Esophageal candidiasis

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Gastroenterologia Japonica Copyright 9 1988 by The Japanese Society of Gastroenterology

Vol. 23, No. 4 Printed in Japan

--Original Article--

Esophageal candidiasis Yuji NAITO, Toshikazu YOSHIKAWA, Hirokazu OYAMADA, Kenzo TAINAKA, Yutaka MORITA, Takafumi KOGAWA, Shigeru SUGINO and Motoharu KONDO

First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kyoto 602, Japan Summary: Among 3,501 individuals receiving endoscopic examination for the upper digestive tract, 41 were found to have esophageal candidiasis including 17 malignancies, 14 immunological disorders, 4 diabetes mellitus, 7 other underlying diseases and 7 apparently healthy sujbects. The diagnosis was made either by brushing of the esophagus or by histological examination of the biopsied specimen. Systemic invasion of fungi was observed mainly in patients with malignancy invloving the hematopoietic system, and most of them had been treated by corticosteroids, antibiotics or anticancer agents. Although complications associated with esophageal condidiasis are rare, it is emphasized that those patients with malignancy as well as impared immunity should be carefully examined for esophageal candidiasis, in order to prevent the fungi from developing invasive candidiasis. It should be noted that a few cases of gastric ulcer treated by H2 blocker revealed esophageal candidiasis, suggesting that decrease of gastric acidity might be one of the factors involved in this pathological condition.

Gastroenterol Jpn 1988;23:363-370 Key Words:

Endoscopy, Esophageal candidiasis, Invasive candidiasis

Introduction

Esophageal candidiasis is m o r e p r e v a l e n t t h a n previously r e c o g n i z e d 1-4. It is m o s t often f o u n d in patients w i t h i m p a i r e d i m m u n e f u n c t i o n and also in a p p a r e n t l y n o r m a l i n d i v i d u a l s 5. Although Candida albicans is the m o s t c o m m o n causative o r g a n i s m , other species, i n c l u d i n g Candida krusei, Candida tropicalis a n d Candida stellatoidea, have occasionally b e e n isolated 6. The classic r o e n t g e n o g r a p h i c picture of this disease is that of a s h a g g y m u c o s a l surface w i t h a saw-tooth or c o b b l e s t o n e a p p e a r a n c e reflecting mucosal ulceration, a g g r e g a t i o n of fungi, or inflammatory e x u d a t e 7. O n the o t h e r h a n d , a substantial n u m b e r of patients, especially those with mild infection, s h o w no radiologic abnormalitys. Recent advances in e n d o s c o p y h a v e resulted

in f r e q u e n t a n d easy d e m o n s t r a t i o n of e s o p h a geal candidiasis 1'2. The m u c o s a is usually c o v e r e d w i t h w h i t e plaque-like lesions that overlie a friable, e r y t h e m a t o u s m u c o s a , w i t h or w i t h o u t associated superficial ulceration. In a p r o s p e c t i v e s t u d y of 370 p a t i e n t s w h o u n d e r w e n t e s o p h a g o s c o p y , Kodsi f o u n d 27 p a t i e n t s w i t h e s o p h a g e a l c a n d i d i a s i s 2. H o w e v e r , the d e m o n s t r a t i o n of c a n d i d a in cultures, w h i c h is the criterion for the d i a g n o s i s p r o p o s e d by Kodsi et al., is n o t reliable e v i d e n c e for e s o p h a g e a l candidiasis, b e c a u s e this o r g a n i s m is a c o m m o n c o m m e n s a l a n d its p r e s e n c e does n o t i m p l y a pathological state. The d i a g n o s i s m u s t be e s t a b l i s h e d b y d e t e c t i n g characteristic e n d o s c o p i c a p p e a r a n c e s a n d v i s u a l i z i n g the yeast or mycelial forms in e n d o s c o p i c b r u s h i n g or b i o p s y s p e c i m e n s 8. We e x a m i n e d the clinical features of e s o p h -

Received November 30, 1987. Accepted February 8, 1988. Address for correspondence: Yuji Naito, M.D., First Department of Internal Medicine, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602, Japan.

