Oral Candidiasis (Adult)

Overview

Oral candidiasis, commonly known as oral thrush, is a fungal infection of the oral mucosa caused predominantly by Candida albicans (80-90% of cases), with non-albicans species including C. glabrata, C. tropicalis, and *C. krusei accounting for the remainder. [1,2] This opportunistic infection represents one of the most common oral mucosal diseases and serves as an important clinical marker of immunosuppression, particularly in HIV/AIDS, where it occurs in 75-90% of patients during the course of their disease. [3,4]

The condition presents with a spectrum of clinical manifestations ranging from asymptomatic white patches to painful erythematous lesions that significantly impact quality of life, nutrition, and speech. [5] While often regarded as a minor infection in immunocompetent individuals, oral candidiasis can herald serious underlying systemic disease, progress to invasive oesophageal or systemic candidiasis in the immunocompromised, and contribute to treatment-resistant biofilm formation on dental prostheses and oral appliances. [6,7]

Recognition of clinical subtypes, understanding of host risk factors, and knowledge of emerging antifungal resistance patterns are essential for effective diagnosis and management. The increasing prevalence of fluconazole-resistant Candida species, particularly in patients with recurrent or chronic disease, poses significant therapeutic challenges and necessitates familiarity with alternative treatment strategies. [8,9]

---

Epidemiology

Oral candidiasis affects diverse patient populations with variable incidence based on immune status and local risk factors.

Key Epidemiological Features

Age Distribution: Bimodal distribution affecting neonates/infants and elderly populations, with a significant peak in immunocompromised adults aged 20-50 (HIV/AIDS) and over 65 (multimorbidity). [1,10]

Gender: No significant gender predilection in immunocompetent hosts, though denture-related candidiasis shows slight female predominance (2:1) due to higher denture usage rates. [12]

Geographic Variation: Universal distribution with higher reported prevalence in resource-limited settings due to HIV burden and reduced access to antiretroviral therapy and antifungal medications. [19]

Temporal Trends: Declining incidence in HIV-positive populations in developed countries following widespread antiretroviral therapy (ART) implementation (50-70% reduction since mid-1990s), but persistent high rates in sub-Saharan Africa and Southeast Asia. [11,20]

---

Aetiology & Pathophysiology

Causative Organisms

Primary pathogen: Candida albicans (80-90% of cases) - most virulent species with superior adhesion, hyphal formation, and biofilm production capabilities. [1,2]

Non-albicans species (increasing prevalence, particularly in fluconazole-exposed patients): [8,9]

• C. glabrata (5-10%): intrinsically reduced azole susceptibility
• C. tropicalis (2-5%): associated with severe immunosuppression
• C. krusei (1-3%): intrinsically fluconazole-resistant
• C. dubliniensis (\u003c5%): phenotypically similar to C. albicans, HIV-associated

Pathophysiological Mechanisms

Colonisation to infection transition: Candida species exist as oral commensals in 30-60% of healthy adults. [10] Disease occurs when host defences are compromised, allowing fungal overgrowth and tissue invasion.

Host defence mechanisms (when intact, prevent disease):

• Intact epithelial barrier with antimicrobial peptides (β-defensins, histatins)
• Salivary flow and IgA antibodies providing mechanical clearance and immune surveillance
• Resident oral microbiota competitive inhibition
• Cell-mediated immunity (Th1 and Th17 responses) controlling fungal burden [21]

Virulence factors enabling invasion:

• Adhesins (Als proteins, Hwp1): mediate attachment to oral epithelial cells and denture surfaces
• Morphological switching: yeast-to-hyphal transition enables tissue penetration [2,22]
• Biofilm formation: creates drug-resistant communities on mucosal surfaces and prostheses [6,7]
• Secreted proteinases and phospholipases: degrade epithelial barriers and immune proteins

Exam Detail: Molecular mechanisms of host-pathogen interaction:

Epithelial invasion pathway: Following adhesion via Als3 and Hwp1 adhesins, C. albicans undergoes morphogenesis from yeast to hyphal forms in response to environmental cues (37°C, pH 7, serum). [22] Hyphae penetrate between epithelial cells via active penetration (thigmotropism) and induced endocytosis, triggering NLRP3 inflammasome activation and IL-1β/IL-17 release.

Immune evasion strategies:

• Surface masking of β-glucan (PAMPs) by mannan layer, evading dectin-1 recognition
• Secretion of proteinases degrading complement proteins and antimicrobial peptides
• Phenotypic switching (white-opaque switching) modulating immunogenicity [2]

Biofilm architecture: Mature Candida biofilms consist of basal yeast cells, intermediate hyphal layers, and superficial extracellular matrix rich in β-1,3-glucans and extracellular DNA. [6,7] This structure limits drug penetration (fluconazole MIC increases 1000-fold in biofilms) and protects against host phagocytes.

HIV-associated immunopathology: Progressive CD4+ T-cell depletion impairs Th1 and Th17 responses critical for antifungal defence. [3,4] Oral candidiasis typically emerges when CD4 counts fall below 200 cells/μL and becomes increasingly severe and treatment-refractory below 50 cells/μL, correlating with loss of Candida-specific T-cell responses.

Risk Factors

Systemic immunosuppression:

• HIV/AIDS (CD4 \u003c200 cells/μL) [3,4]
• Haematological malignancy and chemotherapy-induced neutropenia [17]
• Solid organ and haematopoietic stem cell transplantation
• Systemic corticosteroid therapy (\u003e20 mg prednisolone equivalent daily)
• Immunosuppressive medications (methotrexate, biologics, JAK inhibitors)
• Primary immunodeficiencies (chronic mucocutaneous candidiasis, APECED syndrome)

Local factors:

• Inhaled corticosteroids without spacer device or mouth rinsing [14,15]
• Xerostomia (Sjögren's syndrome, medications, radiotherapy, age-related)
• Removable dental prostheses, especially with continuous 24-hour wear [12,13]
• Poor oral hygiene and untreated dental caries
• Smoking (alters oral microbiome and impairs local immunity)

Metabolic factors:

• Diabetes mellitus (particularly HbA1c \u003e8%) [16]
• Nutritional deficiencies (iron, folate, vitamin B12)
• Extremes of age (infants, elderly)

Antimicrobial use:

• Broad-spectrum antibiotics disrupting oral microbiota
• Previous/chronic antifungal exposure selecting resistant strains [8,9]

---

Clinical Presentation

Clinical Classification

Oral candidiasis manifests in several distinct clinical forms, each with characteristic appearances and associations.

1. Pseudomembranous Candidiasis (Thrush)

Classic presentation: Creamy-white, curd-like plaques on any oral mucosal surface (buccal mucosa, tongue, palate, oropharynx). [1,5]

Key features:

• Plaques easily scraped off, revealing erythematous or bleeding base
• May be asymptomatic or associated with burning sensation, altered taste
• Most common form in acute immunosuppression (HIV, chemotherapy, corticosteroids)
• Can extend to oropharynx and oesophagus in severe cases

Clinical significance: Indicates active fungal proliferation with substantial organism burden; presence suggests significant immunocompromise if no other risk factors present.

2. Erythematous (Atrophic) Candidiasis

Acute form: Smooth, red, atrophic patches on tongue (median rhomboid glossitis pattern) or palate. [1,5]

Key features:

• No white plaques; flat, red, sensitive areas
• Common after antibiotic therapy or with inhaled corticosteroid use
• Painful, burning sensation, dysgeusia
• Dorsum of tongue appears smooth due to depapillation

Chronic form:

• Denture stomatitis (see below)
• Angular cheilitis-associated palatal erythema

Clinical significance: Often underdiagnosed due to absence of white plaques; requires high clinical suspicion in at-risk patients presenting with oral discomfort.

3. Chronic Hyperplastic Candidiasis (Candidal Leukoplakia)

Presentation: Firm, white, adherent plaques that cannot be scraped off, typically on buccal mucosa or lateral tongue. [1,5]

Key features:

• Chronic lesion persisting for months to years
• Strong association with smoking
• Requires biopsy to exclude dysplasia or malignancy
• Premalignant potential: 5-15% risk of malignant transformation [23]

Clinical significance: The only form of oral candidiasis with malignant potential; mandates biopsy and long-term surveillance.

4. Angular Cheilitis (Perleche)

Presentation: Erythema, fissuring, and crusting at the oral commissures, often bilateral. [1,5]

Key features:

• May be candidal alone or mixed Candida/Staphylococcus aureus infection
• Associated with overclosure (denture wearers, edentulous patients), drooling, nutritional deficiency
• Painful, interferes with mouth opening and eating
• Chronic cases develop radiating fissures and scarring

Predisposing factors: Denture wear, vitamin B12/iron deficiency, reduced vertical dimension of occlusion.

5. Denture Stomatitis (Chronic Atrophic Candidiasis)

Presentation: Erythema and oedema of palatal mucosa in precise contact area with denture (typically maxillary). [12,13]

Classification (Newton's):

• Type I: Localised pinpoint hyperaemia
• Type II: Diffuse erythema under denture-bearing area
• Type III: Granular/papillary hyperplasia (inflammatory papillary hyperplasia)

Key features:

• Often asymptomatic; discovered on examination
• Strong association with continuous (24-hour) denture wear and poor denture hygiene
• Candida biofilm formation on denture fitting surface [6,7]

Clinical significance: Primarily a denture hygiene issue requiring both antifungal therapy and prosthesis management.

