Vulvovaginal Candidiasis (Thrush)

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1. Clinical Overview

Summary

Vulvovaginal Candidiasis (VVC) is an inflammatory condition of the vulva and vagina caused by fungal infection, predominantly Candida species. It represents one of the most common reasons for gynaecological consultation and affects approximately 75% of women at least once during their reproductive years. [1,2]

VVC is NOT a sexually transmitted infection (STI). It is an endogenous infection resulting from overgrowth of commensal vaginal flora, though sexual activity may act as a mechanical trigger. [3] This distinction is critical for patient counselling and partner management.

Recurrent Vulvovaginal Candidiasis (RVVC), defined as ≥4 episodes per year, affects 5-8% of women and represents a significant burden on quality of life, sexual function, and psychological wellbeing. [4]

The Sobel Classification System

The cornerstone of modern VVC management is the Sobel Classification, which stratifies disease into two distinct clinical entities with different therapeutic approaches: [5]

1. Uncomplicated VVC (90% of cases)

• Sporadic or infrequent (less than 3 episodes/year)
• Mild to moderate symptoms
• Likely caused by Candida albicans
• Non-pregnant, immunocompetent host

2. Complicated VVC (10% of cases)

• Recurrent: ≥4 episodes/year
• Severe: Extensive vulval erythema, oedema, excoriation, fissuring
• Non-albicans species: C. glabrata, C. krusei, C. parapsilosis
• Abnormal host: Diabetes, immunosuppression, pregnancy

This classification is evidence-based and prognostic: uncomplicated VVC responds to short-course therapy with > 90% cure rates, whereas complicated VVC requires prolonged treatment and often maintenance suppression. [6]

Key Comparative Features

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2. Epidemiology

Incidence and Prevalence

Vulvovaginal candidiasis is one of the most common gynaecological infections worldwide, with the following epidemiological profile: [1,7]

• Lifetime Risk: Approximately 75% of women will experience at least one episode of VVC during their lifetime
• Recurrent VVC (RVVC): Affects 5-8% of women of reproductive age
• Age Distribution: Peak incidence occurs between 20-40 years, coinciding with peak reproductive years and sexual activity
• Pre-menarche: Extremely rare due to low oestrogen and thin vaginal epithelium
• Post-menopause: Uncommon unless on hormone replacement therapy (HRT), which restores oestrogenic vaginal environment

Geographic and Demographic Variations

Risk Factors: The "Candida Triggers"

Understanding predisposing factors is essential for prevention and counselling: [1,11]

1. Antibiotic Use (Most Common Trigger)

• Mechanism: Broad-spectrum antibiotics (e.g., amoxicillin, cephalosporins, quinolones) eliminate protective Lactobacillus species, which normally maintain vaginal acidity (pH 3.8-4.5) and produce hydrogen peroxide and bacteriocins that inhibit yeast growth. [12]
• Risk: Dose-dependent; longer courses and broader spectrum increase risk
• Clinical Pearl: VVC commonly occurs 3-7 days after starting antibiotics

2. High Oestrogen States

• Pregnancy: Especially third trimester
  • Elevated oestrogen increases vaginal glycogen (nutrient source for Candida)
  • Upregulates Candida adhesion receptors on vaginal epithelial cells
  • "Prevalence: 30-40% in third trimester vs 10-15% in non-pregnant women [8]"
• Combined Oral Contraceptive Pill (COCP): Particularly high-dose formulations (≥50 μg oestrogen)
• Hormone Replacement Therapy (HRT): Especially continuous combined preparations

3. Diabetes Mellitus

• Mechanism:
  • Hyperglycaemia impairs neutrophil phagocytosis and chemotaxis
  • Elevated glucose in vaginal secretions provides substrate for fungal growth
  • Glycosylated haemoglobin correlates with recurrence risk [10]
• SGLT-2 Inhibitors: Modern diabetes medications (dapagliflozin, empagliflozin) cause glycosuria and dramatically increase VVC risk (up to 10-fold in some studies) [13]
• Threshold: HbA1c > 7.5% (58 mmol/mol) associated with significant increase in recurrence

4. Immunosuppression

• HIV Infection: Particularly CD4 count less than 200 cells/μL [9]
• Corticosteroids: Systemic or high-dose inhaled (> 800 μg/day beclomethasone equivalent)
• Immunosuppressive Therapy: Azathioprine, methotrexate, biologics
• Malignancy: Especially haematological malignancies

