Esophagus
Esophagitis
HSV esophagitis
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PubMed Search: Herpes simplex esophagitis
Table of Contents
Definition / general | Essential features | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Diagrams / tables | Clinical features | Diagnosis | Prognostic factors | Case reports | Treatment | Clinical images | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Videos | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Patel R, Mueller J. HSV esophagitis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/esophagusHSV.html. Accessed April 25th, 2024.
Definition / general
- Infectious esophagitis is the second most common cause of esophagitis after gastroesophageal reflux disease (GERD) (Gastroenterol Hepatol (N Y) 2013;9:517)
- The most common causes of infectious esophagitis are Candida (88%), herpes simplex virus (10%) and cytomegalovirus (2%)
- Herpes simplex virus (HSV) is the most common cause of viral esophagitis (StatPearls: Esophagitis [Accessed 10 January 2023])
Essential features
- Majority of the cases are due to reactivation of HSV1 (Case Rep Gastrointest Med 2016;2016:7603484)
- Biopsy should be performed from the margin / edge of the ulcer rather than from the base (Clin Microbiol Infect 1997;3:397)
- Confirmation of the diagnosis is obtained by histology or viral culture of esophageal specimens (Clin Microbiol Infect 1997;3:397)
- IHC stain is only required when histologic features are equivocal
- PAS or GMS stains can be performed to rule out concomitant fungal infection
Epidemiology
- HSV esophagitis occurs most frequently in immunocompromised hosts, such as:
- Solid organ and bone marrow transplant recipients
- After the prolonged use of corticosteroid or immunosuppressive drugs
- HIV / AIDS
- Self limited in immunocompetent patients
- More frequent in men than women (World J Gastroenterol 2017;23:3011)
- Incidence of 1.8% in an autopsy series (Medicine (Baltimore) 2010;89:204)
Sites
- Herpes simplex virus infection in the gastrointestinal tract primarily affects the esophagus (Medicine (Baltimore) 2016;95:e3187)
- Lower third of the esophagus is more commonly involved (68.3%); diffuse esophagitis can occur (Case Rep Gastrointest Med 2016;2016:7603484)
Pathophysiology
- More commonly occurs after reactivation of latent HSV with spread of virus to the esophageal mucosa by way of the vagus nerve or by direct extension of oral - pharyngeal infection into the esophagus (Prz Gastroenterol 2013;8:333)
- Primary HSV infection is less common
Etiology
- Most infections are related to HSV1, although HSV2 has occasionally been reported (Case Rep Gastrointest Med 2016;2016:7603484)
Clinical features
- Most common presentations are:
- Odynophagia
- Dysphagia
- Esophageal pain
- Can have coexistent herpes labialis, glossitis or oropharyngeal ulcers
- May be associated with various opportunistic diseases, such as candidiasis, CMV and Kaposi sarcoma
- Endoscopic findings include multiple discrete or coalescent small ulcers, which may be superficial, punched out or volcano-like in appearance (Case Rep Gastrointest Med 2016;2016:7603484)
Diagnosis
- Histopathological examination from the margins of the ulcers (Clin Microbiol Infect 1997;3:397)
- Endoscopic examination
- Tissue culture
- Polymerase chain reaction (PCR) to detect HSV DNA
- In situ hybridization (ISH) (Hum Pathol 1990;21:443)
- Immunohistochemistry (Appl Immunohistochem Mol Morphol 2021;29:713)
Prognostic factors
- Overall good
- Disseminated disease is rare but may be fatal
Case reports
- 17 year old immunocompetent boy with HSV esophagitis (Glob Pediatr Health 2021;8:2333794X211052914)
- 21 year old woman with HSV esophagitis presenting as dysphagia (World J Gastroenterol 2007;13:2756)
- 28 year old man with HSV2 esophagitis (Case Rep Gastrointest Med 2016;2016:7603484)
- 62 year old female ICU patient with HSV esophagitis presenting as hematochezia (ACG Case Rep J 2020;7:e00372)
Treatment
- Treatment is always indicated in immunosuppressed patients
- Acyclovir (Clin Infect Dis 1996;22:926)
- Foscarnet in cases with acyclovir resistance (Bone Marrow Transplant 1993;11:177)
Clinical images
Images hosted on other servers:
Endoscopic features
Diffuse mucosal erosions and ulcerations
Gross description
- According to macroscopic appearance, HSV esophagitis is divided into 3 types (Medicine (Baltimore) 2016;95:e3187):
- Type I: small, punched out lesions with raised margins usually coated with yellowish exudate
- Type II: small, punched out lesions but no raised margins or exudate
- Type III: multiple ulcers, with a map-like, confluent appearance over the entire esophagus
- Typical ulcers are superficial, with size varying from a few millimeters up to 2 cm (Clin Microbiol Infect 1997;3:397)
- Most lesions are located in the middle to distal esophagus (Medicine (Baltimore) 2016;95:e3187)
- Nonulcerated erythematous mucosa and pseudomembranes have been noted occasionally
- See Diagrams / tables for gross appearance versus endoscopic images
Gross images
Images hosted on other servers:
Punched out ulcers
Microscopic (histologic) description
- Typical histologic findings are only present at the edge of the ulcer (Clin Microbiol Infect 1997;3:397)
- Early lesions show nuclear swelling of keratinocytes and individual cell necrosis
- Ulcer bed demonstrates prominent necrosis and acute inflammatory cell infiltrate
- Marked mononuclear cell infiltrate adjacent to the infected squamous epithelium
- Infected squamous epithelial cells show 3 Ms:
- Molding of nuclear contours
- Margination of chromatin to the periphery of nuclei
- Multinucleation
- Intranuclear inclusions:
- Cowdry type A: acidophilic inclusion with surrounding clear halo
- Equivocal cases require an HSV immunohistochemical (IHC) stain to confirm the diagnosis
Microscopic (histologic) images
Contributed by James Mueller, M.D., Ph.D.
