^^T4 If > ' INTERNAL MEDICINE BOARD REVIEW DAVID L. LONGWORTH, MD, EDITOR JAMES K. STOLLER, MD, EDITOR

KAVITA R. KOLLURI, MD Dr. Kolluri is a fellow in the Cleveland Clinic Department of . Her special areas of interest include esophageal diseases and endoscopy.

DARWIN L. CONWELL, MD Dr. Conwell is an assistant staff member of the Cleveland Clinic Department of Gastroenterology. His special research interests include diseases of the pancreas and gastrointestinal endoscopy. A 34-year-old woman with odynophagia and weight loss

34-year-old woman came to the • Gastroesophageal reflux disease emergency department complaining • Oral of fever, chest pain, odynophagia • Peptic ulcer disease (pain on swallowing), and anorexia, • Idiopathic HIV-associated all lasting 1 week. She had passed esophageal ulcer A"dark" stools for 2 days and had lost 60 lh in • Cytomegalovirus the past 6 months. She denied any significant past medical history or surgeries. This young woman's history of polysubstance Her temperature was 38.3°C and blood abuse and weight loss makes human immun- pressure 95/64 mm Hg. A physical examina- odeficiency virus (HIV) infection a strong tion in the emergency department disclosed possibility. In fact, a serologic test for anti- nothing remarkable. An electrocardiogram II1V antibodies was positive in this patient. was normal. Her electrolyte levels were nor- Esophageal disease is common throughout mal, but her albumin level was 2.6 g/dL, the course of HIV infection: approximately hematocrit 30%, and mean corpuscular vol- 30% of HIV-positive patients acquire it.1 ume 87 fL. A plain roentgenogram of the Patients usually present with or abdomen was normal. odynophagia or both. The most common form The patient received intravenous fluids in is esophagitis due to infections with Candida; the observation unit and was scheduled for a other infecting organisms are cytomegalovirus gastroenterologic consultation as an outpa- and virus. tient. When seen in the gastroenterology clin- ic that week she still complained of odynopha- Ulcers produce more-severe symptoms gia but denied dysphagia. She said that she Cytomegalovirus and herpes simplex virus had to chew food very well to avoid "sticking." infections in the produce more- She admitted to abusing multiple substances, severe symptoms than do candidal infections including alcohol, tobacco, and "crack" because they cause ulcers, whereas Candida cocaine, but denied intravenous drug use or produces discrete plaques. Cytomegalovirus is sexual promiscuity. much more common than herpes simplex virus as a cause of HIV-associated esophageal WHAT IS THE DIAGNOSIS? ulcers.1 Medications can also cause esophageal On the basis of these findings, what is the ulcers in patients with HIV infection.2 Many 1 most likely diagnosis? patients with HIV infection take ulcerogenic

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FIGURE 1

SUGGESTED ALGORITHM FOR MANAGING ESOPHAGEAL SYMPTOMS IN PATIENTS WITH HIV INFECTION

Perform history and physical examination I 1 1 Possible drug-induced Characteristic gastroesophageal Odynophagia and dysphagia esophagitis reflux symptoms I i Discontinue drug Give histamine2 lild or moderate Severe or alter route blocker empirically of administration

Give fluconazole or ketoconazole empirically for 7-10 days

If no improvement

Perform endoscopy

From Wilcox, reference 3

medications such as zidovudine (AZT), zal- ble with peptic ulcers. citabine (ddC), and doxycycline. However, this patient does not take any medications. • WHAT IS THE NEXT STEP? Gastroesophageal reflux disease could cause esophageal ulcers in patients with HIV What is the next step in the care of this infection, but it is much less likely than in 2 patient? uninfected persons, because HIV infection • Barium swallow often causes gastric secretory failure and • Upper endoscopy hypochlorhydria.1 • Empiric medical therapy Idiopathic esophageal ulcers also occur in • Reassurance HIV disease, as has been recently reported.3 In fact, they may be second only to Because the most common cause of cytomegalovirus as a cause of esophageal dis- esophageal symptoms in patients with HIV ease in HIV-infected patients.1 Most idiopath- infection is candidal esophagitis,3 a patient ic ulcers are large. They most commonly afflict presenting with mild esophageal symptoms patients with advanced HIV disease, but can could be treated empirically with fluconazole. occur at any stage of the illness. If symptoms abate within 1 week, the diagno- This patient's symptoms are not compati- sis of candidal esophagitis can be made pre-

