O R A L CANDIDI ASIS

1. Introduction
⚫ Most prevalent opportunistic infection affecting oral mucosa – ‘disease of the diseased’
o Usually affects the ‘very young, very old or very weak’
1.1. Epidemiology
⚫ Prevalence of Candida species in normal oral flora is present in 35-90% people
⚫ Hospitalized patients & women have higher prevalence
1.2. Pathogenesis
⚫ C. albicans, C. tropicalis & C. glabrata comprise of over 80% of the Candida species in candidiasis
infections in humans
⚫ Other species include C. pseudotropicalis, C. krusei & C, parapsilosis
⚫ Candida species normally exists in normal flora in a vegetative state (yeast-phase cells, i.e. blastospore),
but can change to its elongated cellular form (pseudohypae) or chlamydospore form, making it
pathogenic
o Produces endotoxin (extracellular proteolytic enzyme), causing inflammation, necrosis, immune
host response, etc.
1.3. Predisposing factors
1.3.1. Local factors
⚫ Xerostomia: Due to decreased effectiveness of saliva’s antimicrobial properties
⚫ Denture wearing: Due to ill-fitting appliances, inadequate care of appliance, poor OH
⚫ Dryness
⚫ Smoking
⚫ Imbalance of oral microflora: Caused by e.g. use of mouthrinse, topical/inhalation steroids
⚫ Low pH (e.g. acidic diet, diet with high sugar level)
⚫ Radiation to head & neck: Due to xerostomia (?)
1.3.2. Systemic factors
⚫ Immunosuppressive diseases (e.g. HIV)
⚫ Impaired health status (e.g. chronic renal failure)
⚫ Immunosuppressive medication
⚫ Chemotherapy
⚫ Endocrine disorders (e.g. Diabetes mellitus, due to impaired host response)
⚫ Haematinic deficiencies (e.g. Iron, B12 & folate deficiencies)
⚫ Antibiotics therapy: Interferes with normal flora, allowing opportunistic infection by fungi
1.4. Classification
⚫ Can be classified into primary & secondary depending on the manner/extent of infection
⚫ Classic triad (either primary or secondary) of oral candidiasis are:
o Pseudomembranous
o Erythematous (atrophic)
o Hyperplastic
⚫ There’re also other Candida-associated lesions where the aetiology is multifactorial [primary oral
candidiasis]
o Antifungal therapy is not curative – the underlying aetiological co-factors that perpetuate the disease
also need to be evaluated & eradicated
❖ Candida-associated denture stomatitis
❖ Angular cheilitis/ angular stomatitis
❖ Median rhomboid glossitis
❖ Linear gingival erythema (microbiological aetiology is not conclusive)
 1.4.1. Primary oral candidiasis: Localized candida infection present only in oral & perioral tissues
⚫ Acute: Pseudomembranous, erythematous
⚫ Chronic: Pseudomembranous, erythematous, hyperplastic
⚫ Candida-associated (i.e. multi-floral): Denture stomatitis, angular cheilitis, median rhomboid
glossitis
1.4.2. Secondary oral candidiasis:
⚫ Generalized candida infections in both oral cavity & other mucocutaneous surfaces (systemic
mucocutaneous candida infections)
⚫ E.g. chronic mucocutaneous candidiasis (white lesions present on nails), DiGeorge syndrome,
candidiasis endocrinopathy syndrome
1.5. Diagnosis
⚫ Medical & general history
⚫ Clinical examination
⚫ Laboratory tests
o Smear: Pseudomembranous oral candidiasis & angular cheilitis are suspected
o Imprint culture: Adjunct in diagnostic process of erythematous candidiasis & denture stomatitis
o Salivary culture: Primarily used in parallel with other diagnostic methods for quantification of
candida
o Histopathologic examination: Identify presence of epithelial dysplasia & the invading organism in
chronic hyperplastic candidiasis
❖ Periodic acid Schiff stain is used to visualize the hyphae
o Biopsy: Reserved for hyperplastic candidiasis due to malignancy risk
⚫ Antifungal medication prescription assists in diagnosis
 1.6. Management
⚫ Identify & reduce/eradicate predisposing factors
o Leave dentures out of mouth
o Remove plaque
o Disinfect or replace dentures if necessary
o Treat underlying condition
o Smoking cessation
o Low carb diet – lower nutrients for the fungi
⚫ Antifungal medication
o Used for at least 1 week
❖ Medication is often continued for at least 1-2 weeks after symptoms subside due to high recurrent
rate
o Include
❖ Topical: Usually for localized primary infection
▪ Nystatin (oral suspension, cream,, lozenges)
 First line of treatment
 Well-tolerated
 Not associated with development of resistance
 BUT may be irritating to GI
▪ Amphotericin B (lozenges)
▪ Miconazole (2% cream)
▪ Ketoconazole (2% cream)
❖ Systemic: Usually for secondary infection e.g. immunocompromised-induced infection
▪ Fluconazole (tablets, powder)
▪ Itronazole (solution)
▪ Ketoconazole (tablets)