Symptom Profile

Physical Examination Findings

General inspection:

• Assess hydration status and salivary flow (xerostomia predisposes)
• Look for cachexia or signs of systemic illness (HIV, malignancy)
• Examine lips for angular cheilitis

Oral cavity examination:

• Tongue: White plaques (pseudomembranous), red depapillated areas (erythematous), median rhomboid glossitis
• Buccal mucosa: Plaques, erythema, white lines (exclude lichen planus)
• Palate: Erythema (especially under denture), plaques
• Oropharynx: Extension of plaques (suggests oesophageal involvement risk)

Denture assessment (if applicable):

• Remove dentures and examine fitting surface for debris and biofilm
• Assess palatal mucosa for type of denture stomatitis
• Evaluate denture fit and hygiene practices

Red flag signs requiring urgent investigation:

• ⚠️ Dysphagia: Suggests oesophageal candidiasis [24]
• ⚠️ Fevers, weight loss: Consider invasive disease or underlying malignancy
• ⚠️ Non-healing ulcers: Exclude malignancy, especially in chronic hyperplastic form [23]
• ⚠️ First presentation in previously healthy adult: Investigate for HIV, diabetes, malignancy

---

Differential Diagnosis

Key Differentials by Presentation

For White Lesions (Pseudomembranous Candidiasis)

For Red Lesions (Erythematous Candidiasis)

For Angular Lesions (Angular Cheilitis)

Must-Not-Miss Diagnoses

1. Oral squamous cell carcinoma: Especially in chronic hyperplastic candidiasis or non-healing ulcers in high-risk patients (smoking, alcohol, HPV). [23]
2. HIV/AIDS: New-onset oral candidiasis in young adult with no other risk factors mandates HIV testing. [3,4]
3. Poorly controlled diabetes: May be first presentation of undiagnosed diabetes mellitus. [16]
4. Underlying haematological malignancy: Acute leukaemia presenting with oral candidiasis and neutropenia. [17]

---

Investigations

Clinical Diagnosis

In most cases, oral candidiasis is a clinical diagnosis based on:

• Characteristic appearance (scrapable white plaques or erythematous patches)
• Presence of risk factors (immunosuppression, dentures, inhaled steroids)
• Response to empirical antifungal therapy [1,5]

Microbiological Confirmation

Indications for laboratory investigation:

• Atypical appearance or diagnostic uncertainty
• Failure of first-line empirical therapy
• Recurrent or chronic infection (exclude fluconazole resistance) [8,9]
• Immunocompromised hosts (guide species-specific therapy)
• Chronic hyperplastic candidiasis (exclude malignancy)

Smear and Microscopy

Technique: Scrape lesion with tongue depressor or swab; prepare smear for KOH 10% mount or Gram stain.

Findings:

• Budding yeast cells and pseudohyphae confirm Candida presence
• Sensitivity: 70-85% [1]
• Advantages: Rapid (minutes), inexpensive, point-of-care
• Limitations: Cannot speciate or determine susceptibility

Oral Swab Culture

Technique: Firmly swab affected area; send for fungal culture on Sabouraud dextrose agar.

Results:

• Species identification (C. albicans vs non-albicans)
• Quantification (light/moderate/heavy growth)
• Sensitivity: 85-95% [1]
• Turnaround: 48-72 hours

Interpretation:

• Heavy growth supports diagnosis (distinguishes from commensal carriage)
• Species identification guides therapy (e.g., C. krusei is intrinsically fluconazole-resistant)

Antifungal Susceptibility Testing

Indications: [8,9]

• Treatment failure with first-line azole therapy
• Recurrent infection in HIV/AIDS or other immunocompromised
• Non-albicans species isolated
• Chronic suppressive therapy requirement

Methods: Broth microdilution, E-test, automated systems (VITEK)

Interpretation:

• Reports minimum inhibitory concentration (MIC) for fluconazole, itraconazole, voriconazole, echinocandins
• C. glabrata: often dose-dependent susceptibility or resistance to fluconazole
• C. krusei: intrinsically fluconazole-resistant

Biopsy

Indications:

• Chronic hyperplastic candidiasis: Mandatory to exclude dysplasia or malignancy [23]
• White plaques that do NOT scrape off
• Non-healing ulcers or atypical lesions
• Suspected dual pathology (e.g., candidiasis complicating lichen planus)

Histopathology findings:

• PAS or GMS staining demonstrates fungal hyphae invading epithelium
• Assess for epithelial dysplasia or malignancy
• Evaluate underlying mucosal pathology

Investigation for Underlying Cause

First presentation or recurrent disease: [3,4,16]

---

Management

Management requires addressing both the Candida infection and underlying predisposing factors.

General Principles

1. Identify and modify risk factors: Optimise glycaemic control, review medications, improve oral hygiene
2. Choose appropriate antifungal: Based on clinical form, severity, immune status, and resistance patterns
3. Duration: Adequate treatment course (typically 7-14 days) to prevent relapse
4. Denture management: Essential in denture-related disease
5. Consider prophylaxis: In select high-risk populations

Topical Antifungal Therapy

First-line for mild-moderate disease in immunocompetent patients. [1,5]

Nystatin Suspension

• Dose: 100,000 units/mL; use 4-6 mL QDS; swish and swallow (or spit if denture stomatitis only)
• Duration: 7-14 days, continue 48 hours after resolution
• Mechanism: Polyene binds ergosterol in fungal cell membrane
• Advantages: Minimal systemic absorption, safe in pregnancy, broad Candida coverage
• Limitations:
  • Poor palatability (sucrose-based; avoid in diabetes or use sugar-free formulation)
  • Requires QDS dosing and good compliance
  • Less effective than azoles in severe or oropharyngeal disease

Miconazole Oromucosal Gel

• Dose: 2.5 mL (125 mg) QDS applied to affected areas; retain in mouth before swallowing
• Duration: 7 days, continue 7 days after resolution
• Advantages: Well tolerated, QDS dosing, some systemic absorption (reaches oropharynx)
• Limitations:
  • "Drug interactions: Potent CYP3A4 inhibitor; avoid with warfarin (INR increase), statins, certain antiretrovirals [25]"
  • Contraindicated in porphyria
  • Less effective in severe immunosuppression

Amphotericin Lozenges

• Dose: 10 mg QDS; dissolve slowly in mouth
• Duration: 10-14 days
• Advantages: Broad-spectrum polyene, effective for azole-resistant species
• Limitations: Availability limited in some countries; poor palatability

Topical therapy considerations:

• ✅ Suitable for mild-moderate pseudomembranous or erythematous candidiasis
• ✅ Preferred in pregnancy and breastfeeding
• ❌ Inadequate for oesophageal extension or severe immunosuppression
• ❌ Poor efficacy in chronic hyperplastic candidiasis

Systemic Antifungal Therapy

Indications: [1,5,8]

• Moderate-severe disease
• Immunocompromised hosts (HIV, neutropenia, transplant)
• Oropharyngeal or oesophageal involvement
• Failure of topical therapy
• Angular cheilitis (requires systemic levels)
• Chronic hyperplastic candidiasis

Fluconazole (First-line systemic agent)

• Dose:
  • "Mild-moderate: 50-100 mg PO once daily for 7-14 days"
  • "Severe or HIV-associated: 100-200 mg PO once daily for 7-14 days [3,4]"
  • "Oesophageal candidiasis: 200-400 mg PO once daily for 14-21 days [24]"
• Advantages:
  • Excellent oral bioavailability (\u003e90%)
  • Good tissue penetration
  • Once-daily dosing
  • Generally well tolerated
• Limitations:
  • Resistance in C. glabrata, intrinsic resistance in C. krusei [8,9]
  • Drug interactions (CYP3A4 and CYP2C9 substrate; QT prolongation)
  • Hepatotoxicity (monitor LFTs in prolonged therapy)
  • "Pregnancy: Avoid (especially first trimester); associated with cardiac/skeletal abnormalities at high doses"

Alternative Systemic Azoles

Itraconazole solution:

• Dose: 200 mg PO once daily (or 100 mg BD) for 14 days
• Indications: Fluconazole-resistant cases, C. glabrata
• Considerations: Better absorption with acidic environment (take with food or acidic drink); avoid PPI/H2RA; monitor LFTs

Posaconazole suspension:

• Dose: 400 mg PO BD for 1 day, then 400 mg once daily; take with food
• Indications: Refractory disease, fluconazole-resistant isolates
• Considerations: Broad-spectrum triazole; expensive; reserve for refractory cases

Voriconazole:

• Dose: 200 mg PO BD
• Indications: Invasive or refractory candidiasis
• Considerations: Potent CYP interactions; visual disturbances; photosensitivity; hepatotoxicity

Echinocandins (Rarely Required for Oral Disease)

• Agents: Caspofungin, micafungin, anidulafungin
• Indications: Severely immunocompromised with azole-resistant isolates or invasive disease
• Limitations: IV administration only; expensive; reserve for refractory/systemic cases

Exam Detail: Fluconazole Resistance Mechanisms: [8,9]

Resistance to fluconazole has emerged as a significant problem, particularly in HIV/AIDS patients with recurrent disease receiving repeated or prolonged courses.

