Esophageal candidiasis among a dyspeptic population

Ibrahim Abdulkarim Al Mofleh; Mohammad Abdullah Al Mofarreh

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Year : 1999 | Volume : 5 | Issue : 2 | Page : 61-65

Esophageal candidiasis among a dyspeptic population

Ibrahim Abdulkarim Al Mofleh¹, Mohammad Abdullah Al Mofarreh²
¹ Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia
² Dr. Al Mofarrreh's Polyclinic, Riyadh, Saudi Arabia

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Date of Submission	22-Jun-1998
Date of Acceptance	04-Jan-1999

Abstract

This is a retrospective study of 59 patients endoscoped over a period of six years at a private clinic and were found to have esophageal candidiasis. The median age was 46.38 years. Thirty (51 %) patients had no precipitating factors. Only 18 (30%) patients had typical symptoms. The distal part of the esophagus was more often involved. The thrush was scattered in 57 (97%) patients. The endoscopic finding was confirmed by cytology in all patients included. Symptoms improved on oral nystatin treatment and simultaneous treatment of associated conditions in all 46 patients followed up. In conclusion, esophageal candidiasis appear to be not uncommon among dyspeptic population. It presents more frequently with atypical symptoms and responds well to oral nystatin treatment.

How to cite this article:
Al Mofleh IA, Al Mofarreh MA. Esophageal candidiasis among a dyspeptic population. Saudi J Gastroenterol 1999;5:61-5

How to cite this URL:
Al Mofleh IA, Al Mofarreh MA. Esophageal candidiasis among a dyspeptic population. Saudi J Gastroenterol [serial online] 1999 [cited 2022 Jun 25];5:61-5. Available from: https://www.saudijgastro.com/text.asp?1999/5/2/61/33511

Candida albicans is found as a commensal in the gastrointestinal tract (GIT) in man. It has been cultured from 35-50 % of oropharyngeal washings and from 65-90 % of stool specimens obtained from healthy subjects^[1],[2],[3] . It has been found in 81 % of endoscopical samples obtained from 156 liver transplant candidates^[4] . Colonization and topical infection induce cell-mediated and antibodymediated immune responses and protect against systemic candidiasis^[5],[6],[7] . Orally immunized mice have remained chronically colonized with candida albicans without evidence of topical or systemic infection^[7]. It is unusual for candida esophagitis to develop in the absence of a predisposing factor. However, infection with candida albicans may occur in conditions associated with a congenital or acquired altered cellular immune response^[5] . In immunocompromised individuals, fungal colonization is complicated by topical infection and deeper invasion^[8] . Majority of esophageal infections are caused by candida species, predominantly candida albicans^[9] . Several factors including malignancies, especially lymphoreticular neoplasms, endocrinological disorders, malnutrition and drugs are known to enhance the susceptibility to candida infection^[10],[11] . In 963 autopsies, GIT candidiasis has been found in association with 20% of lymphosarcomas and leukemias and with 11% of Hodgkin lymphomas^[12]. Transplantation, especially of bone marrow is associated with high risk^[13] . Increased risk of candida infection has also been reported in association with systemic lupus erythematosus and chronic renal failure ^[14] . Furthermore, alcohol and advanced age have also been considered as risk factors^[15] . Opportunistic infection with candidiasis has been associated with a transient CD4 lymphocytopenia in acute and correlated with the severity of immunosuppression and persistently reduced CD4 lymphocytes count in chronic HIV infection^[16],[17] . Among various endocrinological disorders, diabetes mellitus has been associated with an impaired phagocytic and chemotactic function, and hence promoting bacterial and fungal infections^[18],[19] . Several drugs including steroids, antibiotics, cytotoxic and antisecretory agents have been implicated to predispose to esophageal candidiasis. Immunosuppressive drugs such as corticosteroids and cytotoxic agents compromise cellular immunity by lowering leucocyte count and phagocytic function^[20],[21] . While antibiotics interfere with GIT flora leading to bacterial-fungal balance alteration and fungal colonization, which may progress to infection in the presence of predisposing factors ^[21] . Hypochlorhydria, induced by H2-receptor antagonists, has been claimed earlier in the era of this medication, to enhance candida growth^[22] . This has later been confirmed by other authors^[23],[24] . It has been suggested that candida colonization complicating hypochlorhydria was responsible for a delayed healing of gastroesophageal reflux disease^[24].