2. Types of oral candidiasis infection

2.1. Pseudomembranous candidiasis
⚫ Also known as ‘thrush’
⚫ Most common (35%)
⚫ Acute & chronic forms are indistinguishable
o Acute
❖ Patients taking antibiotics
❖ Patients taking immunosuppressants
❖ Patients with diseases that affect immune system
o Chronic
❖ Patients using topical/inhalation (aerosol) steroids
❖ HIV-infected individuals
❖ Immunocompromised patients
❖ Neonates, the terminally ill, esp. in association with serious underlying conditions such as leukaemia
2.1.1. Clinical features
⚫ Loosely-attached white membranes
o Usually on tongue, buccal mucosa or palate
o Can be wiped off to reveal raw, erythematous mucosa, sometimes bleeding
2.1.2. Histopathological features
⚫ White patches: Necrotic material & desquamated parakeratotic epithelium, penetrated by
yeast cells & hyphae, which invade as far as the stratum spinosum
⚫ Oropharyngeal thrush may sometimes spread into adjacent mucosa, particularly that of the upper
respiratory tract & the oesophagus
o Oral & oesophageal candidiasis is particularly prevalent in HIV disease
 2.1.3. Management
⚫ Topical antifungal preparations, mainly containing polyene drugs, e.g. nystatin & amphotericin
lozenges/pastilles

2.2. Erythematous (/atrophic) candidiasis

⚫ Associated with corticosteroids, topical/systemic broad-spectrum antibiotics, or HIV infection
⚫ May arise as
o A successor to pseudomembranous candidiasis when the pseudomembranes are shed
o Develop de novo
⚫ Often seen in palate under major maxillary connector of denture (also called denture sore mouth or
denture stomatitis)
⚫ Acute & chronic forms are also indistinguishable
2.2.1. Clinical features
⚫ Asymptomatic, erythematous areas
o Generally on dorsum of tongue, palate or buccal mucosa
o Erythematous surface may reflect atrophy as well as increased vascularization
2.2.2. Management
⚫ Topical antifungal treatment, mainly nystatin & amphotericin lozenges/pastilles
⚫ Azole group agents (e.g. oral fluconazole tablets) in case of HIV disease

2.3. Hyperplastic candidiasis

⚫ There’s correlation of hyperplastic candidiasis & malignant oral carcinogenesis
o High risk to undergo malignant transformation in long term (2-6%)
o ∴ Biopsy may be indicated
2.3.1. Clinical features
⚫ Chronic white plaque-like lesions, may be indistinguishable from oral leukoplakia
o Vary from small palpable raised areas, to large dense hard nondetachable plaque
o Often asymptomatic, occurring on the inside surface of one or both cheeks (retrocommissural
area)
⚫ Nodular lesions may also appear as speckled areas that do NOT rub off
2.3.2. Histopathological features
⚫ Parakeratosis & epithelial hyperplasia occur, with candida invasion restricted to the upper laters
of the epithelium
⚫ Associated in a minority with iron & folate deficiencies, & defective cell-mediated immunity
⚫ With varying degrees of dysplasia
2.3.3. Management
⚫ Topical antifungal treatment, mainly nystatin & amphotericin lozenges/pastilles
⚫ Azole group agents (e.g. oral fluconazole tablets): May resolve chronic infections
⚫ Follow-up for chronic areas: Due to possibility of malignant transformation

