Herpes Simplex Esophagitis in an Immunocompetent Man

Gregory M. Johnston, MD, MS

Major, United States Army

Department of Emergency Medicine

Mark A. Denny, MD

Major, United States Army

Department of Emergency Medicine

James Howden, MD

Colonel (retired), United States Army

Chief, Department of Gastroenterology

Madigan Army Medical Center

Ft. Lewis, Wash

The views expressed in the article are those of the authors and do not reflect the official policy or position of the Department of the Army, the Department of Defense, or the US Government.

Herpes simplex virus (HSV) esophagitis is a common cause of morbidity in patients with compromised immune systems. Although HSV infection is widespread in the US population, herpetic esophagitis is rarely diagnosed in immunocompetent hosts. In such persons, the disease is often asymptomatic and self-limited.

Case Presentation

A 20-year-old man presented to the emergency department with dyspnea and pleuritic retrosternal chest pain in association with progressive odynophagia to the extent that he was unable to tolerate his own secretions. The patient described a prodrome of nausea, headache, and mild odynophagia, for which he initially sought care from his primary physician. Despite treatment with penicillin VK (Veetids) and oral analgesics, his illness continued to progress. He again consulted his primary care physician, who gave him a prescription for rabeprazole (Aciphex) for presumed reflux esophagitis. This, too, proved ineffective, and his symptoms continued to worsen.

He had no significant medical or surgical history. He denied use of tobacco, alcohol, illicit drugs, or any history of sexually transmitted disease. He was involved in a monogamous relationship of 4 months' duration but denied any HIV risk factors, and results of an HIV test performed within the past 3 months were negative. Questioning of the patient's girlfriend revealed that she had a history of recurrent, self-limited perioral lesions, with the most recent outbreak occurring within the preceding 4 to 6 weeks.

The patient's vital signs included: temperature, 103.4?F; blood pressure, 163/81 mm Hg; heart rate, 100 beats/min. Physical examination showed a mildly ill-appearing man with several tender, but only modestly enlarged, cervical lymph nodes. No oropharyngeal erythema or lesions were seen. The chest was clear to auscultation, and the heart rate was regular, without murmurs, rubs, or gallops. The chest radiograph showed no cardiopulmonary disease, and an electrocardiogram (ECG) showed no ECG abnormalities. Results of a rapid streptococcal antigen test were negative. White blood cell count and troponin were normal. The patient complained of chest pain on inspiration and expiration in association with shortness of breath, so a computed tomography scan of the chest was ordered to rule out pulmonary embolism; it too was unremarkable.

Esophagogastroduodenoscopy (EGD) revealed ulcerations and inflammation throughout the esophagus: the proximal segment had moderate inflammation, the middle segment was extensively ulcerated, and the distal segment had the least amount of damage (Figure). Serology revealed a minimal elevation of HSV immunoglobulin (Ig) G, but a significant elevation (more than 1:160) of HSV IgM antibodies. Of note, the biopsy specimens obtained during EGD proved to be nondiagnostic, because the patient was started on empiric acyclovir (Zovirax) before endoscopic sampling. Cytology on the biopsy specimens was not performed.

The patient's symptoms were alleviated with a combination of antipyretics, intravenous (IV) morphine, normal saline hydration, and a mixture of viscous lidocaine HCl (Xylocaine Viscous) and aluminum hydroxide (Alu-Tab, Amphojel, Dialume)—the venerable "GI cocktail." He was subsequently admitted to the internal medicine service and was started on empiric acyclovir for presumed HSV esophagitis, as noted above.

The patient rapidly defervesced on the empiric antiviral regimen, and his diet was steadily advanced until he was able to tolerate a mechanical soft diet on hospital day 3. He received a total of 10 days of antiviral therapy, consisting of 4 days of IV acyclovir, 5 mg/kg 3 times daily, followed by 6 days of oral valacyclovir (Valtrex), 1 g twice daily. The patient was subsequently discharged from the hospital and recovered without adverse sequelae.

Discussion

Figure—EGD showing (A) the mucosa of the proximal esophagus, which appears edematous and hemorrhagic, with grouped vesicles evident; (B) the middle esophagus mucosa, which appears cobblestoned and in which extensive areas of erosion can be seen; (C) less dramatic areas of erosion and edema in the distal esophagus.