364

Y. Naito et al.

Fig. 1 Endoscopic classification of esophageal candidiasis according to Kodsi's grading system Grade I : a few raised white plaques with hyperemia but no edema or ulceration Grade II : characteristic multiple white plaques with hyperemia and edema but no ulceration Grade II1: confluent, linear and nodular elevated plaques with hyperemia and frank ulceration Grade IV: the same findings as grade III plus increased friability of the membrane and occasional narrowing of the lumen

ageal candidiasis, and evaluated the usefulness of endoscopic examination for the diagnosis and follow-up study of this disease. Materials and Methods D u r i n g a period of 6 years, a total of 3,501 patients w e r e e x a m i n e d by u p p e r gastrointestinal panendoscopy. Diagnosis of esophageal candidiasis was m a d e by the characteristic endoscopic findings, and each case was verified by the fungal mycelia o b t a i n e d by direct brushing smear or by mucosal biopsy specimens. Culture of specimens for candida was not d o n e routinely. These cases w e r e classified endoscopically according to Kodsi's grading system 2. Grade I shows a few raised w h i t e plaques w i t h hyperemia but no e d e m a or ulceration. Grade II has characteristic multiple white plaques w i t h hyperemia and e d e m a but no ulceration, whereas

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grade III has confluent, linear and nodular elevated plaques w i t h h y p e r e m i a and flank ulceration. Grade IV shows the same findings as grade III plus increased friability of the membrane and occasional n a r r o w i n g of the lumen (Fig. 1). The relationship of grade w i t h subjective symptoms, location of the lesion, accomp a n y i n g lesion, laboratory examination, and therapeutic efficacy w e r e investigated. In all patients w h i t e blood cell and neutrophil count w e r e m e a s u r e d at the onset of candidiasis and at irregular intervals. 18 patients were exa m i n e d by tuberculin skin test, using a solution containing the equivalent of 5 tuberculin units of purified protein derivative. The reaction was e x a m i n e d 48 h later and was considered positive if the d i a m e t e r of the area of redness measu r e d 10 m m or more, doubtful if it was 5 to 10 m m , and negative if it was less than 5 mm. Results

Number of the patients with esophageal candidiasis A m o n g 3,501 patients examined, 41 cases (1.2%) w e r e d i a g n o s e d as h a v i n g esophageal candidiasis.

Age and Sex The average age of the patients was 49.9 years ranging from 16 to 82 years. There w e r e 22 men and 19 w o m e n .

Underlying illness These 41 cases included 17 cases of malignancy (6 acute leukemia, 5 carcinoma, 2 multiple myeloma, 2 myelodysplastic syndrome, 1 i m m u n o b l a s t i c l y m p h a d e n o p a t h y and 1 malignant thymoma), 14 immunological disorders m a i n l y a u t o i m m u n e diseases, 4 diabetes mellitus, 7 other u n d e r l y i n g diseases, and 7 cases w i t h o u t a p r e d i s p o s i n g condition including a patient a d m i n i s t e r e d c i m e t i d i n e due to gastric ulcer and three patients w h o h a d undergone subtotal gastrectomy.

Predisposing drugs The 41 cases also i n c l u d e d 25 patinets (61%)

Esophageal candidiasis

August 1988

Table 1 Subjective symptoms of the esophageal candidiasis and

relation between the endoscopic grading according to Kodsi's criteria and subjective symptoms Dysphagia Odynophagia Nausea Sore throat Epigastralgia Hert burn

4 4 4 3 3 1

Total

19 symptoms/13 cases (32%)

Kodsi's grade

Positive subjective symptoms

Grade I

0/9 (

0%)

Grade Jl

7/16 ( 4 4 % )

Grade III

5/15 ( 3 3 % )

Grade IV

1/1 (100%)

having been treated by corticosteroids, 12 (29%) by antibiotics and 10 (24%) by anticancer drugs.

Endoscopic grading according to Kodsi's criteria and diagnosis Nine cases were classified as grade I, 16 as grade II, 15 as grade III and one as grade IV. Thirty nine cases (95%) were detected at the first endoscopic examination. The incidence of positive demonstration of candida mycelia was 100% by direct brushing smear and 46% by biopsy. In biopsy specimens, the incidence of positive demonstration of candida increased in parallel with Kodsi's criteria: 22% in grade I, 36% in II, 67% in III, 100% in IV. However, candidiasis could be detected in only 9 of the 24 cases examined by double contrast esophagography.

