Childhood oral candidiasis (oral thrush).
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Oral candidiasis is one of the more common infections encountered by man. It manifests itself in a variety of forms, and can arise in any region of the mouth. A generally innocuous and treatable disorder in healthy individuals, it can be the herald of underlying disorders that affect the endocrine or immune systems. In the debilitated or seriously ill, the capacity for seemingly benign oral candidiasis to progress into fulminating fatal infections by hematogenous dissemination must not be ignored. Oral candidiasis in the otherwise healthy patient challenges the physician's ability to identify the contributing factors and associated diseases that predispose to the infection. In the cancer and transplant patient, oral candidiasis is a harbinger of systemic infection, and has become a significant obstacle to successful management of patients with life-threatening diseases. Although several efficacious agents are available for uncomplicated candidiasis, there remains a need for better prophylactic agents to prevent dissemination and better therapeutic agents to treat established infections in immunocompromised patients.
Oral candidiasis affects both people who are immunocompromised and those who are immunocompetent and occurs in patients in hospital as well as those in the community. This article provides an overview of the pathophysiology and describes assessment and management techniques.
Oral candidiasis is a common opportunistic infection of the oral cavity caused by an overgrowth of Candida species, the commonest being Candida albicans. The incidence varies depending on age and certain predisposing factors. There are three broad groupings consisting of acute candidiasis, chronic candidiasis, and angular cheilitis. Risk factors include impaired salivary gland function, drugs, dentures, high carbohydrate diet, and extremes of life, smoking, diabetes mellitus, Cushing's syndrome, malignancies, and immunosuppressive conditions. Management involves taking a history, an examination, and appropriate antifungal treatment with a few requiring samples to be taken for laboratory analysis. In certain high risk groups antifungal prophylaxis reduces the incidence and severity of infections. The prognosis is good in the great majority of cases.
Oral candidiasis is the symptomatic development of superficial infection with many forms of clinical manifestation. The treatment of choice should include the antifungal agents which act topically in the oral cavity so that the systematic adverse effects are minimal. They should have good impregnation to the oral mucosa and prolonged effect. In patients with chronic or recurrent infection or being immunological compromised, successful treatment can be achieved by increased dosage and extended duration of antifungal therapy.
OBJECTIVES: To establish incidence rates and risk factors for HIV-associated oral candidiasis (OC), oral hairy leukoplakia (OHL), and any HIV-associated oral diseases (HIV-OD). DESIGN: This prospective, cumulative case-control study followed 283 initially oral disease-free HIV-1-infected men and women for 2 years. Incidence rate ratios (IRR) and incidence proportions for OC, OHL, and HIV-OD were estimated. Multivariable analyses using Poisson regression determined the most parsimonious best-fitting model explaining the outcomes. RESULTS: Incidence rate (per 1000 person-months) was 9.3 for OC, 6.8 for OHL, and 13.5 for HIV-OD. Incidence of OC was associated with low CD4 count (adjusted IRR = 3.0 (95% CI = 1.7, 5.1)), smoking (IRR = 1.9 (1.0, 3.8)) and combination antiretroviral therapy (IRR = 0.3 (0.1, 0.8)). Incidence of OHL was associated with low CD4 count, conditional upon smoking status. Conclusions Low CD4 count and smoking are important risk factors for HIV-associated OC and OHL. Antiretroviral medications are protective for OC but not for OHL.
OBJECTIVES: Oral candidiasis (OC) and oral hairy leukoplakia (OHL) are the most common oral mucosal diseases associated with HIV infection. Independent risk indicators associated with these sentinel opportunistic diseases have not been established in mixed race and gender adult populations in the southeast USA. The purposes of this study were 1) to estimate prevalence of OC and OHL among an HIV-1 positive adult population, and 2) to develop explanatory multivariable models for each disease outcome. METHODS: This cross-sectional study evaluated 631 adult dentate HIV-1 seropositive persons examined for HIV-associated oral mucosal diseases between 1995 and 2000 at University of North Carolina Hospitals in Chapel Hill, North Carolina using data collected from medical record review, interview questionnaire and clinical examination. We analyzed the data using t-tests, anova, and unconditional logistic regression. RESULTS: Prevalent OC was associated with low CD4+ cell count [<200 cells/microl, adj. OR = 12.7 (95%CI: 4.9-32.9)], antiretroviral combination therapy [OR = 0.6 (0.3-0.9)], and current smoking [OR = 2.5 (1.3-4.8)]. Prevalent OHL was associated with low CD4+ cell count [<200 cells/microl, OR = 7.2 (2.7-18.9)], antifungal medication use [OR = 1.8 (1.1-2.9)], current recreational drug use [OR = 2.5 (1.3-4.9)], and male gender [OR = 2.5 (1.3-4.8)]. CONCLUSIONS: While CD4+ cell count, and antiretroviral medication were important risk indicators for OC, and OHL, cigarette smoking appears to be an important risk indicator for OC in HIV-1-infected populations.