2.4. Denture stomatitis

⚫ Non-specific mucosal inflammation caused by Candida & bacterial infections
o A form of erythematous candidiasis
o Multi-floral accumulation of plaque on denture surface/underlying mucosa
⚫ Common, affects esp. otherwise healthy denture wearers
o Upper complete denture wearers (25-65%)
o Denture serves as a vehicle that protects the microbes from salivary flow & other protective
mechanism
2.4.1. Epidemiology
⚫ Common, affects esp. otherwise healthy denture wearers
o Upper complete denture wearers (25-65%)
⚫ Most frequently in maxilla (denture bearing palatal mucosa), only rarely beneath lower denture
⚫ Female > Male
2.4.2. Aetiology: Multi-factorial
2.4.2.1. Local factors
⚫ Denture wearing: Denture prevents the normal cleansing action afforded by the
movement of tongue & flow of saliva
o Denture trauma
❖ Ill-fitting dentures
❖ Incorrect jaw relationship/ occlusal errors
❖ Ecological changes brought about by 24-hour wearing of denture
o Poor denture hygiene
❖ Plaque found on the denture intaglio surface
❖ Porosity of acrylic serves as a retentive factor of plaque & pathogens
o Hypersensitivity to denture base materials
⚫ Hyposalivation & low salivary pH
2.4.2.2. Systemic factors
⚫ Nutritional status: Iron, folate, vitamin A deficiencies
⚫ Immunocompromised
o Elderly
o Diabetes mellitus
2.4.2.3. Behavioural factors
⚫ Smoking
⚫ Alcohol consumer
2.4.3. Classification
⚫ Type I: Pinpoint hyperaemia – discrete focal areas of inflammation (erythema) in palate (denture
bearing mucosa)
⚫ Type II: Generalized, diffuse & confluent erythema involving the whole (/majority) area of
mucosa covered by denture
⚫ Type III: Papillary hyperplasia & inflammation of the palate/entire denture bearing area (hard
palate & the alveolar ridge
2.4.4. Diagnosis
⚫ Clinical features: Usually asymptomatic erythematous areas on denture-bearing mucosa
⚫ Full medical history, esp. if fungal infection is suspected
o Defect in host defence mechanism
o Incorrect antibiotic therapy – use of broad-spectrum antibiotics without fungal protection
2.4.5. Complications
⚫ May progress to papillary hyperplasia & bone resorption, resulting in support deficiency
⚫ Impression on the stomatitis tissue results in unfit new denture
⚫ Angular cheilitis is disfiguring
⚫ Candida infection may become severe & widespread in medically compromised patients
2.4.6. Management
⚫ Examination of the existing dentures & correction of denture faults
o Unfit dentures
❖ Tissue conditioner (Coe-comfort)
▪ Plasticiser – may infiltrate the tissue
▪ Wears off in ~1 week; requires reapplication
❖ Chairside hard reline materials
▪ NOT soft lining materials, as they’ll act as reservoirs for microorganisms & are difficult to
disinfect
o Occlusal errors
❖ Corrected by pre-centric check-record
❖ Increase vertical dimension of denture by acrylic resin
o Ensure sufficient lip support
 ⚫ Education of patient on denture & oral hygiene
o Brush thoroughly
o Soak in disinfecting solution e.g. chlorhexidine mouthwash/ weak hypochlorite solution,
preferably overnight
o Rinse with chlorhexidine mouthwash
o Brush the affected mucosa with soft brush
o Denture should be left out at night
⚫ Antifungal treatment: If above measures fails or if fungal involvement has been confirmed (by
mycological diagnosis), usually type II & III
o Topical nystatin & amphotericin lozenges
o Miconazole: In case of angular cheilitis; antifungal & antibacterial (S. aureus)
⚫ Refer patient to specialist for suspected systemic predisposition if stomatitis still doesn’t resolve
o Iron deficiency
o High intake in carbohydrates
o Use of antibiotics, corticosteroids & immunosuppressive drugs
⚫ Fabricate new dentures only after the denture stomatitis has resolved

2.5. Angular cheilitis (/stomatitis)

⚫ Infected commissures at on or both angle of the mouth, often with erythema
⚫ Associated with both Candida & Staph. aureus
⚫ Often occurs as a complication of Candida-associated denture stomatitis
⚫ May be associated with dry skin, vitamin B12 & iron deficiencies, HIV
o The disease resolves when the underlying condition is treated
⚫ May also be associated with loss of vertical dimension, esp. in elderly whose found with overclosure of
lips, leading to accentuation of skin folds at the corner of mouth
o Saliva leaks into these folds, resulting in maceration of the skin, breakdown of the epithelium &
infection with Candida from the intra-oral reservoir
2.5.1. Clinical features
⚫ Soreness, erythema, fissuring
2.5.2. Histopathological features
⚫ Candida spp. are present with or without co-infection with Staph. aureus
⚫ The presence of yellow crusting may indicate staphylococcal infection
2.5.3. Management
⚫ Elimination of the intraoral reservoir of infection in concurrent denture stomatitis
⚫ Adjustment of vertical dimension of dentures
o To prevent salivary retention & moisture at the angles of mouth (as moist body surfaces
encourage the growth of Candida)
⚫ Medication
o Topical antifungal therapy
❖ Nystatin
❖ Amphotericin B
❖ Miconazole: With both antifungal & anti-staphylococcal activity; useful for mixed infections
o Anti-staphylococcal preparations (dictated by microbiological investigation)
❖ Fusidic acid
❖ Neomycin/chlorhexidine
o Investigate for possible underlying disease: Iron/vitamin B12 deficiencies, HIV infection, etc.
2.6. Median rhomboid glossitis
⚫ Predisposing co-factors: Smoking, steroid inhalation, remnants of the tuberculum impar
⚫ The lesion may spontaneous remit
2.6.1. Clinical features
⚫ Oval/rhomboid erythematous lesion
o At the midline in the centre or posterior dorsum of tongue
o Atrophy of filiform papillae resulting in smooth shiny surface
o Asymptomatic
⚫ Concurrent erythematous lesions may be observed in palatal mucosa as well
2.6.2. Histopathological features
⚫ Frequently shows a mixed bacterial-fungal microflora
2.6.3. Management
⚫ Oral hygiene instruction
⚫ Antifungal therapy

2.7. Linear gingival erythema

⚫ A localized or generalized erythematous band extending along the gingival margin (between adjacent
gingival papilla
⚫ Seen in, but not confined to, HIV-infected individuals
⚫ Lesions resolve after antifungal therapy, but other co-factors, e.g. oral hygiene also play an important role