Subjective symptoms Only 13 patients (32%) had subjective symptoms attributable to esophageal candidiasis, such as dysphagia, odynophagia and nausea (Table 1). Nine cases of grade I patients had no subjective symptoms. Therefore it is difficult to detect this disease in its early stage only by subjective symptoms.

365

Table 2 Upper gastrointestinal lesions accompanied esophageal candidiasis and 20 cases of the esophageal candidiasis with erosive or ulcerative lesions Esophagus Diverticulum Hiatal hernia Carcinoma Barrett's esophagus

2 2 2 1

Stomach Erosive gastritis Ulcer Postgastrectomy Xanthoma Carcinoma AGML Giant rugae Subrnucosal tumore Hyperplastic polyp

15 6 4 3 1 1 1 1 1

Total

40 lesions/29 cases (71%)

Kodsi's grade

Number of cases (%)

Grade I

5/9 ( 5 6 % )

Grade II

7/16 ( 4 4 % )

Grade III

8/15 ( 5 3 % )

Grade IV

0/1 ( 0 % )

Total

20/41 ( 4 9 % )

AGML: acute gastric mucosal lesion

Location of the lesion Fungi in the esophagus were present in the lower portion in 9 (23%), in the m i d d l e to lower esophagus in 16 (39%) and in all parts of the esophagus in 13 respectively (32%).

Upper gastrointestinal esophageal candidiasis

lesions

accompanying

Twenty nine cases (71%) were accompanied by upper gastrointestinal findings, mainly erosive or ulcerative lesions of the stomach (Table 2). There was no correlation between gastric ulcerative lesions and endoscopic grading according to Kodsi's criteria.

Neutrophil count and tuberculin skin test There was no correlation between endoscopic grading and neutrophil count, however, in the patients w h o died of invasive candidiasis, neutrophil counts were less than 1,000~;

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Y. Naito et al.

Table 3 Relation between endoscopic grading according to Kodsi's criteria and tuberculin skin test Kodsi's grade

PPD skin test

(-), (_+)

(+)

Grade I

0

2

Grade II

6

3

Grade III

4

2

Grade IV

1

0

(-): negative (+): doubtfull (+): positive

(18 cases)

cram. Tuberculin skin test was performed as an index of the cellular immunological state of the patient. The incidence of negative and doubtful skin test was 0% in grade I, 67% in grade II, 67% in grade III and 100% in grade IV respectively (Table 3).

Treatment and efficacy Thirty patients w e r e treated w i t h anti-fungal agents such as amphotericin B (Squibb Japan INC. Tokyo), nystatin (Meiji, Tokyo) and ketoconazole. Table 4 shows the the initial treatment and its efficacy. White plaques disappeared w i t h i n 4 weeks in 21 patients, the n u m ber and size of the white plaques d i m i n i s h e d in 3 patients and treatment was ineffective in 7 patients. Table 5 shows the 7 patients w h o did not respond to the initial treatment. In Case 2, the white plaque lesions disappeared after the change of medication from amphotericin B tablet to syrup. In the 5 cases in w h i c h the predisposing disease was malignancy of the hematopoietic system, the neutrophil counts markedly decreased and 4 patients died of systemic invasion of fungi. Eight patients w e r e treated w i t h a single daily tablet of 200 mg ketoconazole (Table 6). Endoscopic examination was performed 2 weeks later and 6 patients s h o w e d m a r k e d improvements. In Case 6 (Table 6), the lesion of the esophagus s h o w e d little i m p r o v e m e n t even after the treatment for 4 weeks. In Case 7 (Table 6), the patient died of invasive candidiasis despite continuous treatment w i t h

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Table 4 Efficacy of the anti-fungal agents for the initial treatment of esophageal candidiasis Drug AmphotericinB Efficacy S y r u p Tablet I,V. Markedly Effective

10/19

Effective

3/19

Ineffective

6/19

1/1

1/1

NystatinKetoconazole Rate of Syrup Tablet Efficacy 4/4

6/6

24/31 (77%) 7/31 (23%)

I.V.: intravenous administration

ketoconazole. Table 7 shows predisposing factors and clinical course in 8 cases of invasive candidiasis. In all cases, cellular i m m u n i t y of the host was severely i m p a i r e d by the u n d e r l y i n g malignancy of the hematopoietic system or by imm u n o s u p p r e s s i v e therapy. In Case 8 (Table 7), however, the patient was successfully treated w i t h intravenous A m p h o t e r i c i n B, because the early stage of esophageal candidiasis could be detected by the endoscopic findings.