Oral epithelium reacts to microbial challenges by eliciting a defensive response that includes the production of antimicrobial peptides. This study investigated the expression of human beta-defensins-1, 2, and 3 in reconstituted human oral epithelia during experimental oral infections with six different Candida species, and a wild-type C. albicans isolate and five of its mutants. The expression of defensins was induced after 12 hours infection with the wild-type C. albicans, but this response was not seen for the noninvasive hyphal mutants nor the secreted aspartyl proteinase mutants. Furthermore, defensin expression was not detected after 48 hours in epithelia infected with either C. albicans wild-type isolate or its invasive hyphal and proteinase mutants. Most of the non-albicans Candida were capable of inducing the expression of defensins in epithelia after 24 or 48 hours of infection. These Candida-host interaction patterns suggest that the oral epithelia possess mechanisms for sensing the early invasion of C. albicans through recognition of the presence of hyphae and proteinases of Candida and respond to the insult by producing antimicrobial peptides. This hyphal-invasion-dependent inhibition of defensin expression in oral epithelium that undermines the host surveillance system represents a hitherto undescribed novel pathogenic mechanism of C. albicans.
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Oral candidiasis (OC) is a frequent side effect of inhaled corticosteroids (iCSTs). This study estimated occurrence and significance of risk factors of OC treated with antifungals in users of iCSTs under conditions of normal use. This retrospective analysis used data drawn from drug insurance plan records in Quebec, Canada. The sample contained 27,000 seniors using anti-asthma medications during 1990. Three years of data (1989-1991) were searched for use of oral antifungals concurrent with exposure to iCSTs. A case-control study examined factors leading to increased probability of first incidence of OC in new users of iCSTs. Three-year occurrence for OC was 7%. Increased risk for a first occurrence of OC was significantly associated with higher doses of iCST, increased length of iCST exposure, use of antibiotics, use of oral steroids, having three or more prescribers, a history of use of both high and low strengths of iCST, and concurrent use of oral steroids and diabetes medications. The occurrence of OC is relatively high. Knowledge of factors leading to increased risk could facilitate the targetting of patients who need timely intervention, under conditions of normal use.
In oral candidiasis, many keratinized epithelial cells and cells of Candida albicans are shed. Scales from patients with oral candidiasis were used for electron microscopic study of the epithelial-fungal relationship. Scales, scraped from the tongue and oral mucosa, were fixed for fungi. Electron microscopic observations showed cells of C. albicans outside, penetrating, or within the epithelial cells. Extracellular fungi possessed a floccular material adherent to the outer surface of the cell wall. Intracellular fungi lacked the floccular material which appeared to detach as fungi invaded the epithelial cells. Large vacuoles, which sometimes contained myelin figures, occupied the cytoplasm of fungal cells. Epithelial cells frequently contained several fungi. Discontinuous plasma membranes marked sites of fungal entry. Cytoplasmic areas devoid of fungi showed many tonofibrils, but the cytoplasm adjacent to fungi often lacked tonofibrils. Micrographs suggested that fungal cells lysed the tonofibrils. Bacteria were abundant in the scrapings, but always occupied an extracellular position.
Chronic oral candidiasis is generally not considered a premalignant condition. We report on two patients with carcinoma in situ and carcinoma in the soft palate, probably preceded by long lasting chronic Candida infection. The first patient was a 56-year-old woman who suffered from disturbances in the calcium and potassium metabolism and high blood pressure due to a previous goiter operation during which the parathyroids had been removed. She also suffered from bronchitis and had been smoking 12 cigarettes a day for many decades. For several years she had had more or less constant symptoms from airway infections. Increasing symptoms from the throat had developed 2 years before referral and, in this period, she had been in constant antifungal therapy with no effect on the symptoms. Objectively, the entire soft palate, uvula and the palatoglossal arches were fiery red with whitish plaques which were not removable (Fig. 1). A biopsy revealed severe dysplasia and focal carcinoma in situ Subsequently, the lesion in the soft palate was partly removed by laser surgery followed by radiation therapy over a period of 2 month. One year later there was no signs of recurrence (Fig. 4). The second patient, a 53-year-old healthy woman, was referred because of difficulties in eating due to pain in the throat which had existed for 2 years. Without any effect on the symptoms, she had had antifungal therapy for 4 weeks. The patient had been smoking 15 cigarettes a day for many years. Objectively, an area with whitish plaques and nodules on an erythematous background was found (Fig. 5).(ABSTRACT TRUNCATED AT 250 WORDS)
44 cases of oral candidiasis were studied histopathologically. We have found out that the microabscess in superficial epithelium is the histologic symbol of oral candidiasis. So, for those cases with microabscess, PAS stain should be done in order to make definite diagnosis. Epithelial dysplasia was observed in 8 cases (18.2%). Clinically these 8 cases were chronic hyperplastic oral candidiasis, this means that the long term follow-up study should be done for those with chronic hyperplastic oral candidiasis. Inflammatory infiltration was related to the amount of candida. The more candida get into the epithelium, the heavier inflammation is.
