A 34-year-old woman with odynophagia and weight loss

^ ^ T 4 I f > '

DAVID L. LONGWORTH, MD, EDITOR JAMES K. STOLLER, MD, EDITOR

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

DARWIN L. CONWELL, M D Dr. Conwell is an assistant staff member of the Cleveland Clinic Department of Gastroenterology. His special research interests include diseases of the pancreas and gastrointest inal endoscopy.

INTERNAL MEDICINE BOARD REVIEW

A 34-year-old woman with odynophagia and weight loss

A34-year-old woman came to the emergency department complaining of fever, chest pain, odynophagia (pain on swallowing), and anorexia, all lasting 1 week. She had passed

"dark" stools for 2 days and had lost 60 lh in the past 6 months. She denied any significant past medical history or surgeries.

Her temperature was 38.3°C and blood pressure 95/64 mm Hg. A physical examina-tion in the emergency department disclosed nothing remarkable. An electrocardiogram was normal. Her electrolyte levels were nor-mal, but her albumin level was 2.6 g/dL, hematocrit 30%, and mean corpuscular vol-ume 87 fL. A plain roentgenogram of the abdomen was normal.

The patient received intravenous fluids in the observation unit and was scheduled for a gastroenterologic consultation as an outpa-tient. When seen in the gastroenterology clin-ic that week she still complained of odynopha-gia but denied dysphagia. She said that she had to chew food very well to avoid "sticking." She admitted to abusing multiple substances, including alcohol, tobacco, and "crack" cocaine, but denied intravenous drug use or sexual promiscuity.

1

WHAT IS THE DIAGNOSIS?

On the basis of these findings, what is the most likely diagnosis?

• Gastroesophageal reflux disease • Oral candidiasis • Peptic ulcer disease • Idiopathic HIV-associated

esophageal ulcer • Cytomegalovirus esophagitis

This young woman's history of polysubstance abuse and weight loss makes human immun-odeficiency virus (HIV) infection a strong possibility. In fact, a serologic test for anti-II1V antibodies was positive in this patient.

Esophageal disease is common throughout the course of HIV infection: approximately 30% of HIV-positive patients acquire it.1

Patients usually present with dysphagia or odynophagia or both. The most common form is esophagitis due to infections with Candida; other infecting organisms are cytomegalovirus and herpes simplex virus.

Ulcers produce more-severe symptoms Cytomegalovirus and herpes simplex virus infections in the esophagus produce more-severe symptoms than do candidal infections because they cause ulcers, whereas Candida produces discrete plaques. Cytomegalovirus is much more common than herpes simplex virus as a cause of HIV-associated esophageal ulcers.1

Medications can also cause esophageal ulcers in patients with HIV infection.2 Many patients with HIV infection take ulcerogenic

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ODYNOPHAGIA I KOLLURI AND CONWELL

F I G U R E 1

SUGGESTED A L G O R I T H M FOR M A N A G I N G ESOPHAGEAL S Y M P T O M S IN PATIENTS W I T H HIV INFECT ION

Per fo rm h is to ry a n d phys ica l e x a m i n a t i o n

I Possible d r u g - i n d u c e d

esophag i t i s

I Discon t i nue d r u g

or a l ter r ou te o f a d m i n i s t r a t i o n

1 Charac te r i s t i c g a s t r o e s o p h a g e a l

re f lux s y m p t o m s

i Give h i s tam ine 2

b locker emp i r i ca l l y

1 O d y n o p h a g i a a n d d y s p h a g i a

l i l d or m o d e r a t e Severe

G ive f l u c o n a z o l e o r k e t o c o n a z o l e

emp i r i ca l l y fo r 7 - 1 0 days

If no i m p r o v e m e n t

Per form e n d o s c o p y

From Wilcox, reference 3

medications such as zidovudine (AZT) , zal-citabine (ddC), and doxycycline. However, this patient does not take any medications.