Local complication As local complications of this disease, we experienced 3 cases of esophageal hemorrhage, 2 cases of mucosal bridge formation, 1 case of stricture formation and 1 case of perforation. Discussion

Esophageal candidiasis was considered to be rare and to occur mainly in debilitated or imm u n o s u p p r e s s e d patients 1"4. H o w e v e r , we found a h i g h incidence of this disease among patients u n d e r g o i n g u p p e r gastrointestinal endoscopy. The incidence of the esophageal candidiasis in our report is 1.2%, w h i c h was less than the incidence reported by Kodsi of 8% 2, probably due to our more strict diagnostic criteria. In the present study, 34 patients had an u n d e r l y i n g illness, but 7 w e r e apparently healthy persons. It is importatnt to recognize that esophagreal candidiasis can occur in apparently normal individuals. PhaosawasdP speculated that decreased gastric acid output is

Esophageal candidiasis

August 1988

Table

5 Seven cases of the esophageal candidiasis with ineffectual initial treatment Case

r

367

Predisposing

!No. Age, Sex

Disease

Drugs

Neutrophil Antitumor Count Steroid Antibiotics drug /mm 3

Clinical course under Endoscopy 2w 4w 2M 4M 6M

0

AS IBL

+

+

-

1100

11

55, M

AGA

+

-

--

8040

[ll

3

39, M

AML

+

+

+

12

II

4

54,

F

Multiple Myeloma

+

--

+

1730

5

37,

F

AML

+

+

+

0

6

71, M

MDS

-

+

-

620

7

55, M

unremarkable

-

--

-

1540

1

49,

2

F

Result of Esophageal Candidiasis

IC (death)

9 Ic AT

AS - II

0

AS AD

AS

Disappear ( A T - AS)

IC

IC (death)

died of

ll--II~

multiple myeloma

AS l~lC

No change until death

IC (death) AS

[

IC

IC (death)

AS Ill--Ill

No change

IBL: immunoblastic lymphadenopathy, AGA: allergic granulomatous a r t e r i t i s , A M L : acute myeloid leukemia, MDS : myelodysplastic syndrome, AS : amphotericin B syrup, AT: amphotericin B tablet, AD: drip infusion of amphotericin B, IC: invasive candidiasis, l,ll,lll: Kodsi's grade, 0: disappearance of candidiasis

Table

6 Ketoconazole treatment of the esophageal candidiasis Case

No. Age, Sex

Predisposing disease

(Dose : 200 rngJday)

Clinical course under Endoscopy 0

2

4 I

8 I

12

16 weeks I

Adrn.inistrat=on

Total dose

(Day)

(g)

Duration of candidiasis (Day)

1

56, F

SLE

I1 K'r 0

12

2.4

12

2

49,

RA, DM Drug eruption

I KT 0

13

2.6

13

3

56 , M

Gastric cancer (Brain meta)

l

KT 90

17

3.4

17

4

42 , F

MDS

11,

AS ; I KT 0 K--~T0

66

13.2

26

5

51 , M Multiple myeloma

11

AS

, I KT 0

15

3.0

15

6

55, M

Pulmonary Tbc.

II

KT

- I KT 0

76

15.2

57

7

33

ALL .

45

9.0

20

14

2-8

14

32.3

6.5

21.8

8

F

.

M

30 , F

.

Toxic e p i d e r m o l y t i c

necrolysis

Drug induced hepatitis

.

II~TI K T o K T [l

Free Free

0 I

Invasive candidiasis

0 Mean

i

F: female, M: male, SLE: systemic lupus erythematosus, RA: rheumatoid a r t h r i t i s , DM: diabetes mellitus, M D S : myelodysplastic syndrome, Tbc.: tuberculosis, ALL: acute lymphoid leukemia, KT: ketoconazole tablet, AS: amphotericin B syrup, F r e e : s t a t u s of drug free, [,H,[II: Kodsi's grade, 0: disappearance of candidiasis

side effect

368

Table

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Y. Naito et al.

7 Eight cases of the invasive candidiasis Case

Predisposing

No. Age, Sex Disease

Drugs Steroid

Antibiotics

Neut rophil Count

Clinical course under Endoscopy Antitumor drug

1

37.