Mechanisms:

1. Efflux pump upregulation: CDR1, CDR2 (ABC transporters) and MDR1 (MFS transporter) overexpression actively pumps fluconazole out of cell
2. Target enzyme alteration: ERG11 (lanosterol 14α-demethylase) mutations reduce azole binding
3. Bypass mechanisms: ERG3 mutations alter ergosterol biosynthesis pathway
4. Biofilm formation: Extracellular matrix limits drug penetration [6,7]

Species-specific resistance patterns:

• C. albicans: Acquired resistance following azole exposure (5-10% of HIV isolates in heavily exposed populations)
• C. glabrata: Intrinsically reduced susceptibility; dose-dependent or resistant (MIC \u003e32 μg/mL)
• C. krusei: Intrinsically fluconazole-resistant (MIC \u003e64 μg/mL)
• C. auris: Emerging multidrug-resistant species (rare in oral disease but increasing global concern)

Clinical approach to suspected resistance:

• Send cultures for species identification and susceptibility testing
• Switch to itraconazole solution, posaconazole, or amphotericin if azole-resistant
• Consider echinocandin in severe immunosuppression with proven resistance
• Address biofilm sources (dentures, dental appliances)

Denture Hygiene and Management

Essential for denture stomatitis treatment and prevention. [12,13]

Denture hygiene protocol:

1. Remove dentures at night: Allow mucosal recovery; soak overnight in disinfectant
2. Daily mechanical cleaning: Brush with soft brush and non-abrasive denture cleaner (NOT regular toothpaste)
3. Disinfection: Soak in chlorhexidine 0.2% or sodium hypochlorite 0.02% (dilute Milton 1:80) for ≥8 hours overnight [12]
   • Chlorhexidine: Effective against Candida biofilms, well tolerated, does not damage acrylic
   • Sodium hypochlorite: Highly effective but may corrode metal clasps in partial dentures
4. Microwave disinfection (if facilities available): 650W for 3 minutes in water bath (kills Candida in biofilm)

Combined antifungal therapy:

• Topical to mucosa: Miconazole gel or nystatin to palate QDS
• Topical to denture: Apply thin layer of antifungal to fitting surface before insertion
• Systemic: Fluconazole 50-100 mg daily if topical fails or extensive disease

Denture replacement: Consider if dentures are old, ill-fitting, porous, or heavily colonised with biofilm resistant to cleaning.

Management by Clinical Form

Special Populations

HIV/AIDS Patients [3,4,11]

• First episode: Fluconazole 100-200 mg daily for 7-14 days
• Recurrent disease (≥2 episodes/year):
  • Treat acute episode as above
  • "Consider secondary prophylaxis: Fluconazole 100-200 mg 3x/week OR daily if CD4 \u003c50"
  • "Prophylaxis discontinuation: Can stop when CD4 \u003e200 for ≥3 months on ART [11]"
• Azole-refractory disease: Culture/susceptibility; consider itraconazole solution, posaconazole, or amphotericin
• Immune reconstitution: ART optimisation reduces recurrence by 70-90%

Pregnancy and Breastfeeding

• Preferred: Topical therapy (nystatin, miconazole gel)
• Avoid: Fluconazole (teratogenic risk, especially high doses/first trimester) [25]
• If systemic required: Consider risk-benefit; miconazole gel has some oral absorption (alternative to fluconazole)

Elderly and Care Home Residents [18]

• High prevalence due to multimorbidity, polypharmacy, xerostomia
• Topical therapy first-line if compliant
• Fluconazole easier for compliance (once daily)
• Address xerostomia (saliva substitutes, medication review), nutritional status

Diabetes Mellitus [16]

• HbA1c optimisation is crucial (target \u003c58 mmol/mol, 7.5%)
• Standard antifungal therapy as per clinical form
• Educate on association between hyperglycaemia and infection risk

Prophylaxis

Indications for antifungal prophylaxis:

• HIV/AIDS: CD4 \u003c50-100 with recurrent episodes (fluconazole 100-200 mg 3x/week or daily) [3,4,11]
• Chemotherapy/HSCT: Fluconazole or posaconazole during high-risk neutropenic period [17]
• Inhaled corticosteroids: Spacer device use and mouth rinsing (non-pharmacological prophylaxis) [14,15]

Concerns with prophylaxis:

• Risk of selecting fluconazole-resistant Candida species [8,9]
• Use lowest effective dose for shortest necessary duration
• Reassess need regularly (e.g., discontinue when HIV CD4 \u003e200 for 3 months on ART)

---

Complications

---

Prognosis

Natural History

Untreated: Symptoms may wax and wane but typically persist or worsen in presence of ongoing risk factors. Spontaneous resolution is uncommon unless predisposing factor removed.

With Treatment:

• Immunocompetent: Excellent prognosis; \u003e90% clinical cure with appropriate therapy [1,5]
• HIV/AIDS: Depends on immune reconstitution; ART reduces recurrence by 70-90% [11]
• Denture stomatitis: Recurrence common (50-70%) without ongoing denture hygiene [12,13]

Prognostic Factors

Favourable:

• Immunocompetent host
• Removable predisposing factor (e.g., antibiotic course completed)
• C. albicans infection (fluconazole-sensitive)
• Good treatment adherence

Poor/Recurrent Disease:

• Severe immunosuppression (HIV CD4 \u003c50, neutropenia \u003c0.5) [3,4]
• Non-albicans species, especially fluconazole-resistant strains [8,9]
• Inability to address underlying risk factors (continued inhaled steroids, denture wear, xerostomia)
• Biofilm-associated disease (dentures, oral appliances)

Long-term Follow-up

• Chronic hyperplastic candidiasis: Long-term surveillance for malignant transformation; annual review with biopsy of suspicious areas [23]
• HIV/AIDS: Monitor CD4 count; adjust prophylaxis as per immune status [11]
• Denture wearers: Regular dental review; reinforce hygiene practices
• Recurrent disease: Investigate for undiagnosed immunosuppression, diabetes, or emerging resistance

---

Prevention & Screening

Primary Prevention

General measures:

• Maintain good oral hygiene: regular brushing, flossing, dental check-ups
• Avoid unnecessary antibiotic use
• Control diabetes: aim HbA1c \u003c58 mmol/mol (7.5%) [16]

Inhaled corticosteroid users: [14,15]

• Use spacer device (reduces oropharyngeal deposition by 70-80%)
• Rinse mouth thoroughly with water after each use and spit out
• Brush teeth after use if possible
• Use lowest effective dose of inhaled steroid

Denture wearers: [12,13]

• Remove dentures at night (minimum 6-8 hours denture-free period)
• Daily cleaning with denture brush and cleaner
• Overnight soaking in chlorhexidine 0.2% or dilute hypochlorite
• Regular dental review for denture fit and oral health

Xerostomia management:

• Saliva substitutes and stimulants (sugar-free gum, pilocarpine)
• Medication review to minimise anticholinergic burden
• Frequent sips of water

Secondary Prevention (Prophylaxis)

See Management section above for specific indications.

Non-pharmacological:

• Probiotics containing Lactobacillus species: Some evidence for reducing Candida colonisation in denture wearers (quality of evidence modest) [26]

Screening

• No routine screening in asymptomatic populations
• High-risk groups: Regular oral examination in HIV/AIDS, chemotherapy, transplant patients as part of standard care [3,4,17]

---

Key Guidelines

International Guidelines

1. British Society for Medical Mycology (2012): Management of oral and oesophageal candidiasis

   • Fluconazole first-line for systemic therapy
   • Topical therapy adequate for mild disease in immunocompetent
   • Emphasises denture hygiene

2. Infectious Diseases Society of America (IDSA, 2016): Clinical Practice Guideline for Candidiasis [27]

   • Fluconazole 100-200 mg daily for 7-14 days for oropharyngeal candidiasis
   • Clotrimazole troches or nystatin suspension for topical therapy
   • Itraconazole or posaconazole for fluconazole-refractory disease
   • Amphotericin B oral suspension or echinocandin for azole-resistant cases

3. European Federation of Periodontology/European Association of Oral Medicine (2019): Management of oral candidiasis in denture wearers

   • Combined approach: antifungal + denture hygiene
   • Chlorhexidine denture soaking effective
   • Overnight denture removal essential [12]

4. WHO (2018): Guidelines on HIV-related oral disease

   • Screen all HIV patients for oral candidiasis at each visit
   • Fluconazole 100-200 mg daily for 7-14 days
   • Secondary prophylaxis for recurrent disease; stop when CD4 \u003e200 × 3 months [11]

---

Clinical Examination Technique

Systematic Oral Cavity Examination

A thorough oral examination is essential for accurate diagnosis and classification of oral candidiasis.

