Herpes Simplex Virus and the Alimentary Tract
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Herpes Simplex Virus and the Alimentary Tract Eric A. Lavery, MD , and Walter J. Coyle , MD Corresponding author infections of the gastrointestinal tract in both immuno- Walter J. Coyle, MD Division of Gastroenterology and Hepatology Scripps Clinic compromised and immunocompetent patients. Torrey Pines, 10666 North Torrey Pines Road, N203, La Jolla, CA 92037, USA. E-mail: [email protected] Background Current Gastroenterology Reports 2008, 10: 417– 423 HSV is a member of the Herpesviridae family of viruses, Current Medicine Group LLC ISSN 1522-8037 which also includes varicella zoster virus (VZV), cyto- Copyright © 2008 by Current Medicine Group LLC megalovirus (CMV), Epstein-Barr virus (EBV), and human herpesvirus (HHV) 6, 7, and 8 [ 2• ]. Members of this family contain linear, double-stranded DNA within a Herpes simplex virus (HSV) infection is well known as protein capsid, which is surrounded by a tegument and an a sexually transmitted disease. However, relatively little outer glycoprotein layer [ 2• , 3•• ]. HSV-1 and HSV-2 have has been published concerning the presentations and 70% genomic homology but tend to affect different areas treatment of HSV infection within the gastrointestinal of the body. HSV-1 tends to cause most oral and esopha- tract, where HSV most commonly affects the esophagus geal herpetic lesions; it is commonly acquired during in both immunocompromised and immunocompetent childhood, though it has been associated with proctitis in patients. HSV proctitis is not uncommon and occurs a minority of cases. HSV-1 is primarily transmitted via primarily in males having sex with males. In patients oral secretions and has a higher seroprevalence in lower with normal immune systems, gastrointestinal HSV socioeconomic communities. HSV-2 is most often sexu- infections are generally self-limited and rarely require ally transmitted; it primarily causes genital and rectal antiviral therapy. Treatment of infection is suggested infections. Estimates suggest that HSV-1 has a worldwide for immunocompromised patients, though no large seroprevalence of 80% to 90%, whereas HSV-2 has a 22% randomized controlled trials have been performed. seroprevalence rate in the United States [ 3••, 4 ]. However This article reviews the manifestations of HSV infection among patients infected with HIV, HSV is the most com- within the luminal gastrointestinal tract and options for mon viral coinfection, and 95% of males who have sex diagnosis and treatment. with males (MSM) are seropositive for HSV-1, HSV-2, or both [ 4 ]. Incubation periods for primary HSV infections range from 2 to 12 days [ 5 ]. Introduction Primary infections, diagnosed by antibody serocon- Herpes simplex virus (HSV) infection is common version or a fourfold rise in HSV IgG levels between acute throughout the world, with both HSV-1 and HSV-2 and convalescent serum antibody titers, may produce infections being well documented, especially in immuno- constitutional symptoms but are frequently asymptomatic compromised patients. Abundant literature exists [ 2• ]. After primary infection, viral particles are trans- concerning HSV-2 genital infections and HSV-1 oro- ported retrograde from the peripheral site of infection to labial infections in immunocompetent patients, but the dorsal root ganglia via nerve axons [ 3•• ]. The virus may medical literature includes relatively little information become latent for an unpredictable period. At any time, related to HSV infections of the gastrointestinal tract. the virus may be reactivated, traveling from the ganglia Increasingly, case reports, case series, and reviews have through sensory neurons and replicating in the target shown HSV to be an infrequent cause of gastrointesti- cells. Asymptomatic reactivation (recurrence) may cause nal infections in immunocompetent hosts. In addition, viral shedding; symptomatic reactivation (recrudescence) HSV has been investigated as a possible cause of gastro- frequently causes symptoms that are less severe and intestinal conditions such as peptic ulcer disease (PUD), shorter in duration than the symptoms of the primary toxic megarectum, and achalasia [ 1 ]. The purpose of this infection but that have a similar distribution. Most cases review is to summarize the available literature on HSV of gastrointestinal HSV infection in immunocompromised 418 Gastrointestinal Infections (44.7%). Almost one quarter of patients have preceding cough or sore throat; 27% have oral lesions, and 13% have herpetic skin rashes [ 6 ]. Hematemesis is unusual in HSV esophagitis, though it has been reported in several case reports [ 9 , 10 ]. The incidence of HSV esophagitis by gender depends upon age [ 6 , 8]. In a review of 38 cases of HSV esophagitis