An Unusual Cause of Odynophagia in a Patient With Eosinophilic Esophagitis

Abstract

Question: An 18-year-old white man presented with 3 days of epigastric pain, odynophagia, vomiting, and fevers. He also reported 4 months of dysphagia with solids. His history included heartburn, allergic rhinitis, and wheat allergy. There was no personal or family history of recent infection. On admission, he was febrile (101.8°F) and tachycardic (110 bpm). Physical examination revealed a 2-mm ulcer in the lower lip and epigastric tenderness. Blood counts, biochemistry, and liver function tests were normal. Esophagogastroduodenoscopy (EGD) revealed esophagitis with multiple discrete shallow round, 3- to 4-mm ulcers starting in upper esophagus and distributed throughout its circumference (Figure A, B). Histopathology revealed necroinflammatory tissue and squamous epithelium with intercellular edema, basal zone hyperplasia, and up to 56 eosinophils per high-power field (Figure C). Immunoperoxidase staining was negative for herpes simplex virus (HSV) and cytomegalovirus. Serum HSV antibodies, HIV, and cytomegalovirus polymerase chain reaction were negative. The histologic findings were interpreted as eosinophilic esophagitis (EoE) and treatment with pantoprazole was administered. Odynophagia persisted and repeated EGD at day 5 showed persistent coalescent esophageal ulcers along with white exudates and erythema (Figure D). Several specimens were obtained from the edge of the biopsy. A representative histopathology is shown (Figure E, F). What is the diagnosis? Look on page 38 for the answer and see the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Histopathology revealed marked inflammation and viral cytopathic changes. Immunohistochemistry showed broad reactivity for HSV types I and II (Figure G). Further investigation of cell and humoral immunity was normal. The patient was treated with intravenous acyclovir with resolution of odynophagia within 3 days and then completed 14 days with valacyclovir. At 3 months on therapy with pantoprazol, dysphagia had improved and further endoscopy was normal but random biopsies revealed persistence of mucosal eosinophilia. A final diagnosis of herpetic esophagitis (HE) with concurrent EoE was made. Since its first description in 1940, close to 60 cases of HE have been well-documented in immunocompetent adults and adolescents.1Canalejo Castrillero E. Garcia Duran F. Cabello N. et al.Herpes esophagitis in healthy adults and adolescents: report of 3 cases and review of the literature.Medicine (Baltimore). 2010; 89: 204-210Crossref PubMed Scopus (77) Google Scholar HE usually affects young men. Prodromal symptoms of upper respiratory tract infection and concurrent orolabial lesions can be present. The most common clinical manifestations include acute onset of odynophagia, retrosternal pain, fever, and dysphagia. EGD reveals multiple, coalescent or discrete, small ulcers in most patients. The diagnosis can be confirmed by histopathology, viral culture, or polymerase chain reaction detection of biopsies taken from the edge of the ulcers or esophageal brush. Despite the initial negative histopathology in our patient, high clinical suspicion prompted further endoscopic evaluation, which led to the final diagnosis. Antiviral therapy on immunocompetent patients remains debatable. The pathogenesis of HE in the immunocompetent host is not entirely understood. EoE has been linked to the occurrence of HSV esophagitis in previous case reports.2Squires K.A. Cameron D.J. Oliver M. et al.Herpes simplex and eosinophilic oesophagitis: the chicken or the egg?.J Pediatr Gastroenterol Nutr. 2009; 49: 246-250Crossref PubMed Scopus (37) Google Scholar, 3Zaja Franulovic O. Lesar T. Busic N. et al.Herpes simplex primo-infection in an immunocompetent host with eosinophilic esophagitis.Pediatr Int. 2013; 55: e38-e41Crossref PubMed Scopus (20) Google Scholar In addition to local mucosal injury, dysregulation of T-helper 2 response in EoE may lead to a breakdown in barrier function and increase susceptibility to infection with swallowed virus. Future studies are needed to clarify the apparent link between these 2 entities.