Preparation:

• Good lighting (headlight or examination light)
• Tongue depressor
• Gloves
• Gauze (for tongue examination)
• Consider taking photographs (with consent) for documentation

Systematic approach:

Step 1: External Examination

• Lips: Inspect for angular cheilitis (erythema, fissuring, crusting at commissures)
• Perioral skin: Assess for angular lesions extending beyond oral commissures
• Lymph nodes: Palpate submandibular, submental, and cervical lymph nodes (usually not enlarged in uncomplicated oral candidiasis; enlargement suggests secondary bacterial infection or underlying malignancy)

Step 2: Anterior Oral Cavity

• Labial mucosa: Retract lips; inspect upper and lower labial mucosa for plaques or erythema
• Buccal mucosa: Ask patient to open mouth; retract cheeks bilaterally; examine entire buccal surface
  • Note distribution of lesions (unilateral vs bilateral, localized vs diffuse)
  • "Scraping test: Gently scrape white lesions with tongue depressor"
    • ✓ Candidiasis: Lesions scrape off, revealing erythematous or bleeding base
    • ✗ Leukoplakia/lichen planus: Lesions do NOT scrape off
• Gingivae: Examine marginal and attached gingiva for erythema, swelling

Step 3: Tongue Examination

• Dorsum:
  • Inspect for white plaques (pseudomembranous)
  • Look for depapillated red areas (erythematous/atrophic)
  • Assess for median rhomboid glossitis (diamond-shaped depapillated area in midline posterior dorsum)
• Lateral borders: Important site for chronic hyperplastic candidiasis; requires biopsy if white adherent plaques present
• Ventral surface: Ask patient to lift tongue to roof of mouth; inspect ventral surface and floor of mouth
• Tongue mobility: Gently grasp tongue with gauze; extend to visualize posterior tongue and oropharynx

Step 4: Palate Examination

• Hard palate: Inspect for erythema, plaques
• Soft palate: Assess for erythema, oedema, plaques
• If denture wearer: ALWAYS remove dentures to examine underlying mucosa
  • Assess pattern of erythema (confined to denture-bearing area = denture stomatitis)
  • "Classify denture stomatitis (Newton):"
    • Type I: Localized pinpoint hyperaemia
    • Type II: Diffuse erythema covering denture area
    • Type III: Granular, cobblestone appearance (inflammatory papillary hyperplasia)
  • "Examine denture: Inspect fitting surface for debris, biofilm, rough areas"

Step 5: Oropharyngeal Examination

• Tonsillar pillars and tonsils: Depress tongue with tongue depressor; ask patient to say "Ahhh"
• Posterior pharyngeal wall: Look for extension of plaques (suggests risk of oesophageal involvement)
• Note: Presence of oropharyngeal candidiasis increases risk of oesophageal candidiasis, especially in HIV/AIDS

Step 6: Saliva Assessment

• Salivary flow: Observe pooling of saliva; ask patient about dry mouth symptoms
• Xerostomia testing:
  • Palpate major salivary glands (parotid, submandibular) for enlargement
  • Milk submandibular duct (Wharton's duct) to assess secretions
• Clinical signs of xerostomia: Dry, sticky mucosa; lack of saliva pooling in floor of mouth; tongue adheres to buccal mucosa

Documentation

Record findings systematically:

"Oral examination: Bilateral creamy-white plaques on buccal mucosa and dorsum of tongue, easily scraped off with tongue depressor revealing erythematous base. Bilateral angular cheilitis present with erythema and fissuring at oral commissures. Oropharyngeal examination shows extension of plaques to tonsillar pillars. Salivary flow appears adequate. Cervical lymph nodes not palpable. Impression: Pseudomembranous oral candidiasis with angular cheilitis, consistent with immunosuppression. Query HIV status."

---

Patient Education and Counseling

For All Patients with Oral Candidiasis

Explanation of condition: "You have a fungal infection called oral thrush caused by a yeast called Candida. This yeast normally lives in your mouth without causing problems, but it has overgrown due to [identify specific risk factor: your weakened immune system/recent antibiotics/inhaled steroid use/denture wear]. The infection causes the white patches and sore areas in your mouth."

Treatment expectations:

• "The antifungal medication will clear the infection, usually within 7-14 days"
• "It's important to complete the full course even if symptoms improve earlier, to prevent the infection coming back"
• "You should notice improvement in symptoms (reduced soreness, better taste) within 2-3 days"
• "If no improvement after 3-4 days, or symptoms worsen, contact us for review"

Prevention:

• Maintain good oral hygiene: brush teeth twice daily, floss daily
• Attend regular dental check-ups
• Avoid smoking (damages oral tissues and immune defenses)
• Stay well hydrated
• [Address specific risk factors as below]

For Inhaled Corticosteroid Users

Counseling on inhaler technique and mouth care: [14,15]

"Your inhaled steroid for asthma/COPD can increase risk of oral thrush because it deposits in your mouth and reduces local immune defenses. To prevent this:

1. Use a spacer device: This reduces the amount of steroid deposited in your mouth by 70-80%. [Demonstrate spacer use if available]

2. Rinse your mouth thoroughly after EVERY use:

   • Swish water vigorously around your mouth for 10-15 seconds
   • Spit out the water (do not swallow)
   • Repeat rinse 2-3 times
   • If possible, brush your teeth after using your inhaler

3. Timing: Use your inhaler before meals when possible, so you can rinse and brush afterwards

4. Continue your inhaler: Do NOT stop your asthma/COPD medication. With proper technique and mouth care, you can prevent thrush while keeping your breathing condition controlled

5. Report symptoms early: If you notice mouth soreness, white patches, or altered taste, see your doctor promptly for treatment"

For Denture Wearers

Comprehensive denture hygiene counseling: [12,13]

"Your denture is contributing to the oral infection because Candida forms a biofilm (sticky layer) on the denture surface that is hard to remove. To treat the infection AND prevent it coming back, you need to follow this denture care routine:

1. Remove dentures at night (ESSENTIAL):

• Take out your dentures for at least 6-8 hours overnight
• This allows your mouth tissues to recover and reduces Candida growth
• Sleep without dentures; it will not affect your jaw or facial appearance

2. Clean dentures daily:

• Remove and rinse dentures after meals
• Brush ALL surfaces with a denture brush and denture cleaner (NOT regular toothpaste, which can scratch the denture)
• Pay special attention to the fitting surface that touches your palate

3. Soak dentures overnight in disinfectant:

• Use chlorhexidine 0.2% mouthwash OR diluted Milton (1 capful in 80ml water)
• Place dentures in solution for at least 8 hours (overnight)
• Rinse thoroughly before reinserting in the morning
• Change solution daily

4. Clean your mouth:

• Brush your gums, tongue, and palate with a soft toothbrush morning and night (even without teeth)
• Rinse mouth before reinserting dentures

5. Store dentures properly:

• When not wearing, store in water or disinfectant solution (never let them dry out)
• Keep denture container clean

6. See your dentist:

• Have your dentures checked annually for proper fit
• Ill-fitting dentures cause trauma and increase infection risk
• Dentures typically need replacing every 5-7 years

What happens if I don't follow this routine? The antifungal medication will temporarily clear the infection, but it WILL come back (50-70% recurrence rate) if denture hygiene is not maintained. The biofilm on your denture acts as a reservoir for the fungus."

For HIV-Positive Patients

Counseling on oral candidiasis and immune health: [3,4,11]

"Oral thrush is common in people with HIV when the CD4 count (immune cells) is low, usually below 200. The good news is:

1. Treatment works well: The antifungal medication [fluconazole] will clear this infection within 1-2 weeks

2. Antiretroviral therapy (ART) is the most important prevention:

• ART raises your CD4 count and restores your immune system
• Once your CD4 count rises above 200 for at least 3 months, your risk of thrush drops by 70-90%
• Taking ART consistently is the best way to prevent oral thrush from coming back

3. When do you need preventive medication?:

• If you have thrush episodes frequently (≥2 times per year), we may recommend taking fluconazole 2-3 times per week to prevent recurrence
• Once your CD4 count is consistently above 200 on ART, we can usually stop the preventive medication

4. Watch for warning signs:

• If you develop difficulty or pain swallowing, this suggests the thrush may have spread to your oesophagus (food pipe)
• Contact us immediately if this occurs, as it requires higher doses of medication

5. Oral hygiene:

• Brush teeth twice daily
• See a dentist regularly (every 6 months)
• Report any new mouth sores, lumps, or persistent white patches

6. Your CD4 count today is [X]:

• [If \u003c200]: "This is why you developed thrush. Starting/optimizing ART will help prevent future episodes"
• [If \u003e200]: "Your CD4 count is good, so this episode is less likely to recur once treated. Make sure you continue taking ART consistently"

Questions to ask:

• "Are you currently taking ART? What is your regimen?"
• "How is your adherence? Are you able to take all doses?"
• "When was your last CD4 count and viral load check?"
• "Have you had thrush before? How many episodes in the past year?"