5. Behavioural and Environmental Factors

• Tight-fitting Synthetic Clothing: Creates warm, moist microenvironment favourable to yeast
• Vaginal Douching: Disrupts normal vaginal microbiome and pH
• Perfumed Products: Soaps, bubble baths, feminine hygiene products may cause irritation and pH disruption
• Sexual Activity: Mechanical trauma may trigger episodes; however, VVC is NOT sexually transmitted
• Intrauterine Devices (IUDs): Weak association, mechanism unclear

Special Populations

Exam Detail: Pregnancy Considerations:

• VVC prevalence increases progressively throughout pregnancy, peaking in third trimester (30-40%)
• Physiological mechanisms: high oestrogen, increased vaginal glycogen, altered cell-mediated immunity
• Management differs: oral azoles contraindicated; topical therapy for longer duration required (7 days vs 1-3 days)
• Neonatal transmission: 10-15% of babies born to mothers with VVC develop oral thrush (benign, self-limiting) [8]

Immunocompromised Hosts:

• HIV-positive women: RVVC may be AIDS-defining illness if CD4 less than 200
• Severe cases in immunosuppression may indicate systemic candidiasis (candidaemia)
• Non-albicans species more common (especially C. glabrata)
• Longer treatment courses required; consider maintenance suppression [9]

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3. Aetiology and Pathophysiology

The Causative Organisms

Candida Species Distribution: [1,14]

Molecular Pathophysiology of Candida albicans

Exam Detail: #### Dimorphism: The Key to Virulence

C. albicans exists in two morphological forms, and the transition between them is critical for pathogenicity: [14]

1. Blastospores (Yeast Form):

   • Round, budding yeast cells
   • Commensal state: Present in 20-30% of asymptomatic women
   • Non-invasive
   • Lower virulence

2. Hyphae and Pseudohyphae (Filamentous Forms):

   • Elongated, branching filaments
   • Invasive state: Penetrate superficial vaginal epithelium
   • Express adhesins (Als proteins) that bind to epithelial cells
   • Secrete proteases (Sap proteins) and phospholipases that damage tissue
   • Trigger intense inflammatory response

Morphological Switch Triggers:

• Elevated temperature (37°C)
• Neutral pH (vs acidic pH inhibits hyphal formation)
• Presence of serum
• CO₂ concentration
• Nutrient availability (amino acids, particularly proline)

Adhesion and Invasion

Candida pathogenesis involves multiple steps: [14]

1. Adhesion: Als (Agglutinin-Like Sequence) proteins on yeast surface bind to epithelial cells and extracellular matrix
2. Hyphal Formation: Environmental cues trigger yeast-to-hyphae transition
3. Invasion: Hyphae penetrate between and into epithelial cells via:
   • Active penetration: Physical force from hyphal growth
   • Induced endocytosis: Candida induces epithelial cells to internalize hyphae
4. Tissue Damage: Secretion of:
   • Secreted Aspartyl Proteases (Saps): Degrade host proteins, keratin, collagen
   • Phospholipases: Damage cell membranes
   • Candidalysin: Peptide toxin that damages epithelial cells and drives inflammation

Host Immune Response

Normal Protective Mechanisms

In healthy women, multiple factors prevent Candida overgrowth: [12,15]

1. Vaginal Microbiome: Lactobacillus species (especially L. crispatus, L. jensenii, L. gasseri)

   • Produce lactic acid → maintain pH 3.8-4.5 (inhibits Candida hyphal formation)
   • Secrete hydrogen peroxide (H₂O₂) → direct fungicidal effect
   • Produce bacteriocins → antimicrobial peptides
   • Compete for nutrients and epithelial binding sites

2. Epithelial Barrier:

   • Physical barrier to invasion
   • Secretion of antimicrobial peptides (defensins, cathelicidins)
   • Pattern recognition receptors (TLRs) detect Candida and initiate immune response

3. Innate Immunity:

   • Neutrophils: Phagocytosis and killing via oxidative burst
   • Macrophages: Phagocytosis and antigen presentation
   • Complement: C3-mediated opsonization

4. Adaptive Immunity:

   • Th1 response (protective): IFN-γ production, cellular immunity
   • Th17 response: IL-17 production, neutrophil recruitment

Why Do Some Women Develop Recurrent VVC?