Esophageal biopsy
Prominent acute inflammation
Cowdry A inclusion
3 Ms
Multinucleation
Glassy chromatin
Edge of the ulcer
Viral cytopathic effect
HSV IHC stain
Positive stains
- HSV complex (HSV1 and HSV2) IHC stain: stains infected squamous epithelial cells
Negative stains
- CMV IHC stain
- VZV IHC stain
- PAS special stain (Clin Microbiol Infect 1997;3:397)
- GMS special stain
Videos
Overview of HSV esophagitis
Gross and histopathologic findings of HSV esophagitis
Sample pathology report
- Esophagus, biopsy:
- HSV esophagitis
Differential diagnosis
- CMV esophagitis:
- More commonly presents as a single, isolated and deep, large ulcer rather than multiple small, shallow ulcerations as in HSV esophagitis
- Intranuclear and intracytoplasmic inclusions are more common in mesenchymal and endothelial cells than epithelial cells
- Positive CMV IHC stain
- Negative HSV IHC stain
- Herpes zoster / varicella:
- Undistinguishable histologically
- Clinically, patients often have the cutaneous manifestations of chicken pox or shingles
- Positive VZV IHC stain
- Negative HSV IHC stain
- Candida esophagitis:
- Varicella zoster virus (VZV) esophagitis (Am J Surg Pathol 2021;45:209):
- Viral cytopathic changes are similar to HSV, but it is often pronounced in peripapillary epithelium as compared to superficial epithelium in HSV esophagitis
- Esophageal ulcers are more hemorrhagic and less inflammatory as compared to HSV
- Clinically, patients often have the cutaneous manifestations of chicken pox or shingles
- Positive VZV IHC stain
- Negative HSV IHC stain
Additional references
Board review style question #1
A patient who underwent liver transplantation had a recent episode of Candida esophagitis treated with fluconazole. Symptoms of pain and dysphagia persisted and repeat endoscopy showed multiple sharply demarcated and superficial ulcers ranging from 2 mm to 2 cm. What is the biopsy diagnosis?
- Cytomegalovirus (CMV) esophagitis
- Herpes simplex virus (HSV) esophagitis
- Nonspecific ulcer
- Recurrent or persistent Candida esophagitis
Board review style answer #1
B. HSV esophagitis. The latter image shows the classic histologic findings of herpes esophagitis, including molding of nuclei, margination of nuclear chromatin and multinucleation. CMV infected cells are large and show distinctive intranuclear inclusions in mesenchymal cells. Candida esophagitis shows pseudohyphae or budding spores.
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Board review style question #2
A 63 year old woman presented with dysphagia and esophageal ulcers. The image above shows a section stained with a polyclonal antibody to herpes simplex virus type 1 (HSV1). Which of the following statements about HSV immunohistochemistry is true?
- Immunohistochemistry is more sensitive and specific than in situ hybridization for HSV1 and HSV2
- The section is likely to react with anti-HSV2 antibody because of cross reactivity
- The section is likely to stain positively with an anti-HSV2 antibody because a combined HSV1 and HSV2 infection is common
- The section is not likely to stain with an anti-HSV2 antibody because a combined infection with HSV1 and HSV2 is uncommon
Board review style answer #2
B. The section is likely to react with anti-HSV2 antibody because of cross reactivity. Immunohistochemistry of HSV is useful when histology is equivocal. Most antibodies stain both HSV1 and HSV2 precluding reliable identification of the specific HSV. In situ hybridization allows the distinction of HSV1 and HSV2 but is more labor intensive. HSV antibodies may weakly cross react with varicella zoster virus (VZV) but this is usually not a problem.
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