Skip to main content

Advertisement

SpringerLink
Log in

Esophagitis unrelated to reflux disease: current status and emerging diagnostic challenges

  • Invited Annual Review Issue
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

There has been much progress in our understanding of esophageal inflammatory disorders in the past few years. This is particularly true about esophageal eosinophilia and PPI responsiveness, lymphocytic esophagitis and motility disorders, and short-term risk of neoplasia in esophageal leukoplakia. The current review will summarize esophageal injury patterns that primarily occur due to non-reflux causes, with a focus on usual pitfalls in biopsy diagnosis and recent advances in our knowledge of the more common forms of esophagitis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13
Fig. 14
Fig. 15
Fig. 16
Fig. 17
Fig. 18

Similar content being viewed by others

Reference

  1. Wishingrad M (1999) Sexually transmitted esophagitis: primary herpes simplex virus type 2 infection in a healthy man. Gastrointest Endosc 50(6):845–846

    Article  CAS  PubMed  Google Scholar 

  2. Maiorana A et al (2003) Human cytomegalovirus infection of the gastrointestinal tract in apparently immunocompetent patients. Hum Pathol 34(12):1331–1336

    Article  PubMed  Google Scholar 

  3. Chen Z, Scudiere JR, Montgomery E (2009) Medication-induced upper gastrointestinal tract injury. J Clin Pathol 62(2):113–119

    Article  CAS  PubMed  Google Scholar 

  4. Parfitt JR, Driman DK (2007) Pathological effects of drugs on the gastrointestinal tract: a review. Hum Pathol 38(4):527–536

    Article  CAS  PubMed  Google Scholar 

  5. Abraham SC, Yardley JH, Wu TT (1999) Erosive injury to the upper gastrointestinal tract in patients receiving iron medication: an underrecognized entity. Am J Surg Pathol 23(10):1241–1247

    Article  CAS  PubMed  Google Scholar 

  6. Lee FD (1994) Drug-related pathological lesions of the intestinal tract. Histopathology 25(4):303–308

    Article  CAS  PubMed  Google Scholar 

  7. Boyce HW Jr (1998) Drug-induced esophageal damage: diseases of medical progress. Gastrointest Endosc 47(6):547–550

    Article  PubMed  Google Scholar 

  8. Graham DY (2002) What the gastroenterologist should know about the gastrointestinal safety profiles of bisphosphonates. Dig Dis Sci 47(8):1665–1678

    Article  CAS  PubMed  Google Scholar 

  9. de Groen PC et al (1996) Esophagitis associated with the use of alendronate. N Engl J Med 335(14):1016–1021

    Article  PubMed  Google Scholar 

  10. Abraham SC et al (1999) Alendronate-associated esophageal injury: pathologic and endoscopic features. Mod Pathol 12(12):1152–1157

    CAS  PubMed  Google Scholar 

  11. Millar AJ, Cox SG (2015) Caustic injury of the oesophagus. Pediatr Surg Int 31(2):111–121

    Article  PubMed  Google Scholar 

  12. Uygun I et al (2012) Clinico-epidemiological study of caustic substance ingestion accidents in children in Anatolia: the DROOL score as a new prognostic tool. Acta Chir Belg 112(5):346–354

    Article  CAS  PubMed  Google Scholar 

  13. Kay M, Wyllie R (2009) Caustic ingestions in children. Curr Opin Pediatr 21(5):651–654

    Article  PubMed  Google Scholar 

  14. Riffat F, Cheng A (2009) Pediatric caustic ingestion: 50 consecutive cases and a review of the literature. Dis Esophagus 22(1):89–94

    Article  CAS  PubMed  Google Scholar 

  15. Purdy JK, Appelman HD, McKenna BJ (2012) Sloughing esophagitis is associated with chronic debilitation and medications that injure the esophageal mucosa. Mod Pathol 25(5):767–775

    Article  PubMed  Google Scholar 

  16. Carmack SW et al (2009) Esophagitis dissecans superficialis (“sloughing esophagitis”): a clinicopathologic study of 12 cases. Am J Surg Pathol 33(12):1789–1794

    Article  PubMed  Google Scholar 

  17. Trabulo D et al (2015) Esophageal stenosis with sloughing esophagitis: a curious manifestation of graft-vs-host disease. World J Gastroenterol 21(30):9217–9222

