REVIEWCytotoxic drugs, radiotherapy and oral candidiasis
Introduction
Candidiasis is the most common oral fungal infection in man and manifests in a variety of clinical guises ranging from pseudomembraneous (thrush), erythematous, and hyperplastic variants to more recently described linear gingival erythema associated with HIV infection.[1], [2] All forms of oral candidiasis are considered opportunistic as a multiplicity of predisposing factors facilitate conversion of commensal Candida into a parasitic existence. HIV-infected individuals develop oral candidiasis, as one of the commonest and earliest manifestations.[2], [3] The increasing prevalence of other compromised patient groups in the community, common endocrine disorders such as diabetes mellitus, and nutritional deficiencies have also contributed to the resurgence of oral candidiasis as a relatively common affliction.1 Further, candidiasis can manifest as an oral adverse effect of drug therapy following usage of broad-spectrum antibiotics, corticosteroides and cytotoxics.4
Cytotoxic drugs have a major dampening effect on the cell-mediated arm of the immune component5 and patients receiving such therapy are particularly vulnerable to fungal and viral infections.6 For instance, in one prospective cohort study on orofacial complications of combination chemotherapy (cyclophosphamide, methotrexate, flurouracil, vincristine and prednisone) in women with breast cancer McCarthy et al.7 found intra-oral candidiasis in 12% of their cohort. The increased incidence of oral candidiasis seen in patients with malignancies stems partly from such therapeutic measures and partly form radiotherapy, which are either used singly or in combination depending on factors such as the type, stage, and severity of malignancy. In addition the concurrent administration of broad-spectrum antibiotics may further predispose the patient to oral candidiasis.8 As noted below the incidence of oral candidiasis vary widely in individuals with malignancies and this is likely to be due to the wide disparities in the clinical regimens used in different parts of the world[9], [10], [11], [12] as well as the varying laboratory techniques used in yeast isolation.
In this brief review we discuss the clinical and mycological findings on the relationship between cytotoxics, radiotherapy and oral candidiasis and outline the possible aetiopathogenic mechanisms. The management of oral candidiasis following these therapeutic measures is also addressed with a concluding section on future research directions in this arena.
Section snippets
Clinical aspects
Early studies have shown that Candida species are responsible for approximately one half of oral infections that arise during antileukaemic chemotherapy, and for almost two thirds in patients on antineoplastic drugs for solid tumours.13 For instance, in a study of 1000 hospitalized adult patients with acute and chronic leukaemia, 33% developed oral infections in which 50% of the infecting organisms were fungi, mainly Candida species.14 In another study of 906 adult in-patients receiving
Animal studies
The relationship between cytotoxics, immunosuppressants and oral candidiasis in animal models has been studied by a few workers (for a recent review see Samaranayake and Samaranayake29). Various animals such as Sprague–Dawley rats, mice and guinea pigs have been used for these experiments, some examples of which follows.
Samaranayake et al.,30 used two groups of Sprague–Dawley rats to investigate mucosal candidiasis consequential to intermittent oral inoculation of either C. albicans or Candida
Mechanisms of pathogenicity
The mechanisms by which therapeutic procedures for oral and other forms of cancer favour the oral yeast carriage or infection are likely to be complex (Fig. 1). It is highly likely that the yeast proliferation (infestation) as well as the subsequent infection is related to both the host factors related to the cancer itself and, the side-effects of antineoplastic therapy.4
Host defenses that are critical to shield against the development of candidiasis, are an adequate number of circulating
Preventive measures
Autopsy data have shown that 5%, 12% and 25% of patients with solid tumours, lymphomas, and leukaemias, respectively had histological evidence of invasive fungal infections and, 58% of such infections were caused by Candida species.40 Another survey of autopsy examination results indicates that the minimal risk of a fatal systemic candidal infection in leukaemic patients is 27%.41 It is also known that Candida could persorb through intact gastrointestinal mucosa and cause transient candidaemias.
Conclusions
The current data provide us but a glimpse of the relationship between cytotoxics, radiotherapy and oral candidiasis in malignancy. Further studies are direly needed to fully illustrate the reasons for the candidal proliferation under these circumstances as large numbers of these patients are likely to be seen in future due to technological and life-saving advances of modern medicine. The advent of new molecular tools and deciphering the candidal genome should help in this direction not only to
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