hyperplasia.
    • Three cells thick or >15% of epithelial thickness.
  • Papillae elongated.
    • Papillae that reach into the top 1/3 of the epithelial layer - definition for GERD.[10]

Note:

  • Many microscopes have an eye piece diameter of 22 mm. Thus, the field area (for a "HPF") with the 40x objective is ~0.2376 mm*mm. This works out to approximately 15 eosinophils/HPF.

DDx:[11]

Images

  • Intermed. mag. (WC)

  • High mag. (WC)

  • Very high mag. (WC)

  • High mag. (WC)

  • Very high mag. (WC)

www

Sign out

A. Distal Esophagus, Biopsy:
       - Squamous mucosa with basal cell hyperplasia, abundant intraepithelial
         eosinophils, edema, and papillary elongation, see comment.
       - NEGATIVE for columnar type epithelium.
       - NEGATIVE for dysplasia.

B. Mid Esophagus, Biopsy:
       - Squamous mucosa with basal cell hyperplasia, abundant intraepithelial
         eosinophils, edema, and papillary elongation, see comment.
       - NEGATIVE for dysplasia.

COMMENT:
There are approximately 35 eosinophils per 0.2376 mm*mm (1 HPF) in
both Part A and Part B.

The above findings are suggestive of eosinophilic esophagitis in the proper
clinical context.

Block letters

ESOPHAGUS, DISTAL, BIOPSY:
- SQUAMOUS MUCOSA WITH BASAL CELL HYPERPLASIA, ABUNDANT INTRAEPITHELIAL EOSINOPHILS, 
  EDEMA, AND PAPILLARY ELONGATION, SEE COMMENT.
- STAINS (PAS-D, GMS) NEGATIVE FOR MICROORGANISMS.
- NEGATIVE FOR INTESTINAL METAPLASIA.
- NEGATIVE FOR DYSPLASIA.

COMMENT:
There are approximately 65 eosinophils per 0.2376 mm*mm (1 HPF). 

The above findings are suggestive of eosinophilic esophagitis in the proper
clinical context.

Patchy eosinophils

ESOPHAGUS (DISTAL), BIOPSY:
- SQUAMOUS MUCOSA WITH BASAL CELL HYPERPLASIA, INTRAEPITHELIAL EDEMA AND ONLY
  FOCALLY ABUNDANT INTRAEPITHELIAL EOSINOPHILS, SEE COMMENT.
- COLUMNAR EPITHELIUM WITH MODERATE CHRONIC INFLAMMATION, AND PANCREATIC
  ACINAR METAPLASIA.
- NEGATIVE FOR INTESTINAL METAPLASIA.
- NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.

COMMENT:
One high power field (field diameter 0.55 mm) has 25 eosinophils. The findings are
compatible with gastroesophageal reflux; however, eosinophilic esophagitis is also a
consideration. Clinical correlation is required.

Histology suggestive

ESOPHAGUS, BIOPSY:
- SQUAMOUS MUCOSA WITH MARKED BASAL CELL HYPERPLASIA, FOCALLY ABUNDANT
  INTRAEPITHELIAL EOSINOPHILS, EDEMA, AND PAPILLARY ELONGATION, SEE COMMENT.
- NEGATIVE FOR INTESTINAL METAPLASIA.
- NEGATIVE FOR DYSPLASIA.

COMMENT:
Focally, there are approximately 35 eosinophils per 0.2376 mm*mm (1 HPF).

The above findings raise the possibility of eosinophilic esophagitis; clinical
correlation is suggested. A re-biopsy including a portion of the proximal esophagus
could be considered.

See also

References

  1. ↑ 1.0 1.1 Genevay, M.; Rubbia-Brandt, L.; Rougemont, AL. (Jun 2010). "Do eosinophil numbers differentiate eosinophilic esophagitis from gastroesophageal reflux disease?". Arch Pathol Lab Med 134 (6): 815-25. doi:10.1043/1543-2165-134.6.815. PMID 20524860. http://www.archivesofpathology.org/doi/full/10.1043/1543-2165-134.6.815.
  2. ↑ URL: http://www.medicinenet.com/eosinophilic_esophagitis/page2.htm#tocc. Accessed on: 1 December 2009.
  3. ↑ 3.0 3.1 3.2 Rothenberg, ME. (Oct 2009). "Biology and treatment of eosinophilic esophagitis.". Gastroenterology 137 (4): 1238-49. doi:10.1053/j.gastro.2009.07.007. PMID 19596009.
  4. ↑ 4.0 4.1 Dellon ES, Liacouras CA, Molina-Infante J, Furuta GT, Spergel JM, Zevit N, Spechler SJ, Attwood SE, Straumann A, Aceves SS, Alexander JA, Atkins D, Arva NC, Blanchard C, Bonis PA, Book WM, Capocelli KE, Chehade M, Cheng E, Collins MH, Davis CM, Dias JA, Di Lorenzo C, Dohil R, Dupont C, Falk GW, Ferreira CT, Fox A, Gonsalves NP, Gupta SK, Katzka DA, Kinoshita Y, Menard-Katcher C, Kodroff E, Metz DC, Miehlke S, Muir AB, Mukkada VA, Murch S, Nurko S, Ohtsuka Y, Orel R, Papadopoulou A, Peterson KA, Philpott H, Putnam PE, Richter JE, Rosen R, Rothenberg ME, Schoepfer A, Scott MM, Shah N, Sheikh J, Souza RF, Strobel MJ, Talley NJ, Vaezi MF, Vandenplas Y, Vieira MC, Walker MM, Wechsler JB, Wershil BK, Wen T, Yang GY, Hirano I, Bredenoord AJ (October 2018). "Updated International Consensus Diagnostic Criteria for Eosinophilic Esophagitis: Proceedings of the AGREE Conference". Gastroenterology 155 (4): 1022–1033.e10. doi:10.1053/j.gastro.2018.07.009. PMC 6174113. PMID 30009819. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6174113/.
  5. ↑ 5.0 5.1 Iacobuzio-Donahue, Christine A.; Montgomery, Elizabeth A. (2005). Gastrointestinal and Liver Pathology: A Volume in the Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 19. ISBN 978-0443066573.
  6. ↑ Leslie C, Mews C, Charles A, Ravikumara M (April 2010). "Celiac disease and eosinophilic esophagitis: a true association". J. Pediatr. Gastroenterol. Nutr. 50 (4): 397–9. doi:10.1097/MPG.0b013e3181a70af4. PMID 19841598.
  7. ↑ 7.0 7.1 Dellon, ES.; Erichsen, R.; Pedersen, L.; Shaheen, NJ.; Baron, JA.; Sørensen, HT.; Vyberg, M. (Jan 2013). "Development and validation of a registry-based definition of eosinophilic esophagitis in Denmark.". World J Gastroenterol 19 (4): 503-10. doi:10.3748/wjg.v19.i4.503. PMID 23382628.
  8. ↑ Al-Hussaini, AA.; Semaan, T.; El Hag, IA.. "Esophageal trachealization: a feature of eosinophilic esophagitis.". Saudi J Gastroenterol 15 (3): 193-5. doi:10.4103/1319-3767.54747. PMID 19636182.
  9. ↑ URL: http://www.ajronline.org/cgi/reprint/164/4/900.pdf. Accessed on: 4 October 2010.
  10. ↑ 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. 804. ISBN 0-7216-0187-1.
  11. ↑ Odze, Robert D.; Goldblum, John R. (2009). Surgical pathology of the GI tract, liver, biliary tract and pancreas (2nd ed.). Saunders. pp. 244. ISBN 978-1416040590.
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