    Article  PubMed  PubMed Central  Google Scholar 

  18. Baum S, Sakka N, Artsi O et al (2014 Apr-May) Diagnosis and classification of autoimmune blistering diseases. Autoimmun Rev 13(4–5):482–489

    Article  CAS  PubMed  Google Scholar 

  19. Goldberg NS, Weiss SS (1989 Nov) Pemphigus vulgaris of the esophagus in women. J Am Acad Dermatol 21(5 Pt 2):1115–1118

    Article  CAS  PubMed  Google Scholar 

  20. Ahmadi B, DePasquale JR (2003) Esophageal bullous pemphigoid. Am J Gastroenterol 98:S214–S215

    Google Scholar 

  21. Chang S, Park SJ, Kim SW et al (2014 Sep) Esophageal involvement of Pemphigus vulgaris associated with upper gastrointestinal bleeding. Clin Endosc 47(5):452–454

    Article  PubMed  PubMed Central  Google Scholar 

  22. Kia L, Hirano I (2015) Distinguishing GERD from eosinophilic oesophagitis: concepts and controversies. Nat Rev Gastroenterol Hepatol 12(7):379–386

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Liacouras CA et al (2011) Eosinophilic esophagitis: updated consensus recommendations for children and adults. J Allergy Clin Immunol 128(1):3–20 e6 quiz 21-2

    Article  PubMed  Google Scholar 

  24. Straumann A et al (2012) Pediatric and adult eosinophilic esophagitis: similarities and differences. Allergy 67(4):477–490

    Article  CAS  PubMed  Google Scholar 

  25. Furuta GT et al (2007) Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology 133(4):1342–1363

    Article  CAS  PubMed  Google Scholar 

  26. Molina-Infante J et al (2011) Esophageal eosinophilic infiltration responds to proton pump inhibition in most adults. Clin Gastroenterol Hepatol 9(2):110–117

    Article  CAS  PubMed  Google Scholar 

  27. Wen T et al (2015) Transcriptome analysis of proton pump inhibitor-responsive esophageal eosinophilia reveals proton pump inhibitor-reversible allergic inflammation. J Allergy Clin Immunol 135(1):187–197

    Article  CAS  PubMed  Google Scholar 

  28. Dellon ES et al (2013) Clinical and endoscopic characteristics do not reliably differentiate PPI-responsive esophageal eosinophilia and eosinophilic esophagitis in patients undergoing upper endoscopy: a prospective cohort study. Am J Gastroenterol 108(12):1854–1860

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Moawad FJ et al (2013) Randomized controlled trial comparing aerosolized swallowed fluticasone to esomeprazole for esophageal eosinophilia. Am J Gastroenterol 108(3):366–372

    Article  CAS  PubMed  Google Scholar 

  30. Molina-Infante J et al (2014) Proton pump inhibitor-responsive oesophageal eosinophilia correlates with downregulation of eotaxin-3 and Th2 cytokines overexpression. Aliment Pharmacol Ther 40(8):955–965

    Article  CAS  PubMed  Google Scholar 

  31. Iwakura N et al (2015) Basophil infiltration in eosinophilic oesophagitis and proton pump inhibitor-responsive oesophageal eosinophilia. Aliment Pharmacol Ther 41(8):776–784

    Article  CAS  PubMed  Google Scholar 

  32. Warners MJ et al (2015) PPI-responsive esophageal eosinophilia cannot be distinguished from eosinophilic esophagitis by endoscopic signs. Eur J Gastroenterol Hepatol 27(5):506–511

    Article  PubMed  Google Scholar 

  33. Hirano I et al (2013) Endoscopic assessment of the oesophageal features of eosinophilic oesophagitis: validation of a novel classification and grading system. Gut 62(4):489–495

    Article  PubMed  CAS  Google Scholar 

  34. Collins MH (2014) Histopathologic features of eosinophilic esophagitis and eosinophilic gastrointestinal diseases. Gastroenterol Clin N Am 43(2):257–268

    Article  Google Scholar 

  35. Sayej WN et al (2009) Treatment with high-dose proton pump inhibitors helps distinguish eosinophilic esophagitis from noneosinophilic esophagitis. J Pediatr Gastroenterol Nutr 49(4):393–399

    Article  CAS  PubMed  Google Scholar 

  36. Isomoto H et al (2004) Mucosal concentrations of proinflammatory cytokines and chemokines at gastric cardia: implication of Helicobacter pylori infection and gastroesophageal reflux. Am J Gastroenterol 99(6):1063–1068