Gastroesophageal reflux disease could cause esophageal ulcers in patients with HIV infection, but it is much less likely than in uninfected persons, because HIV infection often causes gastric secretory failure and hypochlorhydria.1

Idiopathic esophageal ulcers also occur in HIV disease, as has been recently reported.3 In fact, they may be second only to cytomegalovirus as a cause of esophageal dis-ease in HIV-infected patients.1 Most idiopath-ic ulcers are large. They most commonly afflict patients with advanced HIV disease, but can occur at any stage of the illness.

This patient's symptoms are not compati-

ble with peptic ulcers.

• WHAT IS THE NEXT STEP?

2What is the next step in the care of this patient? • Barium swallow • Upper endoscopy • Empiric medical therapy • Reassurance

Because the most common cause of esophageal symptoms in patients with HIV infection is candidal esophagitis,3 a patient presenting with mild esophageal symptoms could be treated empirically with fluconazole. If symptoms abate within 1 week, the diagno-sis of candidal esophagitis can be made pre-

2 4 6 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 6 4 • NUMBER 5 M A Y 1997



sumptively; if the symptoms do not respond within 10 days, endoscopy is recommended to rule out other common causes of esophageal s y m p t o m s (FIGURE 1 ) .

However, this patient has severe odynophagia, dehydration, and weight loss. Candidal infection does not usually cause such symptoms, but esophageal ulcers can. Esophageal ulcers are best diagnosed by endoscopy; histopathologic and cytologic examination of the ulcer determines whether it has an infectious, or idiopathic cause.

T h e patient therefore underwent endoscopy, which revealed a 13-cm esophageal ulcer (FIGURE 2). Biopsy specimens of the ulcer showed inflammatory changes; specimens obtained by brushing were negative for Candida, and no viral inclusions or malig-nant cells were noted. A barium esophagram also showed esophagitis and an ulcer approxi-mately 12 to 13 cm long (FIGURES).

One could argue that treating heartburn empirically with histamine2 receptor antago-nists would be more cost-effective than per-forming endoscopy. However, as stated above, gastroesophageal reflux disease infrequently causes ulcers in HIV-infected patients.

3 WHAT TREATMENT IS INDICATED?

Which of the following is the appropriate therapy for this patient? •

• • • •

Prednisone Lansoprazole Ketoconazole Observation Metoclopramide

Corticosteroids are the treatment of choice for idiopathic esophageal ulcers. The exact mech-anism of action of these drugs is unclear, but they are thought to blunt the inflammatory process by affecting arachidonic acid metabo-lism through inhibition of phospholipase A2.4

Wilcox and Schwartz5 recently compared the outcomes of patients with HIV-associated idiopathic esophageal ulcers who received prednisone for either 2 or 4 weeks. Of patients who received the 2-week regimen, 52% expe-rienced a relapse, compared with 2 2 % who received prednisone for 4 weeks; the differ-ence was not statistically significant, due to the small number of patients in the study (TABLE). The most common complications of treatment were cytomegalovirus infections,

F I G U R E 3

FIGURE 2. Endoscop i c v i e w o f t h e e s o p h a g u s . A r r o w s m a r k t h e m a r g i n o f t h e ulcer.

FIGURE 3. B a r i u m e s o p h a g r a m . A r r o w s m a r k t h e t o p a n d b o t t o m o f t h e ulcer.

CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 6 4 • NUMBER 5 M A Y 1997 2 2 9

F I G U R E 2



ODYNOPHAGIA • KOLLURI AND CONWELL

T A B L E

GERD rarely causes esophageal ulcers in HIV-infected patients

PREDNISONE THERAPY FOR IDIOPATHIC H1V-RELATED

ESOPHAGEAL ULCERS

V a r i a b l e 2 w e e k s 4 w e e k s

No . o f p a t i e n t s 12 2 4

Response , N ( % ) 11 ( 9 2 ) 2 3 ( 9 6 ) N o n e 1 1 Par t ia l 1 5 C o m p l e t e 1 0 18