246 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 64 • NUMBER 5 MAY 1997 Downloaded from www.ccjm.org on September 25, 2021. For personal use only. All other uses require permission. sumptively; if the symptoms do not respond WHAT TREATMENT IS INDICATED? within 10 days, endoscopy is recommended to rule out other common causes of esophageal Which of the following is the appropriate symptoms (FIGURE 1). therapy for this patient? 3 • However, this patient has severe Prednisone odynophagia, dehydration, and weight loss. • Lansoprazole • Candidal infection does not usually cause • Ketoconazole such symptoms, but esophageal ulcers can. • Observation Esophageal ulcers are best diagnosed by Metoclopramide endoscopy; histopathologic and cytologic examination of the ulcer determines whether Corticosteroids are the treatment of choice for it has an infectious, or idiopathic cause. idiopathic esophageal ulcers. The exact mech- The patient therefore underwent anism of action of these drugs is unclear, but endoscopy, which revealed a 13-cm they are thought to blunt the inflammatory esophageal ulcer (FIGURE 2). Biopsy specimens process by affecting arachidonic acid metabo- of the ulcer showed inflammatory changes; lism through inhibition of phospholipase A2.4 specimens obtained by brushing were negative Wilcox and Schwartz5 recently compared for Candida, and no viral inclusions or malig- the outcomes of patients with HIV-associated nant cells were noted. A barium esophagram idiopathic esophageal ulcers who received also showed esophagitis and an ulcer approxi- prednisone for either 2 or 4 weeks. Of patients mately 12 to 13 cm long (FIGURES). who received the 2-week regimen, 52% expe- One could argue that treating rienced a relapse, compared with 22% who empirically with histamine2 receptor antago- received prednisone for 4 weeks; the differ- nists would be more cost-effective than per- ence was not statistically significant, due to forming endoscopy. However, as stated above, the small number of patients in the study gastroesophageal reflux disease infrequently (TABLE). The most common complications of causes ulcers in HIV-infected patients. treatment were cytomegalovirus infections,

FIGURE 2 FIGURE 3

FIGURE 2. Endoscopic view of the esophagus. Arrows mark the margin of the ulcer.

FIGURE 3. Barium esophagram. Arrows mark the top and bottom of the ulcer.

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TABLE cy, relapse rate, and complication rate is pred- PREDNISONE THERAPY nisone 40 mg daily, tapered over 4 weeks. FOR IDIOPATHIC H1V-RELATED Prednisone may not alter the mortality rate, ESOPHAGEAL ULCERS but it has shown to decrease the odynophagia, chest pain, and weight loss that occurs as a Variable 2 weeks 4 weeks result of this condition and thereby improve the quality of life, as it did in the case of our No. of patients 12 24 patient.

Response, N (%) 11 (92) 23 (96) Studies have shown a high rate of con- None 1 1 comitant Candida infections in patients with Partial 1 5 idiopathic esophageal ulcers and in patients Complete 10 18 who were treated with prednisone who had Relapse, N (%) 2(22) 12(52) relapsed.1 Therefore, it is prudent to give flu-

Median time to relapse, weeks 6 7 conazole as well. Ketoconazole, which requires an acidic gastric pH to be effective, has been Range of follow-up, months 1 to 30 1 to 28 reported to be less effective in patients with No. lost to follow-up 1 0 HIV, since as many as 50% are hypochlorhy- dric.3 We added fluconazole to our patient's

None of the differences were statistically significant regimen. From Wilcox, reference 5 A proton-pump inhibitor such as lanso- prazole or omeprazole, or a gastric motility drug such as metoclopramide, would not help unless the patient had gastroesophageal reflux GERD rarely Pneumocystis carinii pneumonia, Candida disease. causes esophagitis, and herpes simplex virus infec- A few patients do not respond to pred- esophageal tions. It is unclear whether cytomegalovirus nisone. Two case reports describe using ulcers in was missed on the original biopsy specimens or thalidomide in this situation with some suc- if the corticosteroid led to reactivation of cess; however, its side effects (peripheral neu- HIV-infected latent cytomegalovirus infection. There were ropathy and hypersensitivity) may preclude its patients no deaths. use in this patient population until larger stud- The optimal regimen that balances effica- ies are done.6-7 •

• REFERENCES 5. Wilcox CM, Schwartz DA. Comparison of two corticos- teroid regimens for the treatment of HIV-associated idio- 1. Wilcox CM, Schwartz DA, Clark WS. Esophageal ulcera- pathic esophageal ulcer. Am J Gastroenterol 1994; tion in human immunodeficiency virus infection. Causes, 89:2163-2167. response to therapy, and long-term outcome. Ann Intern 6. Ryan J, Colman J, Pedersen ]. Thalidomide to treat Med 1995; 123:143-149. esophageal ulcer in AIDS. N Engl J Med 1992; 2. Indorf AS, Pegram PS. Esophageal ulceration related to 327:208-209. zalcitabine (ddC), Ann Intern Med 1992; 117:133-134. 7. Naum SM, Molloy PJ, Kania RJ, McGarr J, Van Thiel 3. Wilcox CM. Esophageal disease in the acquired immun- DH. Use of thalidomide in treatment and maintenance of odeficiency syndrome: etiology, diagnosis, and manage- idiopathic esophageal ulcers in HIV+ individuals. Dig Dis ment. Am J Med 1992; 92:412-421. Sci 1995;40:1147-1148. 4. Kotler DP, Reka S, Orenstein JM, Fox CH. Chronic idio- pathic esophageal ulceration in the acquired immunodefi- ADDRESS RERINT REQUESTS to Kavita R. Kolluri, MD, ciency syndrome. Characterization and treatment with Department of Gastroenterology, S40, The Cleveland Clinic corticosteroids. J Clin Gastroenterol 1992; 15:284-290. Foundation, 9500 Euclid Avenue, Cleveland, OH 44195.

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