    Article  CAS  PubMed  Google Scholar 

  37. Wen T et al (2013) Molecular diagnosis of eosinophilic esophagitis by gene expression profiling. Gastroenterology 145(6):1289–1299

    Article  CAS  PubMed  Google Scholar 

  38. Peterson KA et al (2010) Comparison of esomeprazole to aerosolized, swallowed fluticasone for eosinophilic esophagitis. Dig Dis Sci 55(5):1313–1319

    Article  PubMed  Google Scholar 

  39. Lucendo AJ, Arias A, and Molina-Infante J (2016) Efficacy of Proton Pump Inhibitor Drugs for Inducing Clinical and Histologic Remission in Patients With Symptomatic Esophageal Eosinophilia: A Systematic Review and Meta-Analysis. Clin Gastroenterol Hepatol 14(1): p. 13-22 e1

    Article  CAS  PubMed  Google Scholar 

  40. Rubio CA, Sjodahl K, Lagergren J (2006) Lymphocytic esophagitis: a histologic subset of chronic esophagitis. Am J Clin Pathol 125(3):432–437

    Article  PubMed  Google Scholar 

  41. Haque S, Genta RM (2012) Lymphocytic oesophagitis: clinicopathological aspects of an emerging condition. Gut 61(8):1108–1114

    Article  PubMed  Google Scholar 

  42. Purdy JK et al (2008) Lymphocytic esophagitis: a chronic or recurring pattern of esophagitis resembling allergic contact dermatitis. Am J Clin Pathol 130(4):508–513

    Article  PubMed  Google Scholar 

  43. Xue Y et al (2015) Lymphocytic esophagitis with CD4 T-cell-predominant intraepithelial lymphocytes and primary esophageal motility abnormalities: a potential novel clinicopathologic entity. Am J Surg Pathol 39(11):1558–1567

    Article  PubMed  Google Scholar 

  44. Rubio CA, Ichiya T, Schmidt PT (2017 Mar) Lymphocytic oesophagitis, eosinophilic oesophagitis and compound lymphocytic-eosinophilic oesophagitis I: histological and immunohistochemical findings. J Clin Pathol 70(3):208–216

    Article  CAS  PubMed  Google Scholar 

  45. Ebach DR et al (2011) Lymphocytic esophagitis: a possible manifestation of pediatric upper gastrointestinal Crohn’s disease. Inflamm Bowel Dis 17(1):45–49

    Article  PubMed  Google Scholar 

  46. Sutton LM et al (2014) Lymphocytic esophagitis in children. Inflamm Bowel Dis 20(8):1324–1328

    Article  PubMed  Google Scholar 

  47. Cohen S et al (2012) Lymphocytic esophagitis: a diagnosis of increasing frequency. J Clin Gastroenterol 46(10):828–832

    Article  PubMed  PubMed Central  Google Scholar 

  48. Basseri B et al (2013) Evaluation of peripapillary lymphocytosis and lymphocytic esophagitis in adult inflammatory bowel disease. Gastroenterol Hepatol (N Y) 9(8):505–511

    Google Scholar 

  49. Putra J et al (2016) Lymphocytic esophagitis in nonachalasia primary esophageal motility disorders: improved criteria, prevalence, strength of association, and natural history. Am J Surg Pathol 40(12):1679–1685

    Article  PubMed  PubMed Central  Google Scholar 

  50. Zerbib F, Roman S (2015) Current therapeutic options for esophageal motor disorders as defined by the Chicago Classification. J Clin Gastroenterol 49(6):451–460

    Article  CAS  PubMed  Google Scholar 

  51. Scully C, el-Kom M (1985) Lichen planus: review and update on pathogenesis. J Oral Pathol 14(6):431–458

    Article  CAS  PubMed  Google Scholar 

  52. Lund WS (1976) Treatment of superficial lesions of the mouth and pharynx. J Laryngol Otol 90(1):105–112

    Article  CAS  PubMed  Google Scholar 

  53. Abraham SC et al (2000) Esophageal lichen planus: case report and review of the literature. Am J Surg Pathol 24(12):1678–1682

    Article  CAS  PubMed  Google Scholar 

  54. Chryssostalis A et al (2008) Esophageal lichen planus: a series of eight cases including a patient with esophageal verrucous carcinoma. A case series. Endoscopy 40(9):764–768