F

AML

+

+

+

2

49,

F

IBLA

+

+

-

3

24,

F

A M L , SLE

+

+

+

4

71,

M

MDS

-

+

+

5

39,

M

AML

+

+

+

6

33,

M

ALL

+

+

+

7

52,

M

AML

+

-

+

8

16,

M

AML

+

+

+

0

2w 4w

I

I

2M 4M 6M 1u

I

I

I

I

I

2Y

3Y

I

I

/ m m :~

(just before de~th)

AS 1

0

ic

9

AS 1[

90

9 IC

AS

AS

Ill--0

0

9 ic AS

I

-

AS 11 AS

2050

IC

-

AD 9 Ic

AS AS

0 AS AS

ll--[I]-- [l~[]]-AS

AS

AS

1--11--0

AD IV

-

AD . ~0

O~ 0

AS

KT MD

-lfl--O-IC

AS AS

2000 0

m--o--it

MD 0~lC

2O

F: female, M: male, A M L : acute myeloid Leukemia, I BL: immunoblastic lymphadenopathy, SLE : systemic lupus erythematosus, MDS : myelodysplastio syndrome, ALL : acute lymphoid leukemia, AS: amphotericin B syrup, KT: ketoconazole tablet, MD: drip infusion of miconazole, AD: drip infusion of amphotericin B, l,II,lll,~: Kodsi's grade, 0: disappearance of candidissis, IC: invasive candidiasis

one of the major factors in candidiasis infection and cautioned against prolonged treatment with cimetidine. Panendoscopy of the upper gastrointestinal tract is the key to the diagnosis of esophageal candidiasis 1-4. The mucosa is usually covered with white plaque-like lesions, aggregation of fungi and inflammatory exudate that overlie a friable, erythematous mucosa. The diagnosis can usually be established by visualizing yeast and/or mycelial forms in direct brushings of the lesionsz'8. Kodsi 2 found that the direct smear from the plaques was consistently positive for candida, whereas the direct smear from reflux esophagitis was consistently negative. We demonstrated mycelial tissue invasion in specimens obtained by endoscopic biopsy in 46% of the cases. Thus endoscopic biopsy appears to be less sensitive for establishing the diagnosis than examination of superficial brushing specimens of the lesions. However, biopsy is necessary for all cases in which the

possibility of esophageal malignancy has been raised and may be helpful in distinguishing candida from herpetic esophagitis9. Histologically herpetic esophagitis is recognized by the presence of eosinophilic intranuclear inclusions in epithelial cells8. Detection of a white plaque-like lesion by endoscopy is the first step in the diagnosis of this disease, especially in cases with grade I or II esophagitis in which roentgenographic examination is not particularly effective. Additionally, routine panendoscopic examination should be performed in immunocompromised hosts with or without subjective symptoms, for the early detection of candida esophagitis. The polyene antibiotics, nystatin and amphotericin B, are first choice drugs for the treatment of esophageal candidiasis and are administered in a methylcellulose suspension three or four times daily. Patients with malignancy of the hematopoietic system may not respond to oral use of nystatin or amphotericin B syrup 8.

August 1988

Esophageal candidiasis

Invasive candidiasis initiating from the gastrointestinal tract often results in death because of systemic infection 1~ In all our cases, the cellular i m m u n i t y of the host was severely i m p a r e d by the u n d e r l y i n g malignancy of the hematopoietic system or by immunosuppressive therapy. In such patients, candida esophagitis d e m o n s t r a t e d by endoscopic examination, should be treated with intravenous amphotericin B or miconazole, because clinical features, blood cultures, and serological tests are usually of no assistance in establishing the diagnosis early in the course of the infection 11"12. Miconazole, an imidazole derivative, is k n o w n to b i n d m e m b r a n e sterols and inhibit sterol synthesis in fungi, cause cell membrance damage, and also inhibits the uptake of nucleic acid precursors. Nausea, vomiting and central nervous system toxicity are the most common side effects of miconazole. Treatment of this disorder w i t h ketoconazole, a relatively n e w imidazole derivative, has been reported to resolve esophageal candidiasis w i t h i n 8 days in patients in an i m m u n o d e f i c i e n t state 13. In this prospective study, 7 out of 8 patients responded to ketoconazole w i t h i n 4 weeks, including two cases in w h i c h efficacy was not prominent. In a patient with malignancy of the hematopoietic system, oral administration of ketoconazole did not prevent the d e v e l o p m e n t of invasive candidiasis. Tavitian 14reported that in patients with acquired i m m u n o d e f i c i e n c y syndrome esophageal candidiasis m i g h t not be resolved even with 6 m o n t h s of ketoconazole therapy, and suggested that it m i g h t require more vigorous antifungal therapy than in patients in other states of immunodeficiency. Ketoconazole, at a daily dose of 200 mg, was found to be safe w i t h no side effects in all cases. As reported by Lewis 15, clinical hepatitis is quite rare and appears to develop in elderly women w h o have had reactions to other antifungal drugs. Although complications associated with esophageal candidiasis are very rare, delay in the diagnosis may result in esophageal steno-

