Eosinophilic esophagitis

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

Eosinophilic esophagitis
Diagnosis in short

Eosinophilic esophagitis. H&E stain.

LM 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)
LM DDx GERD
Site esophagus

Associated Dx atopy, celiac disease
Clinical history unresponsive to proton pump inhibitors (PPIs)
Symptoms like GERD
Prevalence uncommon
Endoscopy trachealization of esophagus (AKA feline esophagus)
Clin. DDx GERD

General

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

Clinical:

Treatment:

  • Avoid exacerbating antigens.
  • Topical corticosteroids, e.g. fluticasone.
  • Do not respond to proton pump inhibitors.

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; eosphagus looks like trachea.[7]
  • White.

DDx (endoscopic):

Image

Microscopic

Features:[4]

  • Mucosa with "abundant eosinophils".
  • 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.[9]

Notes "abundant eosinophils":

  • 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, embarassing for pathologists that understand this issue, only give the number of eosinophils per "HPF")![10]
    • Interrater variability is low, i.e. good, if the procedure is standardized.[11]
  • The most commonly reported cut points are 15, 20 and 24 eosinophils/HPF, without defining HPF.[10]
    • The Foundation Series book[4] says: "> 20/HPF"; onlinepathology sees this definition as garbage, as "HPF" is not defined (see HPFitis).
    • There is a consensus paper[12] that makes note of HPFitis... and then goes on to ignore to whole issue by defining EE as 15/HPF. It blows my mind that the people could be so will fully blind and that the idiotic reviewers didn't understand this.
    • Most resident microscopes at the Toronto teaching hospitals have 22 mm eye pieces and have for their highest magnification objective a 40X. De facto, this means most people in Toronto are using the Liacouras et al. definition.[13]
  • Eosinophils may be patchy.[14]

DDx:[15]

Images

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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). 

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
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.

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.

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 4.2 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.
  5. 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.
  6. 6.0 6.1 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.
  7. 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.
  8. URL: http://www.ajronline.org/cgi/reprint/164/4/900.pdf. Accessed on: 4 October 2010.
  9. 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.
  10. 10.0 10.1 Dellon ES, Aderoju A, Woosley JT, Sandler RS, Shaheen NJ (October 2007). "Variability in diagnostic criteria for eosinophilic esophagitis: a systematic review". Am. J. Gastroenterol. 102 (10): 2300–13. doi:10.1111/j.1572-0241.2007.01396.x. PMID 17617209.
  11. Dellon, ES.; Fritchie, KJ.; Rubinas, TC.; Woosley, JT.; Shaheen, NJ. (Jul 2010). "Inter- and intraobserver reliability and validation of a new method for determination of eosinophil counts in patients with esophageal eosinophilia.". Dig Dis Sci 55 (7): 1940-9. doi:10.1007/s10620-009-1005-z. PMID 19830560.
  12. Furuta GT, Liacouras CA, Collins MH, et al. (October 2007). "Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment". Gastroenterology 133 (4): 1342–63. doi:10.1053/j.gastro.2007.08.017. PMID 17919504.
  13. Liacouras CA, Spergel JM, Ruchelli E, et al. (December 2005). "Eosinophilic esophagitis: a 10-year experience in 381 children". Clin. Gastroenterol. Hepatol. 3 (12): 1198–206. PMID 16361045.
  14. Saffari, H.; Peterson, KA.; Fang, JC.; Teman, C.; Gleich, GJ.; Pease, LF. (Sep 2012). "Patchy eosinophil distributions in an esophagectomy specimen from a patient with eosinophilic esophagitis: Implications for endoscopic biopsy.". J Allergy Clin Immunol 130 (3): 798-800. doi:10.1016/j.jaci.2012.03.009. PMID 22502795.
  15. 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.