in immunocompetent hosts, the mean age of presentation was 28.5 ± 20.4 years. Almost 79% of those affected were younger than 40, and of these, 76% were male [ 8]. Above the age of 40, however, there was no gender predilection. Although the esophagus is the most common site of HSV infection in the gastrointestinal tract, autopsy data suggest that HSV esophagitis is uncommon overall. In one Japanese autopsy series, it was found in 24 (1.8%) of 1307 serial autopsies [ 11]. In a separate Japanese autopsy series of 145 cases, 9 patients (6%) were found to have HSV esophagitis [12 ]. This diagnosis was based on the macroscopic appearance of esophageal erosions or ulcer- ations and positive immunohistochemical staining. All affected patients were immunocompromised: eight had a Figure 1 . Herpes simplex virus esophagitis with ulcerations. Endo- malignancy and the ninth was using steroid therapy for scopic view of the distal esophagus with mucosal ulceration typical rheumatoid arthritis. All these patients had HSV-1 as for herpes simplex virus infection. (Courtesy of Glen Arluk, MD.) the etiologic agent. Consistent with the Japanese autopsy series, the vast majority of documented cases of HSV patients represent recrudescence, as these patients have esophagitis are due to HSV-1, though at least one case higher baseline seroprevalence rates. Primary infection report documents HSV-2 esophagitis secondary to hetero- is the most common cause of HSV gastrointestinal infec- sexual orogenital contact in an immunocompetent patient tions in those who are immunocompetent. The underlying [ 7 , 13 ]. One Western autopsy series reviewed 3000 consec- mechanism for reactivation is unknown, but multiple utive autopsies, of which only 55 had microscopic slides factors have been suggested, including stress, immuno- of esophageal ulcers. Of these, 14 were consistent with suppression, and sun exposure. HSV (based on histologic appearance), giving an overall prevalence of HSV esophagitis of about 0.5% [14 ]. In immunocompetent patients, the distal esophagus is Esophagus involved 64% of the time, making it the most frequently Within the gastrointestinal tract, HSV involvement is affected esophageal location [ 8 ]. However, extensive most frequently recognized within the esophagus. In a esophageal involvement is the norm, occurring over 92% recent case report, Kato et al. [ 6 ] discussed a 26-year-old of the time. It is rare for noncontiguous regions to be immunocompetent man who presented after develop- affected with normal intervening mucosa. The endoscopic ing cough, sore throat, fever, and rash on his chest and appearance typically shows multiple ulcers, which may be abdomen. Three days later, the patient complained of superfi cial or punched out (Fig. 1 ). Friable mucosa (84.2%) odynophagia and hematemesis [6 ]. Esophagogastro- and whitish exudates (39.5%) also are commonly seen [ 8 ]. duodenoscopy (EGD) revealed multiple ulcers in the mid Although esophageal ulceration is the most common and distal esophagus and a Mallory-Weiss tear. Repeat endoscopic fi nding associated with HSV esophagitis endoscopy several days later showed whitish exudates, (occurring in 86% of immunocompetent patients), this and esophageal biopsies showed Cowdry type A inclusion fi nding is by no means specifi c for HSV. In a review of bodies in the epithelial cells. HSV IgM was elevated by 7564 endoscopies performed by a single provider, 88 day 7 with low IgG levels, and the patient was suspected patients had esophageal ulcerations, but only 1% of these of having primary HSV-1 infection. The patient recovered were attributed to HSV. Gastroesophageal refl ux disease without the use of antiviral medications. (GERD) accounted for 65%, 22% were drug induced, and This report is a typical presentation of HSV esophagitis 3% were candidal in origin [ 15 ]. GERD ulcers, though in an immunocompetent patient. Symptoms frequently frequently larger than herpetic ulcers, are also typically have an acute onset, and dysphagia is a frequent complaint distal in location. In contrast, the drug-induced ulcers [ 7 ]. Odynophagia, the most common symptom, occurs appeared in the distal esophagus only 13% of the time. in over 76% of patients [ 8]. Other common symptoms HSV esophagitis is more common in the immunocom- are retrosternal chest pain, heartburn (50%), and fever promised patient and is a defi ning illness for AIDS [16 ]. Herpes Simplex Virus and the Alimentary Tract Lavery and Coyle 419 Esophageal disease occurs in about 30% of patients with caused by other members of the Herpesviridae family HIV infection; the esophagus is the viscus most commonly (VZV, CMV), but esophageal infections with VZV or involved in disseminated HSV [ 16 , 17]. Overall, however, CMV are unusual in immunocompetent patients, making candidiasis