    Article  CAS  PubMed  Google Scholar 

  55. Quispel R et al (2009) High prevalence of esophageal involvement in lichen planus: a study using magnification chromoendoscopy. Endoscopy 41(3):187–193

    Article  CAS  PubMed  Google Scholar 

  56. Salaria SN et al (2013) Lichenoid esophagitis: clinicopathologic overlap with established esophageal lichen planus. Am J Surg Pathol 37(12):1889–1894

    Article  PubMed  Google Scholar 

  57. Katzka DA et al (2010) Variations in presentations of esophageal involvement in lichen planus. Clin Gastroenterol Hepatol 8(9):777–782

    Article  PubMed  Google Scholar 

  58. Silverman S Jr, Gorsky M, Lozada-Nur F (1985) A prospective follow-up study of 570 patients with oral lichen planus: persistence, remission, and malignant association. Oral Surg Oral Med Oral Pathol 60(1):30–34

    Article  PubMed  Google Scholar 

  59. Silverman S Jr et al (1991) A prospective study of findings and management in 214 patients with oral lichen planus. Oral Surg Oral Med Oral Pathol 72(6):665–670

    Article  PubMed  Google Scholar 

  60. Briggs GW (1961) Amyloidosis. Ann Intern Med 55:943–957

    Article  CAS  PubMed  Google Scholar 

  61. Tada S et al (1990) Endoscopic and biopsy findings of the upper digestive tract in patients with amyloidosis. Gastrointest Endosc 36(1):10–14

    Article  CAS  PubMed  Google Scholar 

  62. Costigan DJ, Clouse RE (1983) Achalasia-like esophagus from amyloidosis. Successful treatment with pneumatic bag dilatation. Dig Dis Sci 28(8):763–765

    Article  CAS  PubMed  Google Scholar 

  63. Lazaraki G et al (2009) A rare case of multiple myeloma initially presenting with pseudoachalasia. Dis Esophagus 22(6):E21–E24

    Article  PubMed  Google Scholar 

  64. Rubinow A et al (1983) Esophageal manometry in systemic amyloidosis. A study of 30 patients. Am J Med 75(6):951–956

    Article  CAS  PubMed  Google Scholar 

  65. Ip S et al (2016) Sensitivities of biopsy sites in the endoscopic evaluation of graft-versus-host disease: retrospective review from a tertiary center. Dig Dis Sci 61(8):2351–2356

    Article  PubMed  Google Scholar 

  66. Novak JM et al (1979) Effects of radiation on the human gastrointestinal tract. J Clin Gastroenterol 1(1):9–39

    Article  CAS  PubMed  Google Scholar 

  67. Seaman WB, Ackerman LV (1957) The effect of radiation on the esophagus; a clinical and histologic study of the effects produced by the betatron. Radiology 68(4):534–541

    Article  CAS  PubMed  Google Scholar 

  68. Taggart MW et al (2013) Oesophageal hyperkeratosis: clinicopathological associations. Histopathology 63(4):463–473

    PubMed  Google Scholar 

  69. Kaye MD (1987) Esophageal leukoplakia. Gastrointest Endosc 33(3):254–259

    Article  CAS  PubMed  Google Scholar 

  70. Singhi AD et al (2014) Esophageal leukoplakia or epidermoid metaplasia: a clinicopathological study of 18 patients. Mod Pathol 27(1):38–43

    Article  PubMed  Google Scholar 

  71. Ezoe Y et al (2011) Epidermoid metaplasia of the esophagus: endoscopic feature and differential diagnosis. Hepato-Gastroenterology 58(107–108):809–813

    PubMed  Google Scholar 

  72. Postlethwait RW, Musser AW (1974) Changes in the esophagus in 1,000 autopsy specimens. J Thorac Cardiovasc Surg 68(6):953–956

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, Weill Cornell Medical College, New York, NY, USA

    Melanie E. Johncilla

  2. Department of Pathology, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA, 02115, USA

    Amitabh Srivastava

Authors
  1. Melanie E. Johncilla
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Amitabh Srivastava
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Amitabh Srivastava.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

The authors declare that all work meets the ICMJE recommendation for qualification of authorship. (Invited Review)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Johncilla, M.E., Srivastava, A. Esophagitis unrelated to reflux disease: current status and emerging diagnostic challenges. Virchows Arch 472, 29–41 (2018). https://doi.org/10.1007/s00428-017-2238-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-017-2238-4

Keywords

Search

Navigation