A conventional and easy method to establish a murine oral candidiasis model, which has not only a stable yeast population in the oral cavity but also symptoms characteristic of oral thrush, was developed by using a sedative agent. Mice were immunosuppressed with prednisolone and were given tetracycline hydrochloride. They were orally infected with 10(6) viable cells of Candida albicans by means of a cotton swab and enough chlorpromazine chloride had been injected to keep them in a sedative state about for 3 hr after inoculation. From day 3 to day 7 post inoculation, 10(5)-10(6) colony forming units of Candida were recovered from the oral cavity of each mouse and whitish, curd-like patches were observed on most parts of tongue. Microscopically, germ tubes had appeared on the tongue surface. This model would be a useful experimental oral candidiasis for investigating the pathogenesis of C. albicans oral infection and the efficacy of various antifungal agents microbiologically and symptomatically.
Many patients with oral candidiasis respond very slowly or not at all to therapy with amphotericin. Strains of Candida albicans were collected from 17 patients clinically resistant and from 15 who responded to a normal course of amphotericin treatment. Minimal inhibitory concentrations (MIC) determined on diagnostic sensitivity test agar plates gave values of: amphotericin 0-5 mg/l; nystatin 50 i.u./ml; chlorhexidine 12.5 mg/l. No clear MIC could be determined with plates containing miconazole. No difference was noted in MIC values between the 2 groups of patients. Tube-dilution tests in Sabouraud's broth gave MIC values of: amphotericin 0.25 mg/l; nystatin 12.5 i.u./ml; chlorhexidine 1.5 mg/l; miconazole 8-32 mg/l; ketonazole 64 mg/l. Persistence of oral candidiasis is not an indication of infection with resistant organisms. Despite difficulties in in vitro sensitivity testing of miconazole a clinical trial of the drug for treating oral candidiasis is indicated.
Oral candidiasis is as much the final outcome of the vulnerability of the host as of the virulence of the invading organism. We review here the extensive literature on animal experiments mainly appertaining to the host predisposing factors that initiate and perpetuate these infections. The monkey, rat, and mouse are the choice models for investigating oral candidiasis, but comparisons between the same or different models appear difficult, because of variables such as the study design, the number of animals used, their diet, the differences in Candida strains, and the duration of the studies. These variables notwithstanding, the following could be concluded. (i) The primate model is ideal for investigating Candida-associated denture stomatitis since both erythematous and pseudomembranous lesions have been produced in monkeys with prosthetic plates; they are, however, expensive and difficult to obtain and maintain. (ii) The rat model (both Sprague-Dawley and Wistar) is well proven for observing chronic oral candidal colonization and infection, due to the ease of breeding and handling and their ready availability. (iii) Mice are similar, but in addition there are well characterized variants simulating immunologic and genetic abnormalities (e.g., athymic, euthymic, murine-acquired immune deficiency syndrome, and severe combined immunodeficient models) and hence are used for short-term studies relating the host immune response and oral candidiasis. Nonetheless, an ideal, relatively inexpensive model representative of the human oral environment in ecological and microbiological terms is yet to be described. Until such a model is developed, researchers should pay attention to standardization of the experimental protocols described here to obtain broadly comparable and meaningful data.
Oral thrush is a common condition in young infants. Nystatin treatment is associated with frequent recurrences and difficulty in administration. Fluconazole was compared with nystatin for the treatment of oral candidiasis in infants. Thirty-four infants were randomized to either nystatin oral suspension four times a day for 10 days or fluconazole suspension 3 mg/kg in a single daily dose for 7 days. Clinical cures for nystatin were 6 of 19 (32%), and those for fluconazole were 15 of 15 (100%), P < 0.0001. In this small pilot study fluconazole was shown to be superior to nystatin suspension for the treatment of oral thrush in otherwise healthy infants.
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