HSV infection is ubiquitous in the United States. The third National Health and Nutrition Examination Survey (NHANES III) revealed that the prevalence of HSV type 1 (HSV-1) and HSV-2 was 68% and 21.9%, respectively, in Americans aged 12 years and older.^1,2 The epidemiologic pattern of HSV-1 in the United States appears to be shifting. Once a common disease of childhood, as is still the case in many parts of the world, acquisition of this virus has decreased among children in this country and has risen among adolescents and young adults.¹ Conditions ascribed to HSV infection, whether primary infection or reactivation of latent virus, range from self-limited cutaneous lesions to florid encephalitis. Esophagitis has previously been noted as a manifestation of HSV infection.

HSV esophagitis was first reported in 1940 by Johnson³ and is now a well-known cause of morbidity in patients with compromised immune systems.⁴ HSV frequentlyoccurs as an opportunistic infection in patients with acquired immune deficiency syndrome (AIDS) or cancer, and in those who become immunocompromised secondary to pharmacotherapy. However, despite the high prevalence of this DNA virus, the overall incidence rate of HSV esophagitis is reported to be only 1.8% in autopsy patients, most of whom have documented immune compromise.⁵

The condition is rare in those who are immunocompetent, with only 51 cases reported in the literature,⁴ possibly because most such persons remain relatively asymptomaticand have a self-limited clinical course. Patients who present because of worsening symptoms may therefore represent a minority who, for unknown reasons, experience progression of the disease process. Immunocompetent persons who do present for care are typically male and are younger than age 40 years, and serology usually identifies HSV-1 as the predominant etiologic agent.^4,6 A single case of HSV-2 esophagitis in an immunocompetent person has also been reported.⁷

The majority of symptomatic immunocompetent patients with HSV esophagitis will present with an acute onset of esophageal complaints, but a subset of patients (24%) will present with a prodrome of symptoms, including odynophagia (in 76% of patients), and fever (in 44%-63%).^4,6 Other common complaints associated with HSV esophagitis include:

• Retrosternal pain
• Heartburn
• Dysphagia
• Poor oral intake.

Lesions that can be readily visualized, such as on the skin or mouth, are uncommon. A 2005 study showed that only 13% of immunocompetent patients had herpetic skin lesions, and 27% had intraoral lesions.^4,6 More unusual manifestations of this condition, such as intractable singultus, have also been reported.⁸

Treatment with the nucleoside analog acyclovir has been shown to be effective for HSV esophagitis.⁹ Treatment with acyclovir expedites the resolution of symptoms.The duration of illness ranges from 4 to 9 days in those receiving antiviral therapy compared with 10 to 17 days in those receiving symptomatic treatment alone.⁵ Although HSV esophagitis is noted to be a self-limited condition, cases of immunocompetent patients experiencing significant complications, including gastrointestinal bleeding and esophageal perforation, have been reported.^10,11

Definitive diagnosis of HSV esophagitis requires endoscopic visualization and, ideally, biopsy of mucosal lesions. Characteristic endoscopic findings typically involve the middle and distal esophagus, but the entire length of the esophagus may be affected. The esophageal mucosa will have a friable appearance, with extensive ulceration, as seen in this patient.⁴ Microscopic examination of biopsy specimens may reveal distinctive Cowdry type A intranuclear inclusions.

Conclusion

As our case demonstrates, HSV esophagitis, although a known cause of morbidity in patients with compromised immune systems, can also occur in immunocompetent hosts, who will typically present with fever and an abrupt onset of esophageal complaints. The condition is usually self-limited, but significant complications can occur. Treatment with acyclovir will hasten resolution of the illness, but opinions are divided as to whether antiviral treatment is necessary. Diagnosis of this condition in the emergency department is problematic because of the potential for significant complications; it is important for the emergency medicine physician to consult a gastroenterologist for endoscopic visualization and tissue sampling. This condition should, however, be suspected in any person who presents with fever and an acute onset of symptoms attributable to esophagitis that does not have a predisposing cause. Patients whose appearance necessitates hospitalization may benefit from empiric therapy with acyclovir before definitive diagnosis.

References

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