Herpes simplex virus (HSV) esophagitis (HSE) is classically associated with immunocompromised states, whereas eosinophilic esophagitis (EoE) is a chronic immune-mediated condition characterized by esophageal eosinophilic inflammation. We present an unusual case of HSV esophagitis as the initial manifestation leading to the diagnosis of EoE in a previously healthy adolescent.

A 17-year-old male with no history of atopy, food allergies, or immunodeficiency presented with fever and odynophagia of two days duration. At admission, an upper endoscopy was performed which revealed multiple well-demarcated, punched-out ulcers with fibrin exudate along the mid and distal esophagus from which biopsied were obtained.  Physical examination was unremarkable, and laboratory results, including HIV and immunologic screening, were within normal limits except from an elevated C-reactive protein value. Biopsies demonstrated viral cytopathic changes consistent with HSV infection, while HSV IgM serology was negative. The patient was treated with oral valacyclovir at a dose 1000mg twice daily for  10 days, with rapid clinical improvement and complete symptom resolution.

One month later, follow-up endoscopy was performed to confirm mucosal healing. The ulcers had completely resolved. Surprisingly, new findings of esophageal rings and longitudinal furrows were observed throughout the esophagus. Biopsies from mid and proximal esophagus revealed dense eosinophilic infiltration exceeding 150 eosinophils per high-power field, confirming a diagnosis of eosinophilic esophagitis. The patient was started on high-dose proton pump inhibitor (PPI) therapy After two months of treatment, repeat biopsies showed reduction of eosinophilic infiltration (<15 eosinophils per high-power field)

This case illustrates an uncommon sequence in which HSE preceded the diagnosis of EoE in an immunocompetent patient. The relationship between these two entities remains uncertain, but several hypotheses have been proposed. HSV infection may act as a trigger for local mucosal immune activation, leading to eosinophilic inflammation and unmasking a latent predisposition to EoE. Alternatively, an underlying EoE-related epithelial barrier dysfunction might predispose to viral infections. Regardless of the mechanism, this case emphasizes the importance of follow-up endoscopy after HSE, even in immunocompetent individuals.