369

sis, fistula formatin, perforatin and invasive candidiasis 16-18. To our k n o w l e d g e , this is the first report of cases of mucosal briding of the e s o p h a g u s secondary to candidiasis. In conclusion, we e m p h a s i z e that these patients w i t h malignancy, especially of the hematopoietic system, should routinely receive routine endoscopic examination, and, if candida esophagitis is d e m o n s t r a t e d by endoscopy, intravenous antifungal agents, a m p h o tericine B or miconazole, should be given. In those patients w i t h or w i t h o u t other predisposing diseases, the oral use of a m p h o t e r i c i n e B syrup, miconazole syrup and ketoconazole tablets m a y also be effective. References 1. Natio Y, Kogawa T, Tainaka K, et al: Analysis of 25 cases of esophageal moniliasis. Progress of Digestive Endoscopy 1985;26:63-68 2. Kodsi BE, Wickrernesinghe PC, Kozinn PJ, et ah Candida esophagitis. A prospective study of 27 cases. Gastroenterology 1976;71:715-719 3. Scott BB, Jenkins D: Gastro-oesophageal candidiasis. Gut 1982;23:137-139 4. Trier J, Bjorkrnan DJ: Esophageal, gastric and intestinal candidiasis. Candidiasis; A growing concern. Am J Med 1984;77(4D):39-43 5. Phasowasdi K, Rice P, Lee B: Primary and secondary candida esophagitis in normal, healthy subjects. Illinois Med J 1986;169:361-365 6. Smith JMD: Mycosis of the alimentary tract, progress report. Gut 1969;10:1035-1040 7. Guyer PB, Brunton FJ: Candidiasis of the oeophagus. Br J Radiol 1971;44:131-136 8. Mathieson R, Dutta SK: Candida esophagitis. Dig Dis Sci 1983;28:365-370 9. Levine MS, Laufer I, Kressel HY, et al: Herpes esophagitis. AJR 1981;136:863-866 10. Maksyrnivk AW, Thongprasert S, Hopfer R, et al: Systemic candidiasis in cancer patients. Candidiasis; A growing concern. Am J Med 1984;77(4D):20-27 11. Kozzin P, Taschdjian M, Goldberg P, et al: Efficiency of serologic tests in the disgnosis of systemic candidiasis. Am JClin Pathol 1978;70:893-898 12. Meunier-carpentier F, Armstrong D: Candida antigenernia, as detected by passive hernagglutination inhibition, in patients with disseminated candidiasis or candida colonization. J Clin Microbiol 1981;13:10-14 13. Fazio RA, Wickrernesinghe PC, Arsura EL: Ketoconazole treatment of candida esophagitis - A prospective study of 12 cases. Am J Gastroenterol 1983;78:261-264 14. Tabitian A, Raufrnan JP, Rosenthal LE, et al: Ketoconazoleresistent candida esophagitis in patients with Acquired

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Immunodeficiency Syndrome. Gastroenterology 1986;90:443445 15. Lewis JH, Zimmerrnan HJ, Benson GD, et al: Hepatic injury associated with ketoconazole therapy. Analysis of 33 cases. Gastroenterology 1984;86:503-513 16. Kelvin F, Clark W, Thompson W, et al: Chronic esophageal stricture due to moniliasis. Br J Radiol 1978;51:826-828

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17. Jones JM: Necrotizing candida esophagitis. Failure of symptoms and roentgenographic findings to reflect severity. JAMA 1980;244:2190-2191 18. Obrecht WF, Richter JE, et al: Tracheoesophageal fistula: A serious complication of infectious esophagitis. Gastro~ enterology 1984;87:1174-1179

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