0(X)2-9270/86/8l()4-0246 THE AMERICAN JOURNAL OF GASTROENTEROLOGY Vol.81, No.4, 1986 Copyright © 1986 by Am. Coll. of Gastroenterology Primed in US.A. Herpetic Esophagitis: A Diagnostic Challenge in Immunocompromised Patients Farooq P. Agha, M.D., F.A.C.G., Horchang H. Lee, M.D., M.P.H., and Timothy T. Nostrant, M.D. Department of Radiology, and Internal Medicine-Division of Gastroenterology. University of Michigan Hospitals and Medical Center, Ann Arbor. Michigan Viral esophageal infection is eommon in immunocom- these patients to infections were; diffuse histiocytic promised patients. Twelve patients wi(b esopbagitis lymphoma in three, chronic granulocytic leukemia in secondary to herpes viruses are described. Odyno- two, diabetes mellitus in three, prolonged steroid ther- phagia, dysphagia, and gastrointestinal bleeding were apy in two, extensive burns in one, renal transplanta- the most eommon symptoms. Multiple infections par- tion in two, diffuse carcinomatosis in one, and acquired tieularly with Candida were present in three of the 12 immunedeficiency syndrome in one patient. All pa- cases (25%). Typical "volcano ulcers" at endoseopy and tients were immunosuppressed and usually multiple discrete diffusely scattered shallow uleers seen on dou- predisposing factors were responsible. All patients with ble contrast esophagram are highly suggestive of her- hematological malignancy had received extensive petic esophagitis. Single contrast esophagram plays no chemotherapy before the onset of herpetic infection. specific role in the diagnosis of herpetie esophagitis. An The pertinent clinical data on these 12 patients are analysis of elinieal, endoscopic, radiologieal, and path- summarized in Table I. ologieal features is presented. All patients were symptomatic at the time of diag- nosis. Odynophagia was present in 10 of 12 patients INTRODUCTION and was the predominant symptom. A sensation of food slowly moving down the esophagus after swallow- The esophagus is the most common site of gastroin- ing was reported by all patients but dysphagia was the testinal infection in the immunocompromised patients prime symptom in only two patients. Gastrointestinal (1, 2). Candida albicans and herpes simplex virus blood loss was found in three patients. Nonspecific (HSV) are the most frequently found organisms (1-4). symptoms such as anorexia, early-satiety, and nausea Other herpes viruses particularly cytomegalovirus with vomiting were also present in four patients. Fol- (CMV) have been associated with ulcerations in other low-up data showed that five patients with herpes sim- parts of the gastrointestinal tract (5-7), but only rarely plex esophagitis were treated with Acyclovir. All five cause esophageal disease (8-10). With the development patients experienced marked symptomatic improve- of effective antifunga! and antiviral treatment, discrim- ment of odynophagia within 2 wk and had no evidence ination between different infecting organisms has be- of recurrence for at least 1 yr. One of the five patients, come essential. We report on a group of 12 immuno- however, died from metastatic carcinomatosis 1 yr after compromised patients with esophageal involvement by treatment. One patient with concomitant herpes and herpes viruses (HSV and CMV) and discuss the impor- Candida esophagitis experienced symptomatic improve- tanee of and difTieulties in diagnosing herpetie esopha- ment after Nystatin treatment. One patient with CMV gitis. esophagitis did not receive any antiviral treatment and died from complications of renal and pancreatic trans- MATERIALS AND METHODS plant rejections. Thus all five patients with herpes sim- The medical, radiological, and pathological records plex virus esophagitis responded to Acyclovir therapy. of 12 patients with histopathologically proved herpetic Endoscopic fmdings esophagitis between 1979 and 1984 at the University of Michigan Hospital were reviewed. Eight of the 12 patients underwent upper gastrointes- tinal endoscopy. All eight patients had extensive esoph- RESULTS agitis predominantly involving the distal esophagus. The ulcerations were seen on a background of marked Clinical fmdings erythema and edema. Typical "volcano" or marginal There were six men and six women aged 17 to 80 yr. ulcers were seen in six of eight patients (Fig. 1), while The underlying pathological processes predisposing two patients had confluent ulcers at the gastroesopha- 246 Aprin986 HERPETIC ESOPHAGITIS 247 TABLE I Clinical Data on 12 Patients with Herpetic Esophagitis* Predisposing Symptoms Esophagram Endoscopic Treatment/ No./Paiient/Age/Sex Factors Findings Findings Diagnostic Method Outcome Comment 1 (TL) 28 F Bitaieral Odynophagia Discrete "Volcano" Brush cytology Acyclovir HSV renal punetate ulcers culture + recovered esophagitis transplants ulcers 2 (PM) 23 M Type 1 DM Odynoph^ia Nonspecific "Volcano" Brush cytology Acyclovir HSV severe DKA ulcers recovered esophagitis 3 (SM) 39 M DM Odynophagia Ulcers Discrete Brush cytology Acyclovir HSV severe DKA esophagitis ulcers culture -t- recovered esophagitis 4 (MW) 80 M Gianl cell Odynophagia ND Discrete Brush cytology Acyclovir HSV arteritis "voleano" culture + recovered esophagitis steroids ulcers therapy 5 (RP) 50 M Metastatic Odynophagia Nonspecific Conlluent Brush cytology Acyclovir HSV carcinomatosis ulcers culture + recovered From esophagitis from prostate Ca esophagitis and chemotherapy died 1 yr hormone therapy later radiation therapy 6 (DA) 74 F CLL Odynophagia ND ND Postmortem Dx Died HSV ^m negative herpetif esophagitis sepsis esophagitis chemotherapy submucosal steroids hemorrhage antibiotics 7 (WC) 17 M Extensive Odynophagia ND ND Postmortem Dx Died HSV bums herpetic ulcers esophagitis sepsis antibiotics 8 (MR) 55 M DHL Odynophagia Plaques Discrete Culture Nystatin Concomitant chemotherapy oral ulcers and ulcers and Candida improved herpes and steroids candidiasis esophagitis plaques herpes odynophagia Candida esophagitis 9 (RP) 71 F DHL Odynophagia Nonspecific ND Postmortem Dx Died Concomitant chemotherapy esophagitis herpetic ulcers herpes and steroids superinfection Candida with Candida esophagitis 10 ILV) 65 F Rheumatoid Odynophagia Nonspecific ND Postmortem Dx Died Herpes and arthritis esophagitis herpetic Candida agranuto- esophagitis esopha^tis cytosis disseminated severe candidiasis leucopenia steroid thcrapv 11 (DR) 20 F IDDM Dysphagia Ulcers Ulcers Brush CNtology Died CMV bilateral stricture plaques CMV inclusions esophagitis renal No herpes or transplants Candida found 12 (BR) 32 M AIDS Dysphagia Nonspecific Ulcers Postmortem—Dx Died CMV homosexual esophagitis plaques CMV esophagitis esophagitis disseminated CMV dis.scminated infection CMV infection • DM. diabetes mellitus: DKA. diabetes ketoacidosis; DHL. diffuse histiocytic lymphoma; [DDM, insulin-dependent diabetes mellitus: AIDS, acquired immunodeficiency syndrome: Dx. diagnosis: ND. not done; +. positive. geal junction. Infiammatory exudates were seen in all ficial tiny punctate ulcers throughout the esophagus patients. The typical "volcano ulcers" seen at endos- (Fig. 2) and a diagnosis of herpetie esophagitis was copy predicted herpetic esophagitis in six patients. Sec- suggested. The second patient who had double contrast ondary Candida infection was diagnosed in two patients esophagram showed plaques and ulcerations and the and missed in one patient with coexistent herpes infec- diagnosis of Candida and or herpes esophagitis was tion. In two patients who subsequently proved to have made. The third patient showed typical plaques and cytomegalovirus esophagitis, the endoscopic diagnosis the diagnosis of Candida esophagitis was suggested. All was herpetic esophagitis. six patients who had single contrast esophagrams dem- onstrated esophagitis with nonspecific ulcerations R adiological findings mostly in the distal third of the esophagus (Fig. "iA and Nine patients had barium esophagrams. The majority B). One patient had a stricture in the distal esophagus of patients were too sick to undergo double contrast secondary to Barrett's esophagus and developed a sec- esophagram. thus only three had satifactory double ondary HSV infection (Fig. 4/i and B). A second patient contrast esophagrams and six had single contrast stud- had a distal stricture due to chronic gastroesophageal ies. One patient demonstrated diffusely scattered super- reflux with CMV esophagitis (Fig. 5A and B). The 248 AGHA et al. Voi 81, No. 4, 1986 Fi(i. 1. Case 4. Endoscopic photograph of the esophagus shows several typical "volcano" ulcers {arrows) representing shallow uicers with a yellow rim due to herpetic esophagitis (HSV). diagnosis of herpes esophagitis was not considered in the six patients studied by conventional single contrast esophagrams. Pathological findings In six patients brush cytology was diagnostic of her- petic esophagitis. In one patient with concomitant HSV and Candida infection, viral cultures established the diagnosis. In three patients a definitive diagnosis of HSV esophagitis was made at postmortem examination (Fig. 6). Of the two patients with CMV esophagitis, FIG. 2. Case 1. Double contrast esophagram shows several small brush cytology was positive in one and the second discrete superficial ulcers due to HSV esophagitis. patient with acquired immunodeficiency syndrome was found to bave CMV esophagitis along with dissemi- nated CMV infection at autopsy. II (HSV-I and HSV-II), herpes zoster virus (HZV). Epstein-Barr virus, and CMV (12). Herpes simplex DISCUSSION virus and C. albicans infection in otherwise