For Diabetic Patients

Link between diabetes control and infection risk: [16]

"Your diabetes increases your risk of oral thrush because high blood sugar levels:

• Impair your immune system's ability to fight infections
• Increase glucose in saliva, which Candida yeast uses as food to multiply

To prevent oral thrush from recurring:

1. Optimize your diabetes control:

   • Aim for HbA1c below 58 mmol/mol (7.5%)
   • Monitor your blood sugars regularly
   • Take your diabetes medications consistently
   • Follow dietary advice

2. Oral hygiene is extra important for diabetics:

   • Brush teeth twice daily with fluoride toothpaste
   • Floss daily
   • See your dentist every 6 months (diabetics have higher risk of gum disease too)

3. Stay alert for infections:

   • Check your mouth regularly for white patches, sore areas, or bleeding gums
   • Report any new mouth symptoms to your doctor
   • If thrush keeps coming back, this may be a sign your diabetes needs better control

We will:

• Check your HbA1c today to see how well your diabetes has been controlled over the past 3 months
• Review your diabetes medications
• Refer you to the diabetes team if needed for better glucose control"

---

Management Algorithms

Algorithm 1: Initial Assessment and Treatment Selection

ORAL CANDIDIASIS SUSPECTED
        ↓
Clinical Diagnosis
  • Characteristic appearance (white plaques OR erythema)
  • Risk factors present
  • ± Scraping test (plaques remove?)
        ↓
Classify Clinical Form
  • Pseudomembranous
  • Erythematous  
  • Chronic hyperplastic → BIOPSY REQUIRED
  • Angular cheilitis
  • Denture stomatitis
        ↓
Assess Severity & Immune Status
        ↓
┌───────────────┴───────────────┐
│                               │
MILD + IMMUNOCOMPETENT    MODERATE-SEVERE OR IMMUNOCOMPROMISED
│                               │
Topical Therapy               Systemic Therapy
• Nystatin suspension OR      • Fluconazole 50-200 mg daily
• Miconazole gel              • Duration: 7-14 days
• Duration: 7-14 days         • Higher doses (200 mg) for HIV/severe
│                               │
└───────────────┬───────────────┘
                ↓
        Address Risk Factors
          • Denture hygiene
          • Inhaler technique  
          • Diabetes control
          • HIV: ART optimization
                ↓
        Review at 1-2 weeks
                ↓
        ┌───────┴───────┐
        │               │
    RESOLVED      NOT RESOLVED
        │               │
  Reinforce         Send culture
  prevention      Assess adherence
                  Consider:
                  • Species ID
                  • Susceptibility
                  • Alternative agent
                  • Biopsy if atypical

Algorithm 2: Management of Treatment-Refractory Oral Candidiasis

ORAL CANDIDIASIS NOT RESPONDING TO FIRST-LINE THERAPY
        ↓
Review Diagnosis
  • Is this definitely candidiasis? (consider lichen planus, leukoplakia)
  • Biopsy if uncertain or chronic hyperplastic form
        ↓
Assess Treatment Adherence
  • Did patient complete full course?
  • Correct dosing and duration?
  • Drug interactions (e.g., PPI reducing azole absorption)?
        ↓
Send Microbiological Samples
  • Oral swab for culture
  • Species identification
  • Antifungal susceptibility testing
        ↓
Identify Persisting Risk Factors
  • Denture biofilm not addressed?
  • Poor denture hygiene ongoing?
  • Severe immunosuppression (HIV CD4 \u003c50, neutropenia)?
  • Uncontrolled diabetes (HbA1c \u003e8%)?
  • Continued xerostomia?
        ↓
Culture Results Available
        ↓
┌───────────────┴───────────────────┬─────────────────────┐
│                                   │                     │
C. ALBICANS (Fluconazole-resistant) NON-ALBICANS SPECIES  NO GROWTH
│                                   │                     │
Options:                          Options:              Reconsider diagnosis
• Itraconazole solution 200 mg PO • C. glabrata:        • Viral (HSV, CMV)
  daily × 14 days                   - Itraconazole OR   • Bacterial
• Posaconazole 400 mg PO daily      - High-dose         • Lichen planus
• Amphotericin B suspension         fluconazole         • Leukoplakia
• Echinocandin (if severe)          (\u003e400mg) OR       • Malignancy
                                    - Echinocandin      → Biopsy
                                  • C. krusei:
                                    - Itraconazole OR
                                    - Voriconazole OR
                                    - Echinocandin
                                    (NO fluconazole)
                                  • C. auris:
                                    - Echinocandin
                                    (often MDR)
        │                             │
        └─────────────┬───────────────┘
                      ↓
            Address Biofilm Sources
              • Replace/disinfect dentures
              • Remove/replace oral appliances
              • Microwave denture disinfection
                      ↓
            Consider Specialist Referral
              • Infectious diseases (HIV, complex resistance)
              • Oral medicine (chronic/recurrent disease)
              • Immunology (if recurrent + no obvious cause)

Algorithm 3: HIV/AIDS Oral Candidiasis Management Pathway

HIV-POSITIVE PATIENT WITH ORAL CANDIDIASIS
        ↓
Check CD4 Count & Viral Load
        ↓
┌───────┴─────────┬──────────────┐
│                 │              │
CD4 \u003e200       CD4 100-200    CD4 \u003c100
│                 │              │
First episode?  First episode? Likely recurrent
Low recurrence   Moderate risk  High risk
risk                           Oesophageal?
        ↓               ↓              ↓
    TREATMENT       TREATMENT      TREATMENT
    Fluconazole     Fluconazole    Fluconazole
    100 mg daily    100-200 mg     200 mg daily
    × 7-14 days     × 7-14 days    × 14 days
        │               │              │
        └───────────────┴──────────────┘
                        ↓
            Is patient on ART?
                        ↓
        ┌───────────────┴───────────────┐
        │                               │
    YES - On ART                    NO - Not on ART
    Check adherence & VL           START ART urgently
        │                           (CD4 \u003c200)
        ↓                               ↓
  VL suppressed?                  Counsel on ART
        ↓                         Refer to HIV clinic
    ┌───┴────┐                        │
    │        │                        │
   YES      NO                        │
    │        │                        │
Excellent  Poor adherence             │
Continue   Adherence                  │
ART       support                     │
    │        │                        │
    └────┬───┘                        │
         └────────────────────────────┘
                    ↓
        Monitor for Recurrence
                    ↓
        ┌───────────┴──────────┐
        │                      │
    NO RECURRENCE      RECURRENT (≥2/year)
        │                      │
    Continue ART         Start Prophylaxis
    Regular f/u          Fluconazole 100-200 mg
    CD4 monitoring       • 3×/week if CD4 50-200
                         • Daily if CD4 \u003c50
                                │
                                ↓
                        Re-assess every 3-6 months
                                ↓
                        CD4 \u003e200 × 3 months on ART?
                                ↓
                            ┌───┴───┐
                            │       │
                           YES     NO
                            │       │
                    STOP prophylaxis Continue
                    Continue ART     prophylaxis
                    Monitor          Monitor CD4

---

Case-Based Scenarios

Case 1: Inhaled Corticosteroid User

Clinical Scenario: A 62-year-old woman with COPD presents with a 5-day history of sore mouth and altered taste. She uses beclometasone 200 μg BD via metered-dose inhaler without a spacer. She does not rinse her mouth after use. She is otherwise well, non-diabetic, and denies recent antibiotics.

On examination: Smooth, red, atrophic patches on dorsum of tongue and hard palate. No white plaques visible. Buccal mucosa appears normal.

Questions:

1. What is the most likely diagnosis?
2. What clinical form of oral candidiasis is this?
3. What is the underlying mechanism?
4. What is your management plan?

Model Answers:

1. Diagnosis: Erythematous (atrophic) oral candidiasis secondary to inhaled corticosteroid use

2. Clinical form: Erythematous candidiasis—characterized by red, atrophic areas WITHOUT white plaques. This form is associated with antibiotic use and inhaled steroids, and is often underdiagnosed due to absence of classic white patches.

3. Mechanism: Inhaled corticosteroids deposit on oral mucosa, causing local immunosuppression. This impairs cell-mediated immunity and reduces antimicrobial peptide production, allowing Candida overgrowth. Without spacer use or mouth rinsing, the oropharyngeal deposition rate is high (60-80%), significantly increasing risk. [14,15]

4. Management:

   • Antifungal therapy:

     • First-line: Miconazole oromucosal gel 2.5 mL QDS × 7-14 days OR
     • Fluconazole 50 mg once daily × 7 days (preferred for compliance)
     • Check for drug interactions (miconazole with warfarin, statins)

   • Inhaler technique optimization (ESSENTIAL to prevent recurrence):

     • Prescribe spacer device: Reduces oropharyngeal deposition by 70-80%
     • Demonstrate spacer technique: Shake inhaler → attach to spacer → actuate once → inhale slowly → hold breath 10 seconds
     • Mouth rinsing protocol: Rinse vigorously with water immediately after each use, spit out, repeat 2-3 times
     • Timing: Use inhaler before meals when possible, allowing tooth brushing after

   • Patient education: Explain the link between inhaler and oral thrush; emphasize that proper technique allows safe continuation of essential respiratory medication

   • Follow-up: Review at 1-2 weeks to confirm resolution and check inhaler technique. If recurrent despite optimal technique, consider switching to alternative inhaler formulation or lower dose if asthma/COPD control permits.

Key learning points:

• Erythematous candidiasis presents WITHOUT white plaques (often missed)
• Inhaled steroids are common cause; spacer device reduces risk by 70-80%
• Patient education on inhaler technique is as important as antifungal therapy

---

Case 2: HIV/AIDS with Low CD4 Count

Clinical Scenario: A 34-year-old man with known HIV presents with painful mouth and difficulty swallowing for 2 weeks. He was diagnosed with HIV 6 months ago but has not started antiretroviral therapy due to poor engagement with clinic. His most recent CD4 count was 85 cells/μL.

On examination: Extensive creamy-white plaques on buccal mucosa, tongue, and palate, easily scraped off. Bilateral angular cheilitis present. Oropharyngeal examination shows plaques extending to tonsillar pillars and posterior pharynx. He has odynophagia on swallowing water.

Questions:

1. What is the diagnosis and significance?
2. How do you classify severity?
3. What is your management plan?
4. What are the long-term strategies to prevent recurrence?