Patients and methods

In this retrospective analysis of 5028 upper gastrointestinal endoscopies performed over a period of six years (1412-1418) by the same endoscopist in a gastroenterology-oriented private clinic in Riyadh, 75 patients had endoscopic diagnosis of esophageal candidiasis. This was confirmed by brush cytology in 59 patients. Patients who didn't have cytology (7) or cytology was negative (9) for candida were excluded. Endoscopy was performed after overnight fasting, utilizing 10% xylocaine spray or 2% xylocain viscous (Astra, Sweden), for local anesthesia, with an EG 2901 UGI endoscope (Pentax EPM-3000 Videoscope System). Hard point photo documentation was performed in all patients utilizing color video printer (Up-5000 P, Sony). Endoscopic fmdings were recorded considering the site and the extent of thrush as well as the presence of other endoscopic findings in the upper GIT. The presenting features, history of associated conditions and drugs were explored. All patients except one were treated with oral nystatin, 500000 units 6 hourly for 10 days. In addition concomitant endoscopic findings were treated accordingly.

Results

Over a six years period 5028 upper GIT endoscopies were performed at Dr. Al Mofarreh's polyclinic. Fifty nine patients had candidiasis proven cytotologically. Only four patients were non-Saudi nationals. The median age was 46.38 (range 18-91) years. The female to male ratio was 1:2.3. The majority of presenting features were non specific dyspeptic symptoms. Typical esophageal symptoms in form of dysphagia, retrostemal burning or pain and odynophagia were found only in 10,9 and 4 patients, respectively [Table - 1]. Twenty seven patients smoked cigarettes and three smoked shishah. Nine patients were known to have diabetes mellitus. The history of drugs is summarized in [Table - 2].

The esophageal thrush was scattered in 57 and diffuse in only two patients [Figure - 1],[Figure - 2]. Localization of thrush in esophagus is indicated in [Table - 3]. Lower esophagus, followed by lower-mid and upper-mid esophagus were more frequently involved. Concomitant endoscopic findings are shown in [Table - 4]. The distal esophagus was affected in 12/18 patients with reflux esophagitis. Helicobacter pylori

ori) was detected by Clo-test in 37 of 41 patient in whom gastric biopsy was performed. Symptomatic improvement has been recorded in all 46 patients who returned to the clinic for follow-up.

Discussion

Esophagus is the commonest site of GIT infection with candida^[25]. Candida esophagitis is the most frequent cause of infective esophagitis^[26] . It is found in about 50% of AIDS patients with esophageal symptoms^{[27],[28],[29]} . Candida esophagitis in pediatric age was found more frequently affecting the distal esophagus and presenting with hematemesis. Dysphagia and odynophagia occur in advanced stages^[30] . The adherence of candida to the esophageal mucosa has been investigated by Hoshika and Mine ^[25] . They have identified four modes of adherence in the form of mucosal attachement, subepithelial cell insertion, cavitation and invasion. Physical attachement and subepithelial invasion have been the important steps of initial adherence suggesting the importance of physical adherence prior to coloization. In a recent study on nonimmunocompromised rabitts, Hoshika et al ^[31] have found adherence by subepithelial cell insertion significantly greater than by attachment.

The prevalence of esophageal candidiasis among our upper GI endoscopy population was 1 %.Thirty patients (51%) in this series had no drugs or conditions known to precipitate candidiasis, however 19 of them were smokers. Whether nicotin alters the immune system, this question need to be answered. Among the remaining 29 (49%) patients, nine had diabetes mellitus, ten were on ranitidine, six on antibiotics, three on steroids and one patient was on cytotoxic medication. The role of antipsychiatric agents and NSAIDs lacks clarification. Although, eight patients had deranged liver function, none had clinical evidence of liver cirrhosis. The fact that most of these factors ere not inducing a severe immunosuppression was indicated by the small number of patients presenting with odynohagia and by the endoscopic appearance. Eighteen patients had 23 typical symptoms, while 41 (70%) were asymptomatic or had atypical symptoms. This is in concordance with other authors findings ^[15].

In contrast to asymptomatic esophageal colonization in immunologically intact subjects, candida esophagitis in immunocompromised patients commonly manifests with dysphagia and odynophagia^[20],[32] . Dysphagia may be preceded by retrosternal pain mimicking myocardial infarction ^[32] . The distal esophagus was more frequently involved which concord with other studies ^[30] . Although, scattered involvement of the entire esophagus was encountered in six, only two patients had a diffuse involvement. Both were heavy smokers with history of schistosomiasis in one and intake of ranitidine and antacids in the other. The presence of reflux esophagitis is expected to reduce, especially, distal esophageal infection. However two thirds of patients with reflux esophagitis had lower esophageal involvement. On the other hand, both hypochlorhydria owing to antisecretory agents and peptic esophageal strictures may promote fungal colonization and delayed healing of peptic esophagitis^[23],[33] . Although the correlation between candidiasis and H. pylori is obscure, H. pylori was found in 90% of patients, who underwent antral biopsy, which is comparable to results from dyspeptic population without candidiais^[34] . The median age of patients was 46.38 years. Advancing age is known to enhance candidiasis^[15],[35] . In our Islamic society, AIDS is very rare, therefore HIV serology was not determined in this population.