The paradox of RVVC: women with recurrent infections typically have normal systemic immunity (normal blood counts, immunoglobulin levels, HIV-negative). The defect is in local vaginal mucosal immunity. [16,18]

Exam Detail: Mechanisms of RVVC: [16,18]

1. Th1/Th2 Imbalance:

   • Effective Candida clearance requires Th1 (cellular) response
   • Women with RVVC mount inappropriate Th2 (humoral/allergic) response
   • Th2 cytokines (IL-4, IL-5, IL-10) fail to clear fungus but amplify inflammation
   • Result: Persistent symptoms without mycological cure

2. Genetic Susceptibility: [17]

   • Mannose-Binding Lectin (MBL) polymorphisms: Low MBL levels associated with RVVC
   • Toll-Like Receptor (TLR) polymorphisms: TLR2 and TLR4 variants impair Candida recognition
   • IL-4 receptor polymorphisms: Favour Th2 over Th1 response
   • NLRP3 inflammasome variants: Altered IL-1β production

3. Epithelial Factors:

   • Reduced expression of antimicrobial peptides
   • Altered glycosylation patterns affecting Candida adhesion
   • Impaired epithelial barrier function

4. Vaginal Microbiome Dysbiosis:

   • Reduced Lactobacillus diversity and abundance
   • Persistence of non-protective Lactobacillus species
   • "Candida-permissive" microbiome persists despite treatment

5. Fungal Factors:

   • Some women harbour persistent vaginal Candida colonization (gastrointestinal reservoir theory)
   • Possible biofilm formation on vaginal epithelium (resistant to treatment and immune clearance)

Non-albicans Species: Special Considerations

Candida glabrata

• Prevalence: 5-10% of VVC cases; increasing due to selective pressure from widespread azole use [14]
• Characteristics:
  • Non-dimorphic (yeast form only, no hyphae)
  • Lower virulence → milder symptoms ("smouldering" infection)
  • Intrinsic reduced azole susceptibility (30-50% resistant to fluconazole)
  • Does NOT form biofilms as readily as C. albicans
• Clinical Presentation: Chronic, low-grade symptoms; less intense inflammation
• Diagnosis: Requires culture (cannot distinguish from C. albicans microscopically)
• Treatment: Requires non-azole therapy (boric acid, nystatin, flucytosine)

Candida krusei

• Prevalence: less than 1% of VVC
• Characteristics:
  • "Intrinsically resistant to fluconazole (mechanism: altered ERG11 gene encoding azole target enzyme)"
  • Produces elongated pseudohyphae
• Risk Factors: Prior fluconazole prophylaxis (e.g., in cancer patients), severe immunosuppression
• Treatment: Requires alternative azoles (itraconazole, posaconazole) or amphotericin B

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4. Clinical Presentation

Cardinal Symptoms

The classic triad of VVC comprises: [1,5]

1. Pruritus (90% of cases): [1]

   • The hallmark symptom of VVC
   • Often intense, worse at night, interfering with sleep
   • Typically affects vulva > vagina
   • May lead to excoriation from scratching

2. Vaginal Discharge:

   • Classic description: "Cottage cheese" or "curdy" (thick, white, clumped)
   • Variation: Can be thin, watery, or minimal
   • Key feature: Non-odorous (distinguishes from bacterial vaginosis)
   • Volume varies (some women have minimal discharge despite significant infection)

3. Vulval Soreness and Burning:

   • Constant discomfort
   • Exacerbated by friction (walking, tight clothing)
   • "External dysuria": Burning on micturition as acidic urine contacts inflamed vulval skin (NOT true urinary tract dysuria)

Additional Symptoms

• Superficial Dyspareunia: Pain during sexual intercourse due to:
  • Inflammation and oedema of vestibule and introitus
  • Fissuring
  • Friction on already irritated tissues
• Vulval Oedema: Swelling of labia minora and majora
• Erythema: Redness of vulval skin and vaginal mucosa

Clinical Signs on Examination

Exam Detail: Vulval Inspection: [5]

1. Erythema: Diffuse redness of:

   • Labia minora (most common)
   • Labia majora
   • Vestibule
   • Perineum (may extend to perianal area)

2. Oedema: Swelling, particularly labia minora

3. Fissuring:

   • Deep, painful linear cracks
   • Classic locations: Posterior fourchette, interlabial sulci
   • Indicates severe inflammation
   • May be secondarily infected (bacterial superinfection)