Model Answers:

1. Diagnosis: Severe pseudomembranous oral candidiasis with probable oesophageal extension in advanced HIV/AIDS (CD4 85)

   Significance:

   • Oral candidiasis at CD4 \u003c200 indicates significant immunosuppression [3,4]
   • Odynophagia suggests oesophageal candidiasis (occurs in 15-30% of HIV patients with oropharyngeal disease, especially CD4 \u003c100) [24]
   • Marker of poor HIV control and need for urgent ART initiation
   • Risk of further opportunistic infections

2. Severity classification:

   • Severe oropharyngeal candidiasis (extensive mucosal involvement, angular cheilitis, symptomatic)
   • Probable oesophageal candidiasis (odynophagia in setting of oropharyngeal disease + CD4 \u003c100)
   • CD4 \u003c100: High-risk category for complications and recurrence

3. Immediate management:

   Antifungal therapy:

   • Fluconazole 200-400 mg PO once daily (higher dose for presumed oesophageal involvement)
   • Duration: 14-21 days (longer course for oesophageal disease)
   • Response assessment: Should improve within 3-4 days
   • If no improvement: Consider endoscopy to confirm oesophageal candidiasis vs alternative diagnosis (CMV oesophagitis, HSV oesophagitis, aphthous ulcers)

   Symptomatic relief:

   • Analgesia: Paracetamol ± codeine for odynophagia
   • Dietary modification: Soft, cool foods; avoid spicy/acidic foods
   • Maintain hydration and nutrition

   Urgent HIV management:

   • Start ART immediately: WHO/BHIVA guidelines recommend ART initiation regardless of CD4 count, especially with opportunistic infection
   • Counsel on importance of adherence
   • Screen for other opportunistic infections (TB, PCP, toxoplasmosis)
   • Initiate Pneumocystis prophylaxis (co-trimoxazole 960 mg daily) if not already on it (indicated for CD4 \u003c200)

   Baseline investigations:

   • Repeat CD4 count and HIV viral load
   • Check for other OIs: CXR (PCP, TB), serum cryptococcal antigen if symptomatic
   • Liver function tests (baseline before ART and azole therapy)

4. Long-term prevention strategies:

   Primary strategy—ART optimization: [11]

   • Ensure ART started and adherence supported (pill boxes, reminders, directly observed therapy if needed)
   • Target viral suppression (\u003c50 copies/mL)
   • Monitor CD4 recovery (expect rise of 50-100 cells/μL/year)
   • ART reduces oral candidiasis recurrence by 70-90%

   Secondary antifungal prophylaxis (for recurrent disease): [3,4,11]

   • Indication: ≥2 episodes per year
   • Regimen: Fluconazole 100-200 mg three times weekly OR daily if CD4 \u003c50
   • Discontinuation criteria: CD4 \u003e200 cells/μL for ≥3 months on ART with viral suppression

   Patient education:

   • Explain link between low CD4 and infections
   • Emphasize ART as definitive solution
   • Oral hygiene: brush BD, dental review every 6 months
   • Report new symptoms early (dysphagia, weight loss, fevers)

   Multidisciplinary care:

   • Link with HIV specialist clinic
   • Adherence support worker
   • Peer support groups

Key learning points:

• Oropharyngeal candidiasis + odynophagia at CD4 \u003c100 = presumed oesophageal candidiasis
• Treat with high-dose fluconazole (200-400 mg) for 14-21 days
• ART is the MOST important long-term intervention
• Prophylaxis indicated for recurrent disease; discontinue once immune reconstitution achieved

---

Case 3: Denture Stomatitis

Clinical Scenario: An 81-year-old woman presents for routine dental check. She is asymptomatic. She wears a full upper denture continuously (24 hours/day) and removes it briefly for cleaning by rinsing under tap water. On examination, there is diffuse erythema and mild oedema of the entire palatal mucosa in precise distribution matching denture-bearing area (Newton Type II denture stomatitis). The denture fitting surface shows white debris and biofilm.

Questions:

1. What is the diagnosis and classification?
2. Why is denture hygiene important in this condition?
3. What is your comprehensive management plan?
4. What advice do you give to prevent recurrence?

Model Answers:

1. Diagnosis: Denture stomatitis (chronic atrophic candidiasis), Newton Type II

   Classification (Newton):

   • Type I: Localized pinpoint areas of hyperaemia
   • Type II: Diffuse erythema covering entire denture-bearing area ← This case
   • Type III: Granular, cobblestone appearance (inflammatory papillary hyperplasia); may require surgical intervention

2. Importance of denture hygiene:

   Candida biofilm on dentures is central to pathogenesis and recurrence: [6,7,12,13]

   • Biofilm formation: Candida adheres to acrylic denture surface, forming complex biofilm with bacterial species. Biofilm protects organisms from antifungal agents and immune defenses.

   • Reservoir for reinfection: Denture biofilm acts as continuous source of Candida reinfecting palatal mucosa. Antifungal therapy treats mucosal infection but does NOT eradicate denture biofilm.

   • Drug resistance: Biofilm-associated Candida exhibits 1000-fold increased resistance to fluconazole compared to planktonic cells

   • Recurrence without denture management: Studies show 50-70% recurrence if dentures not properly managed, even with appropriate antifungal therapy

   • Mechanical trauma: Continuous denture wear (24 hrs) causes chronic trauma, mucosal hypoxia, and reduced salivary clearance, creating environment conducive to Candida proliferation

3. Comprehensive management:

   A. Antifungal therapy:

   • Topical (first-line for asymptomatic/mild):

     • Miconazole gel 2.5 mL QDS: Apply to palate AND thinly to denture fitting surface before insertion
     • Duration: 14-28 days (longer than oral forms due to biofilm)

   • Systemic (if extensive or topical fails):

     • Fluconazole 50-100 mg once daily × 14 days

   B. Denture hygiene protocol (ESSENTIAL):

   1. Overnight denture removal:

      • Remove for minimum 6-8 hours (ideally overnight)
      • Allows mucosal recovery and oxygenation
      • Reduces Candida proliferation

   2. Daily mechanical cleaning:

      • Brush ALL denture surfaces (especially fitting surface) with soft denture brush
      • Use denture cleaner or liquid soap (NOT abrasive toothpaste which scratches acrylic, creating niches for biofilm)
      • Rinse thoroughly

   3. Chemical disinfection (critical for biofilm eradication):

      • Chlorhexidine 0.2% solution: Soak denture for ≥8 hours overnight
        • Effective against Candida biofilms
        • Does not damage acrylic or corrode metal clasps (safe for partial dentures)
      • OR Sodium hypochlorite (dilute Milton 1:80 or bleach 1:10): Soak ≥8 hours
        • Highly effective but may corrode metal clasps (avoid for partial dentures with metal framework)
      • Change solution daily
      • Rinse denture before reinserting

   4. Microwave disinfection (if available):

      • Submerge denture in water in microwave-safe container
      • Microwave at 650W for 3 minutes
      • Kills Candida in biofilm
      • Do NOT microwave dentures with metal components

   C. Oral mucosal care:

   • Brush palate, gums, tongue with soft toothbrush after denture removal (removes Candida, stimulates circulation)
   • Rinse mouth before reinserting dentures

   D. Denture assessment and replacement:

   • Refer to dentist for assessment of denture fit, retention, occlusion
   • Check for sharp areas, overextension causing trauma
   • Replace denture if:
     • Old (\u003e5-7 years; acrylic becomes porous with age, harboring biofilm)
     • Ill-fitting (causing chronic trauma)
     • Heavily colonized biofilm resistant to cleaning
     • Cracked or damaged

   E. Systemic factors:

   • Check for xerostomia (common in elderly; saliva substitutes/stimulants)
   • Review medications (anticholinergics, diuretics causing dry mouth)
   • Screen for diabetes if recurrent (fasting glucose or HbA1c)

4. Prevention advice:

   "Mrs [Name], your palate infection is caused by a yeast that grows on your denture. To prevent it coming back:

   • MOST IMPORTANT: Remove your denture every night for at least 6-8 hours. This allows your palate to recover. Sleeping with dentures actually increases infection risk 5-6 fold.

   • Soak your denture overnight in chlorhexidine mouthwash (I'll prescribe this). This kills the yeast biofilm. Just rinsing under water is NOT enough.

   • Brush your denture daily with a denture brush. Clean all surfaces, especially the part that touches your palate.

   • Clean your mouth too: Brush your gums and palate with a soft toothbrush after removing dentures.

   • See your dentist annually to check denture fit. We may need to replace your dentures every 5-7 years.

   If you follow this routine, the infection will clear and stay away. But if you continue wearing your dentures 24 hours and just rinsing them, the infection will keep coming back."