The role of radiology in diagnosis of esophageal candidiasis is limited. The sensitivity for single contrast esophagogram is 55%. However, an enhanced sensitivity (88%) may be achieved by the double contrast technique ^[36] . Endoscopy has been considered as the method of choice for diagnosis^{[11],[20],[36]} . Brush smear stained with gram stain often confirms the diagnosis^[11] . Mucosal biopsy adds further information about tissue invasion^[9],[37] . Serological detection of Mannan antigen, a candida cell wall polysaccharide confirms candida invasiveness. However due to low sensitivity and specifity its role in the diagnosis remains undetermined^[11] .

Treatment of esophageal candidiasis varies according to the severity and underlying etiology. Mild forms of esophageal candidiasis associated with antibiotics therapy may respond to cessation of antibiotics ^[38] . However, oral nystatin has been commonly used. It is effective, nonabsorbable and inexpensive^[9] . It has a fungicidal and a fungistatic activity ^[11] and does not alter the intestinal flora ^[39]. A disadvantage of oral nystatin is its unpalatable taste^[9] . All our patients except one, who didn't take the medication, were treated with oral nystatin 500,000 units 6 hourly for 10 days. All 46 patients, who came back for follow-up improved and extension of the treatment period was required in only one patient. Dyspeptic symptoms due to peptic ulcer disease and reflux esophagitis responded to treatment with antisecretory drugs with or without prokinetics.

Conclusion

Fifty one percent of patients with esophageal candidiasis in this series, had no obvious precipitating factors. The role of nicotin on the immune system require further clarification. Distal esophagus is more frequently involved. The presence of reflux esophagitis seems not to interfere with distal esophageal involvement. Although, retrosternal pain, dysphagia and odynophagia are not specific for esophageal candidiasis, however there should be a high index of suspicion particularly in association with conditions known to enhance candida growth and infection.

