Herpes Simplex Virus Esophagitis


A previously healthy 29-year-old woman presented to the gastroenterology clinic with a 2-day history of painful swallowing of solids and liquids (odynophagia). One week earlier, she had had a fever and sore throat for 3 days. Physical examination was normal. Upper endoscopy revealed multiple discrete, shallow, “volcano-like” ulcers with raised edges in the middle esophagus (Panel A, arrows). In the distal esophagus, widespread whitish exudates and friable mucosa were seen (Panel B). Histopathological testing of a biopsy specimen from an ulcer showed viral cytopathic effects — including chromatin margination, nuclear molding, and multinucleation — in the squamous epithelial cells of the esophageal lining (Panel C, hematoxylin and eosin stain). Immunohistochemical staining for herpes simplex virus and testing for serum IgM antibody against herpes simplex virus were positive. Testing for human immunodeficiency virus was negative. A diagnosis of herpes simplex virus esophagitis, which is more typically seen in persons with immunocompromise, was made. The patient reported no history of herpes simplex virus infection. Treatment with intravenous acyclovir was initiated and later changed to an oral formulation when the patient’s odynophagia abated 7 days after the initiation of treatment. Results of a repeat upper endoscopy that was conducted 4 weeks after the end of treatment were normal.
Ankit Agarwal, M.D., D.M. , and Ashish Agarwal, M.D., D.M.Author
Published September 27, 2025
N Engl J Med 2025;393: e21
DOI: 10.1056/NEJMicm2502014
VOL. 393 NO. 13

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