Key learning points:

• Denture stomatitis requires BOTH antifungal therapy AND denture hygiene modification
• Continuous denture wear and inadequate cleaning are primary risk factors
• Denture biofilm must be addressed; antifungals alone have 50-70% recurrence rate
• Patient education on overnight removal and chemical disinfection is critical

---

Common Exam Questions

Written Exam Questions (SBAs/MCQs)

1. What is the most common causative organism of oral candidiasis in adults?

   • Answer: Candida albicans (80-90% of cases) [1,2]

2. At what CD4 count does oral candidiasis typically occur in HIV-positive patients?

   • Answer: \u003c200 cells/μL (occurs in 75-90% during disease course) [3,4]

3. Which Candida species is intrinsically resistant to fluconazole?

   • Answer: Candida krusei (also C. auris; C. glabrata has reduced susceptibility) [8,9]

4. What is the first-line systemic treatment for oral candidiasis in an immunocompetent adult?

   • Answer: Fluconazole 50-100 mg once daily for 7-14 days [1,5]

5. Which form of oral candidiasis has premalignant potential?

   • Answer: Chronic hyperplastic candidiasis (5-15% malignant transformation risk) [23]

6. What is the recommended disinfectant for denture soaking to prevent candidiasis?

   • Answer: Chlorhexidine 0.2% or sodium hypochlorite (dilute) for ≥8 hours overnight [12,13]

7. A patient on inhaled beclometasone develops oral candidiasis. What is the best preventive measure?

   • Answer: Use spacer device and rinse mouth after each use (reduces deposition 70-80%) [14,15]

8. When can antifungal prophylaxis be discontinued in an HIV patient on ART?

   • Answer: When CD4 count \u003e200 cells/μL for ≥3 months [11]

9. What percentage of HIV/AIDS patients develop oral candidiasis during disease course?

   • Answer: 75-90% [3,4]

10. Angular cheilitis is best treated with:

    • Answer: Systemic fluconazole (topical does not reach adequate levels at commissures)

Clinical Exam/OSCE Stations

1. Examine this patient with a sore mouth and describe your findings.

   • Systematic approach: lips → buccal → tongue (dorsum, lateral, ventral) → palate → oropharynx
   • Remove dentures if present
   • Perform scraping test
   • Document findings accurately

2. This patient with HIV (CD4 50) has recurrent oral thrush. How would you manage?

   • Assess current episode: extent, oesophageal symptoms
   • Antifungal: Fluconazole 200 mg daily × 14 days
   • ART: Review regimen and adherence
   • Prophylaxis: Fluconazole 100-200 mg daily (CD4 \u003c50)
   • Screen for other OIs
   • Long-term: ART optimization to raise CD4 \u003e200

3. Counsel this patient on proper inhaler technique and mouth care to prevent oral candidiasis.

   • Demonstrate spacer use
   • Explain mouth rinsing protocol (after EVERY use)
   • Timing (before meals, brush teeth after)
   • Reassure: can continue inhaler safely with proper technique
   • Provide written instructions

4. Demonstrate how to advise a denture wearer on cleaning and caring for dentures.

   • Remove overnight (6-8 hours minimum)
   • Daily brush with denture brush
   • Overnight soak in chlorhexidine or dilute hypochlorite
   • Clean mouth (brush gums, palate)
   • Store in water/solution
   • Annual dental check

Viva Voce Questions

1. Describe the clinical forms of oral candidiasis.

   • Pseudomembranous (white plaques, scrapable)
   • Erythematous/atrophic (red patches, no plaques)
   • Chronic hyperplastic (adherent white, premalignant)
   • Angular cheilitis (commissures)
   • Denture stomatitis (palatal erythema under denture)

2. What are the risk factors for developing oral candidiasis?

   • Systemic: HIV (\u003cCD4 200), diabetes, immunosuppression, antibiotics
   • Local: Dentures, inhaled steroids, xerostomia, poor hygiene
   • Host: Extremes of age, nutritional deficiencies

3. Explain the mechanisms of fluconazole resistance in Candida species.

   • Efflux pumps (CDR1/2, MDR1) upregulation
   • Target site alteration (ERG11 mutations)
   • Bypass pathways (ERG3 mutations)
   • Biofilm formation [8,9]

4. When would you use topical versus systemic antifungal therapy?

   • Topical: Mild-moderate, immunocompetent, localized disease, pregnancy
   • Systemic: Moderate-severe, immunocompromised, oesophageal extension, angular cheilitis, treatment failure

5. What is your approach to a patient with chronic hyperplastic candidiasis?

   • Biopsy mandatory (exclude dysplasia/malignancy) [23]
   • Antifungal: Fluconazole 100-200 mg × 14-28 days
   • Risk factors: Smoking cessation critical
   • Long-term surveillance (annual review, biopsy suspicious areas)
   • If persistent after antifungal: Surgical excision

---

---

Viva Points

Viva Point: Opening statement: "Oral candidiasis is an opportunistic fungal infection of the oral mucosa caused predominantly by Candida albicans, occurring in approximately 75-90% of patients with advanced HIV/AIDS and presenting with diverse clinical forms ranging from pseudomembranous thrush to denture-related stomatitis."

Key facts to mention:

• C. albicans accounts for 80-90% of cases; non-albicans species (glabrata, tropicalis, krusei) are increasing [1,2]
• CD4 count \u003c200 cells/μL is the typical threshold for oral candidiasis in HIV [3,4]
• Five main clinical forms: pseudomembranous, erythematous, chronic hyperplastic, angular cheilitis, denture stomatitis [1,5]
• Chronic hyperplastic form has 5-15% malignant transformation risk and requires biopsy [23]
• Topical therapy (nystatin, miconazole) first-line for mild disease; systemic fluconazole for moderate-severe or immunocompromised [1,5]
• Denture hygiene is essential: remove overnight, clean daily, soak in chlorhexidine 0.2% [12,13]
• Fluconazole resistance emerging in C. glabrata (dose-dependent/resistant) and intrinsic in C. krusei [8,9]
• Inhaled steroid users should use spacers and rinse mouth after use [14,15]

Structured management approach:

1. Diagnosis: Clinical (characteristic appearance + risk factors); consider swab/culture if atypical or treatment failure
2. Severity assessment: Extent, symptoms (dysphagia suggests oesophageal involvement), immune status
3. Treatment selection:
   • Mild + immunocompetent: Topical (nystatin, miconazole)
   • Moderate-severe OR immunocompromised: Fluconazole 100-200 mg daily × 7-14 days
4. Address predisposing factors: Denture hygiene, inhaler technique, diabetes control, medication review
5. Follow-up: Ensure resolution; biopsy if chronic hyperplastic form; investigate underlying immunosuppression if recurrent

Red flags:

• Dysphagia (oesophageal extension) [24]
• Weight loss, fevers (invasive disease, malignancy)
• First presentation in young adult with no risk factors (test for HIV) [3,4]
• Non-healing lesions (exclude malignancy, especially chronic hyperplastic form) [23]

---

Common Mistakes

Clinical Mistakes

❌ Failing to investigate new-onset oral candidiasis in young adults: Always consider and test for HIV if no other obvious risk factor. [3,4]

❌ Missing oesophageal extension: Dysphagia or odynophagia indicates oesophageal involvement requiring higher-dose fluconazole (200-400 mg) and longer duration (14-21 days). [24]

❌ Not biopsying chronic hyperplastic candidiasis: This form has premalignant potential (5-15%); biopsy is mandatory to exclude dysplasia or carcinoma. [23]

❌ Using fluconazole in pregnancy: Fluconazole is teratogenic, especially at high doses/first trimester. Use topical therapy (nystatin, miconazole). [25]

❌ Ignoring denture hygiene in denture stomatitis: Antifungals alone will fail if denture biofilm is not addressed. Must combine treatment with overnight denture removal and disinfection. [12,13]

❌ Inadequate treatment duration: Stopping treatment when symptoms resolve (typically 2-3 days) leads to relapse. Treat for 7-14 days and continue 48 hours after symptom resolution. [1,5]

❌ Prescribing miconazole without checking drug interactions: Miconazole gel has significant systemic absorption and is a potent CYP3A4 inhibitor; avoid with warfarin (INR elevation), statins, certain antiretrovirals. [25]

Examination Mistakes

❌ Misdiagnosing oral lichen planus as candidiasis: Lichen planus has white reticular striae that CANNOT be scraped off; candidal plaques can be removed revealing erythematous base.

❌ Confusing geographic tongue with erythematous candidiasis: Geographic tongue is usually asymptomatic, has white borders, and changes pattern over days to weeks.

❌ Assuming all white oral lesions are thrush: Consider leukoplakia (cannot scrape off, requires biopsy), lichen planus, oral hairy leukoplakia (HIV), chemical burn, frictional keratosis.

Management Mistakes

❌ Using topical antifungals for oesophageal candidiasis: Topical therapy does not reach oesophageal mucosa; systemic fluconazole required. [24]

❌ Not considering fluconazole resistance in treatment failure: Especially in HIV/AIDS patients with recurrent disease or heavy prior azole exposure. Culture for speciation and susceptibility. [8,9]

❌ Continuing long-term fluconazole prophylaxis in HIV patients with immune reconstitution: Prophylaxis can be discontinued once CD4 \u003e200 for ≥3 months on ART. [11]

---

Model Answers

Q: Describe your approach to an HIV-positive patient with oral candidiasis and a CD4 count of 120 cells/μL.

Model Answer:

"This patient with HIV and a CD4 count of 120 cells/μL has significant immunosuppression, placing them at high risk for oral candidiasis and its complications.

Assessment: I would take a focused history including symptoms (oral discomfort, dysphagia, odynophagia, altered taste), duration, previous episodes, current ART regimen and adherence, and other opportunistic infections. On examination, I would classify the clinical form—pseudomembranous (scrapable white plaques), erythematous (red patches), or angular cheilitis. Importantly, I would assess for oropharyngeal extension and specifically ask about dysphagia, which would suggest oesophageal involvement requiring different management.