References

1.	Cohen R, Roth F, Delgado E, et al. Fungal flora of the normal human small and large intestine. N Engl J Med. 1969;280:638-41.
2.	Gorbach S, Nahas L, Lemer P, Weinstein L. Studies of intestinal microflora I. Gastroenterology 1967;53:845-55.
3.	Gorbach S, Plaut A, Nahas L, Weinstein L. Studies of intestinal microflora II. Gastroenterology. 1967;53:856-67.
4.	Kusne S, Tobin D, Pasculle AW, Van Thiel DH, Ho M, Starzel TE. Candida carriage in the alimentary tract of liver transplant candidates. Transplantation. 1994;57:398-402.
5.	Greenfield RA. Host defense system interactions with candida. J Med Vet Mycol. 1992;30:89-104.
6.	Fiedel PL, Sobel JD. The role of cell-mediated immunity in candidiasis. Trends Microbiol. 1994;2:202-6.
7.	Jensen J, Warner T, Johnson C, Balish E. Oral immunization of mice gainst candidiasis. J Inf Dis. 1996;174:133-40.
8.	Walsh TJ, Pizzo PA. Nosocomial fungal infections. Annue Rev Microbiol. 1988;42:517-45.
9.	Rayan KJ. Candida and other opportunistic fungi. In: Sherris JC (Ed) Medical microbiology. New York, Elsevier. 1990;47:651-60.
10.	Meunier F. Infections in patients with acute leukemia and lymphoma. In: Mandell GL, Douglas RG, Bennett JE (Eds.). Principles and practices of infectious diseases. 3rd Edn., New York, Churchill Livingstone. 1990;2265-75.
11.	Mathieson R, Dutta SK. Candida esophagitis. Dig Dis Sci. 1983;28:365-70.
12.	Eras P, Goldstein M, Sherlock P. Candida infection of the gastrointestinal tract. Medicine. 1972;51:367-79.
13.	McDonald GB, Sharma P, Hackman RC, Meyers JD, Thomas ED. Esophageal infections in immunosuppressed patients after marrow transplantation. Gastroenterology. 1985;88:1111-7.
14.	Eisenberg RL. Esophageal ulceration in gastrointestinal radiology. Philadelphia, JB Lippincott. 1990;46-69.
15.	Naito Y, Yoshikawa T, Oyamada H, et al. Esophageal candidiasis. Gastroenterol Japan. 1988;23:363-70.
16.	Decker CF, Tiernan R, Paparello SF. Esophageal candidiasis associated with acute infection due to human immunodeficiency virus. Clin Infect Dis. 1992;14:791-7.
17.	Imam N, Carpenter CCJ, Mayer KH, Fisher A, Stein M, Danforth SB. Hierarchial pattern of mucosal candida infection in HIV-seropositive women. Am J Med. 1990;89:142-6.
18.	Lehr RI. Functional aspects of a second mechanism of candidal activity by human neutrophiles. J Clin Invest. 1972;51:2566-72.
19.	Mahmoud A, Warren K, Rodman H, Mandel M. Effects of diabetes mellitus on cellular immunity. Surg Forum. 1975;26:548-50.
20.	Baehr PH, McDonald GB: Esophageal infections: risk factors, presentation, diagnosis and treatment. Gastroenterology. 1994;106:509-32.
21.	Katz P, Fauci AS. Immunosuppressives and immunoadjuvants. In: Samter M, Talmage DW, Frank MM, Austen KF, Claman HN (Eds.). Immunological diseases, 4th Ed. Boston: Little, Brown. 1988.
22.	Nicholls PE, Henry K. Gastritis and cimetidine: A possible explanation. Lancet. 1978;1:1095-6.
23.	Cipollini F, Altilia F. Candidiasis complicating cimetidine treatment. Lancet. 1981;21:1047.
24.	Vermeersch B, Rysselaere M, Dekeyser K, Rasquin K, De Vas M, Elewant A, Barbier F. Fungal colonization of the esophagus. Am J Gastroenterol.I989;84:1079-83.
25.	Hoshika K, Mine H. Significance of modes of adherence in esophageal candida albicans. J Gastroenterol. 1994;29:1-5.
26.	Yee J, Wall SD. Infections esophagitis. Radiol Clin North Am. 1994;32:1135-45.
27.	Connolly GM, Forbes A, Gazard BG. Investigation of upper gastrointestinal symptoms in patients with AIDS. AIDS. 1989;3:453-6.
28.	Porro GB, Parente F, Cemushi M. The diagnosis of esophageal candidiasis in patients with acquired immune deficiency syndrome: is endoscopy always necessary ? Am J Gastroenterol. 1989;84:143-6.
29.	Bonacini M, Laine L, Gal AA, Lee MH, Martin S, Strigle S. Prospective evaluation of blind brushings in the esophagus for candida esophagitis in patients with human immunodeficiency virus infection. Am J Gastroenterol. 1990;85:385-9.
30.	Young C, Chang MH, Chen JM. Fungal esophagitis in children. Acta Paediatr Sin. 1993;34:436-42.
31.	Hoshika K, Lida M, Mine H. Esophageal candida infection and adherence mechanisms in the noncompromised rabbit. J Gastroenterol. 1996;31:307-13.
32.	Lewicki AM, Moore FP. Esophageal moniliasis: A review of common and less frequent characteristics. AJR 1975;125:218-25.
33.	Gefter WB, Laufer I, Edell S, Gohel VK. Candidiasis in the obstructed esophagus. Radiology. 1981;138:25-8.
34.	Rashed SR, Ayoola EA, Mofleh IA, Chowdhury MN, Mahmoud K, Faleh FZ. Helicobacter pylori and dyspepsia in an Arab population. Trop Geogr Med. 1992;44:304-7.
35.	Kodsi BE, Wickremesinghe PC, Kozinn PJ, et al. Candida esophagitis. A prospective study of 27 cases. Gastroenterology. 1976;71:715-9.
36.	Levine MS, Macones AJ, Laufer I. Candida esophagitis: Accuracy of radiographic diagnosis. Radiology. 1985;154:581-7.
37.	Walsh TJ, Merz WG. Pathologic features in the human alimentary tract associated with invasiveness of Candida tropicalis. Am J Pathol. 1986;85:498-502.
38.	Woods JW, Manning IH Jr, Patterson CN. Monilial infection complicating the therapeutic use of antibiotics. JAMA.1951;145:207-11.
39.	Gilman AG, Goodman S, Gilman A. The pharmacological basis of therapeutics. 6th Edn., New York. McMillian. 1980;1232-8.