Relapse, N ( % ) 2 ( 2 2 ) 1 2 ( 5 2 )

M e d i a n t i m e t o re lapse , w e e k s 6 7

R a n g e of f o l l o w - u p , m o n t h s 1 t o 3 0 1 t o 2 8

No. l os t t o f o l l o w - u p 1 0

N o n e o f t h e d i f f e r e n c e s w e r e s t a t i s t i c a l l y s i g n i f i c a n t F rom W i l c o x , r e f e r e n c e 5

Pneumocystis carinii pneumonia, Candida esophagitis, and herpes simplex virus infec-tions. It is unclear whether cytomegalovirus was missed on the original biopsy specimens or if the corticosteroid led to reactivation of latent cytomegalovirus infection. There were no deaths.

The optimal regimen that balances effica-

cy, relapse rate, and complication rate is pred-nisone 40 mg daily, tapered over 4 weeks. Prednisone may not alter the mortality rate, but it has shown to decrease the odynophagia, chest pain, and weight loss that occurs as a result of this condition and thereby improve the quality of life, as it did in the case of our patient.

Studies have shown a high rate of con-comitant Candida infections in patients with idiopathic esophageal ulcers and in patients who were treated with prednisone who had relapsed.1 Therefore, it is prudent to give flu-conazole as well. Ketoconazole, which requires an acidic gastric pH to be effective, has been reported to be less effective in patients with HIV, since as many as 5 0 % are hypochlorhy-dric.3 We added fluconazole to our patient's regimen.

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 disease.

A few patients do not respond to pred-nisone. Two case reports describe using thalidomide in this situation with some suc-cess; however, its side effects (peripheral neu-ropathy and hypersensitivity) may preclude its use in this patient population until larger stud-ies are done.6-7 •

• REFERENCES 1. Wilcox C M , Schwartz DA, Clark W S . Esophageal ulcera-

tion in human immunodeficiency virus infection. Causes, response to therapy, and long-term outcome. A n n Intern Med 1995; 1 2 3 : 1 4 3 - 1 4 9 .

2. Indorf A S , Pegram PS. Esophageal ulceration related to zalcitabine (ddC), A n n Intern Med 1992; 1 1 7 : 1 3 3 - 1 3 4 .

3 . Wilcox C M . Esophageal disease in the acquired immun-odeficiency syndrome: etiology, diagnosis, and manage-ment. A m J Med 1992; 9 2 : 4 1 2 - 4 2 1 .

4. Kotler DP, Reka S, Orenstein JM, Fox C H . Chronic idio-pathic esophageal ulceration in the acquired immunodefi-ciency syndrome. Characterization and treatment with corticosteroids. J Cl in Gastroenterol 1992; 1 5 : 2 8 4 - 2 9 0 .

2 4 8 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 64 • NUMBER 5 M A Y 1997

5. Wi lcox C M , Schwartz DA. Comparison of two corticos-teroid regimens for the treatment of HIV-associated idio-pathic esophageal ulcer. A m J Gastroenterol 1994; 8 9 : 2 1 6 3 - 2 1 6 7 .

6. Ryan J, Co lman J, Pedersen ]. Thal idomide to treat esophageal ulcer in A I D S . N Engl J Med 1992; 3 2 7 : 2 0 8 - 2 0 9 .

7. Naum S M , Molloy PJ, Kania RJ , M c G a r r J , Van Thie l DH. Use of thalidomide in treatment and maintenance of idiopathic esophageal ulcers in H I V + individuals. Dig Dis Sc i 1 9 9 5 ; 4 0 : 1 1 4 7 - 1 1 4 8 .

ADDRESS RERINT REQUESTS t o K a v i t a R. K o l l u r i , M D , D e p a r t m e n t o f G a s t r o e n t e r o l o g y , S40, T h e C l e v e l a n d Cl in ic F o u n d a t i o n , 9500 Eucl id A v e n u e , C leve land , O H 44195 .



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A 34-year-old woman with odynophagia and weight loss