Some 50% of the normal population harbour (carry) the fungus Candida albicans as a normal oral commensal mainly on the posterior dorsum of tongue (without any disease) and are therefore termed ‘Candida carriers’. The opportunistic pathogen grows either as yeasts or hyphae (i.e. it is a dimorphic fungus). Actual infection with Candida (usually Candida albicans) is common mainly in people who are otherwise unwell; candidosis is thus called a ‘disease of the diseased’. The importance of Candida has increased greatly, particularly as the HIV pandemic extends since, when host defences are compromised, Candida typically colonizes mucocutaneous surfaces and causes only superficial infections but in immunocompromised people candidosis is commonly oro-pharyngeal and can be a portal for entry into deeper tissues and invasive candidosis (see Chs 53 and 54).
T cells and phagocytes. The full expression of phagocyte effectiveness is dependent on augmentation by cytokines synthesized or induced by T cells, such as lymphokines and IFN-γ. Polymorphonuclear leukocytes (PMNL) and macrophages phagocytose and produce cytokines, such as: myeloperoxidase, tumour necrosis factor (TNF), interferon-γ (IFN-γ), nitric oxide and granulocyte-macrophage colony stimulating factor (GM-CSF).
Hyphae invade the superficial epithelium and penetrate, via enzymes such as the phospholipases, lysophospholipases and aspartyl proteinase (secretory aspartyl proteinases; SAP) (Fig. 39.1) as far as the stratum spinosum.
C. albicans invades oral epithelial cells by inducing its own endocytosis by the adhesin and invasin Als3 and gains access to epithelial vacuolar compartments. C. albicans is internalized by oral epithelial cells through actin-dependent clathrin-mediated endocytosis and is taken into vacuolar compartments immediately following its internalization. Candida-containing endosomes transiently acquire early endosomal marker EEA1, but show marked defects in acquisition of late endosomal marker LAMP1 and lysosomal marker cathepsin D.
The innate immune system is a first-line defence and involves pattern recognition receptors such as Toll-like receptors and C-type lectin-receptors that not only induce innate immune responses but also modulate cellular and humoral adaptive immunity.
IL-12: a cytokine family which includes IL-12, IL-23, IL-27, and IL-35 – links to both innate and adaptive immunity systems. An essential component of the response that leads to the generation of Th1-type cytokine responses and protection activity against disseminated candidosis.
Th17 and release IL-17 (which recruits neutrophils), IL-21 (which stimulates CD8 or NK cells) and IL-22, the latter stimulating epithelial cells to produce proteins with antimicrobial activity against Candida.
Fungal pattern-recognition receptors such as C-type lectin receptors trigger protective Th17 responses which play the predominant role against mucosal candidiasis. IL-17A and IL-17 F are essential for mucocutaneous immunity against C. albicans
Dectin-1, a C-type lectin that recognizes 1,3-beta-glucans from fungi, including Candida, is involved in the initiation of the immune response against fungi. Patients bearing the Y238X polymorphism in the DECTIN-1 gene are more likely to be colonized with Candida species, compared with patients bearing wild-type DECTIN-1.
Activation of NF-κB and the first MAPK response, constituting c-Jun activation, is due to fungal cell wall recognition while the second MAPK phase, constituting MKP1 and c-Fos activation, depends upon hypha formation and fungal burdens – and correlates with the pro-inflammatory responses.
PMNL migrate into the epithelium in defensive mode, but candidal cell-wall mannans and glycans may impair PMNL chemotaxis, phagocytosis, respiratory burst, T lymphocyte reactivity and the macrophage secretion of tumour necrosis factor (TNF).
C. albicans is the only common cause of oral fungal or yeast infection. C. albicans can be differentiated serologically into A and B serotypes, equally distributed in healthy individuals, but there is a significant shift to type B in immunocompromised patients.
Species other than C. albicans (especially C. krusei) are increasingly seen, especially in persons with compromised immunity. In HIV disease, for example, C. dubliniensis and C. geotrichium may appear.
red lesions, in which yeast forms predominate: these include denture-related stomatitis, median rhomboid glossitis, and erythematous candidosis. These may be symptomless, although antibiotic stomatitis and angular cheilitis in particular can cause soreness.
Factors that can increase the liability to oral candidosis are shown in Box 39.1. Candidosis may also affect or spread from or to the mouth, from:
hyperplastic candidosis, which was further subdivided into four groups based on localization patterns and endocrine involvement as follows: chronic oral candidosis (Candida leukoplakia); candidosis endocrinopathy syndrome; chronic localized mucocutaneous candidosis; and chronic diffuse candidosis.
Since oral candidosis is occasionally associated with nutritional deficiencies or blood dyscrasias, estimates of haemoglobin, white blood cell counts, corrected whole blood folate, vitamin B12 and serum ferritin can be important.
|In most cases||In some cases|
|Culture and sensitivity
Full blood picture
Serum ferritin, vitamin B12 and corrected whole blood folate levels
Serology for antiacetylcholine receptor antibodies
Plasma calcium and phosphate levels
Few patients have spontaneous remission unless the condition is solely related to, for example, the use of an antimicrobial, or a topical corticosteroid, and thus, in other cases, treatment is often indicated (Table 39.2). Often, in the treatment of fungal infections, attention to the underlying cause will avoid the need for prolonged or repeated courses of treatment. Intermittent or prolonged topical antifungal treatment may be necessary where the underlying cause is unavoidable or incurable. Treatment includes the following measures:
|Regimen||Use in primary or secondary care|