Investigations: In most cases, diagnosis is clinical. However, if atypical, treatment-refractory, or recurrent, I would send an oral swab for culture, species identification, and antifungal susceptibility testing to exclude azole-resistant non-albicans species such as C. glabrata or C. krusei.

Management:

• Acute treatment: Fluconazole 100-200 mg PO once daily for 7-14 days. If dysphagia is present suggesting oesophageal candidiasis, I would increase to 200-400 mg daily for 14-21 days.
• ART optimisation: Review current regimen and adherence; ensure viral suppression and CD4 recovery are on track. ART is the most important intervention for long-term prevention, reducing recurrence risk by 70-90%.
• Prophylaxis consideration: Given the CD4 count of 120, if this is their first episode, I would not start prophylaxis immediately. However, if recurrent (≥2 episodes per year), I would consider secondary prophylaxis with fluconazole 100-200 mg three times weekly or daily if CD4 \u003c50.
• Prophylaxis discontinuation criteria: Once CD4 count rises above 200 cells/μL for at least 3 months on ART, prophylaxis can be safely discontinued.
• Screening for other OIs: With CD4 \u003c200, ensure appropriate prophylaxis for Pneumocystis jirovecii pneumonia (co-trimoxazole) and consider screening for other opportunistic infections.

Follow-up: Review in 1-2 weeks to ensure clinical response. If refractory, send cultures and consider itraconazole solution, posaconazole, or even amphotericin/echinocandin if severe and resistant. Monitor CD4 count every 3-6 months and reassess prophylaxis need."

Q: A 72-year-old denture wearer presents with asymptomatic palatal redness. What is your diagnosis and management?

Model Answer:

"This presentation is consistent with denture stomatitis (chronic atrophic candidiasis), characterised by erythema confined to the denture-bearing area of the palate. It is caused by Candida biofilm formation on the denture fitting surface, often associated with continuous 24-hour denture wear and inadequate denture hygiene.

Assessment: I would ask about denture-wearing habits (day and night vs removing overnight), cleaning routine, age and fit of dentures, and any symptoms (usually asymptomatic but may have mild burning or altered taste). On examination, I would classify the extent of erythema (Newton classification: Type I—localised pinpoint, Type II—diffuse erythema, Type III—granular/papillary hyperplasia) and remove the dentures to inspect the fitting surface for debris and biofilm.

Management: This requires a combined approach of antifungal therapy and denture hygiene modification:

1. Antifungal treatment:

   • Topical: Miconazole oromucosal gel 2.5 mL QDS applied to palate AND to denture fitting surface for 14-28 days
   • OR Systemic: Fluconazole 50-100 mg once daily for 14 days if extensive or topical fails

2. Denture hygiene protocol (essential for cure and prevention of relapse):

   • Remove dentures overnight: Minimum 6-8 hours to allow mucosal recovery
   • Daily mechanical cleaning: Brush denture with denture brush and non-abrasive cleaner (not regular toothpaste which can abrade acrylic)
   • Overnight soaking: Soak in chlorhexidine 0.2% solution OR dilute sodium hypochlorite (1:80, e.g., Milton) for ≥8 hours to eliminate Candida biofilm. Chlorhexidine is preferred as it does not corrode metal clasps if partial denture.
   • Microwave disinfection (if available): 650W for 3 minutes in water bath as alternative

3. Denture review: Refer to dentist to assess denture fit and age. If dentures are old, ill-fitting, porous, or heavily colonised, replacement may be necessary.

Patient education: Explain that dentures are colonised with Candida biofilm, and antifungals alone will fail without proper hygiene. Emphasise overnight removal and daily disinfection as critical long-term measures.

Follow-up: Review at 2-4 weeks to ensure resolution. Recurrence occurs in 50-70% without ongoing hygiene measures."

---

References

1. Millsop JW, Fazel N. Oral candidiasis. Clin Dermatol. 2016;34(4):487-494. doi:10.1016/j.clindermatol.2016.02.022

2. Patil S, Rao RS, Majumdar B, Anil S. Clinical appearance of oral candida infection and therapeutic strategies. Front Microbiol. 2015;6:1391. doi:10.3389/fmicb.2015.01391

3. Patel PK, Erlandsen JE, Kirkpatrick WR, et al. The changing epidemiology of oropharyngeal candidiasis in patients with HIV/AIDS in the era of antiretroviral therapy. AIDS Res Treat. 2012;2012:262471. doi:10.1155/2012/262471

4. Thompson GR, Patel PK, Kirkpatrick WR, et al. Oropharyngeal candidiasis in the era of antiretroviral therapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010;109(4):488-495. doi:10.1016/j.tripleo.2009.11.026

5. Vila T, Sultan AS, Montelongo-Jauregui D, Jabra-Rizk MA. Oral Candidiasis: A disease of opportunity. J Fungi (Basel). 2020;6(1):15. doi:10.3390/jof6010015

6. Ramage G, Rajendran R, Sherry L, Williams C. Fungal biofilm resistance. Int J Microbiol. 2012;2012:528521. doi:10.1155/2012/528521

7. Mathé L, Van Dijck P. Recent insights into Candida albicans biofilm resistance mechanisms. Curr Genet. 2013;59(4):251-264. doi:10.1007/s00294-013-0400-3

8. Whaley SG, Berkow EL, Rybak JM, et al. Azole antifungal resistance in Candida albicans and emerging non-albicans Candida species. Front Microbiol. 2017;7:2173. doi:10.3389/fmicb.2016.02173

9. Cowen LE, Sanglard D, Howard SJ, Rogers PD, Perlin DS. Mechanisms of antifungal drug resistance. Cold Spring Harb Perspect Med. 2015;5(7):a019752. doi:10.1101/cshperspect.a019752

10. Akpan A, Morgan R. Oral candidiasis. Postgrad Med J. 2002;78(922):455-459. doi:10.1136/pmj.78.922.455

11. Panel on Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. Department of Health and Human Services. 2023. Available at: https://clinicalinfo.hiv.gov/en/guidelines

12. Gendreau L, Loewy ZG. Epidemiology and etiology of denture stomatitis. J Prosthodont. 2011;20(4):251-260. doi:10.1111/j.1532-849X.2011.00698.x

13. Emami E, Kabawat M, Rompré PH, Feine JS. Linking evidence to treatment for denture stomatitis: a meta-analysis of randomized controlled trials. J Dent. 2014;42(2):99-106. doi:10.1016/j.jdent.2013.11.021

14. Fukushima C, Matsuse H, Tomari S, et al. Oral candidiasis associated with inhaled corticosteroid use: comparison of fluticasone and beclomethasone. Ann Allergy Asthma Immunol. 2003;90(6):646-651. doi:10.1016/S1081-1206(10)61871-8

15. Hanania NA, Chapman KR, Kesten S. Adverse effects of inhaled corticosteroids. Am J Med. 1995;98(2):196-208. doi:10.1016/S0002-9343(99)80404-5

16. Samaranayake LP, Keung Leung W, Jin L. Oral mucosal fungal infections. Periodontol 2000. 2009;49:39-59. doi:10.1111/j.1600-0757.2008.00291.x

17. Lalla RV, Latortue MC, Hong CH, et al. A systematic review of oral fungal infections in patients receiving cancer therapy. Support Care Cancer. 2010;18(8):985-992. doi:10.1007/s00520-010-0892-z

18. Muzyka BC, Epifanio RN. Update on oral fungal infections. Dent Clin North Am. 2013;57(4):561-581. doi:10.1016/j.cden.2013.07.002

19. Sangeorzan JA, Bradley SF, He X, et al. Epidemiology of oral candidiasis in HIV-infected patients: colonization, infection, treatment, and emergence of fluconazole resistance. Am J Med. 1994;97(4):339-346. doi:10.1016/0002-9343(94)90300-x

20. Patton LL, Ramirez-Amador V, Anaya-Saavedra G, et al. Urban legends series: oral manifestations of HIV infection. Oral Dis. 2013;19(6):533-550. doi:10.1111/odi.12027

21. Moyes DL, Naglik JR. Mucosal immunity and Candida albicans infection. Clin Dev Immunol. 2011;2011:346307. doi:10.1155/2011/346307

22. Mayer FL, Wilson D, Hube B. Candida albicans pathogenicity mechanisms. Virulence. 2013;4(2):119-128. doi:10.4161/viru.22913

23. McCullough M, Jaber M, Barrett AW, et al. Oral yeast carriage correlates with presence of oral epithelial dysplasia. Oral Oncol. 2002;38(4):391-393. doi:10.1016/s1368-8375(01)00079-3

24. Pappas PG, Kauffman CA, Andes DR, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;62(4):e1-e50. doi:10.1093/cid/civ933

25. De Santis M, Di Gianantonio E, Cesari E, et al. First-trimester itraconazole exposure and pregnancy outcome: a prospective cohort study of women contacting teratology information services in Italy. Drug Saf. 2009;32(3):239-244. doi:10.2165/00002018-200932030-00006

26. Ishikawa KH, Mayer MP, Miyazima TY, et al. A multispecies probiotic reduces oral Candida colonization in denture wearers. J Prosthodont. 2015;24(3):194-199. doi:10.1111/jopr.12198

27. Pappas PG, Kauffman CA, Andes DR, et al. Executive summary: Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;62(4):409-417. doi:10.1093/cid/civ1194