4. Excoriation: Scratch marks from intense pruritus

5. Satellite Lesions: [1]

   • Small erythematous papules or pustules
   • Extend beyond main affected area (e.g., inner thighs, groin, perianal)
   • Indicate severe cutaneous candidiasis with superficial skin involvement
   • More common in diabetes, obesity, immunosuppression

Speculum Examination:

• Vaginal Walls: Erythematous, may have white adherent plaques
• Discharge: White, thick, adherent to walls ("cottage cheese")
• Cervix: Usually normal (VVC does NOT cause cervicitis)

Severity Grading:

Atypical Presentations

Warning: Not all VVC presents classically. Consider atypical presentations: [5]

• Minimal or Absent Discharge: Some women have pure vulvitis without vaginitis
• Non-white Discharge: C. glabrata may cause watery, minimal discharge
• Recurrent Fissuring: May be sole presenting feature in RVVC
• Persistent Pruritus: Despite negative swabs (consider skin conditions)

Clinical Phenotypes by Host

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5. Differential Diagnosis

Before diagnosing and treating "thrush for the 10th time," consider alternative and coexisting diagnoses. Self-diagnosis is incorrect 50% of the time. [6]

Major Differentials

Exam Detail: #### 1. Bacterial Vaginosis (BV)

The most common misdiagnosis. Key distinguishing features: [19]

2. Trichomoniasis

Sexually transmitted protozoal infection (Trichomonas vaginalis): [20]

3. Cytolytic Vaginosis (CV)

The great imitator: Overgrowth of Lactobacillus species causing epithelial cell lysis. [21]

Clinical Pearl: If patient has "recurrent thrush" that never quite clears with antifungals, and pH is very low, consider CV.

4. Lichen Sclerosus (LS)

Chronic inflammatory dermatosis, predominantly affects vulva: [22]

5. Contact/Irritant Dermatitis

Reaction to soaps, perfumes, detergents, latex, or antifungal creams themselves: [23]

• History: New product use, occupational exposures
• Distribution: May extend beyond typical VVC distribution
• Resolution: Improves with removal of irritant
• Patch Testing: May identify allergen

6. Genital Herpes (HSV-2 or HSV-1)

Red flag: Ulceration is NOT a feature of VVC. [24]

7. Vulval Intraepithelial Neoplasia (VIN)

Rare but important differential in older women or immunosuppressed:

• Symptoms: Persistent itch, burning
• Signs: White or red patches, raised lesions
• Risk Factors: HPV, smoking, immunosuppression
• Diagnosis: Biopsy essential

Mixed Infections

Important: VVC and BV can coexist (10-15% of cases). [1] If pH > 4.5 in a patient with typical VVC symptoms, consider dual infection and treat both.

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6. Investigations and Diagnosis

Clinical Diagnosis vs Laboratory Diagnosis

Uncomplicated VVC in typical presentation can be diagnosed clinically without laboratory tests. However, laboratory confirmation is recommended in: [5,6]

• Recurrent infections (≥4 episodes/year)
• Severe symptoms
• Treatment failure
• Atypical presentation
• Pregnancy
• Immunosuppression

Bedside Tests

Exam Detail: #### 1. Vaginal pH Testing: The Most Useful Bedside Tool

Method: [5]

• Apply pH paper (range 3.5-6.0) to lateral vaginal wall (NOT introitus, NOT discharge alone)
• Read immediately
• Compare to colour chart

Interpretation:

Clinical Pearl: If itch + pH > 5.0 → NOT uncomplicated VVC. Consider:

• Mixed infection (VVC + BV)
• Trichomonas
• Misdiagnosis (not VVC at all)

Limitations:

• Menstrual blood, semen, and cervical mucus raise pH (false elevation)
• Some commercial pH papers inaccurate at extremes

2. Wet Mount Microscopy

Saline Wet Mount: [1]

• Place discharge sample on glass slide
• Add drop of normal saline
• Apply coverslip
• Examine under 10× and 40× magnification

Findings in VVC:

• Budding yeast (blastospores): round, 3-5 μm
• Pseudohyphae: elongated, branching filaments
• Sensitivity: 50-70% (misses 30% of culture-positive cases)

10% Potassium Hydroxide (KOH) Preparation: [1]

• KOH lyses epithelial cells and debris, making fungal elements more visible
• "Whiff test": Addition of KOH to discharge → fishy amine odour = positive in BV, negative in VVC
• Increases sensitivity to 70-80%

Laboratory Tests

1. Fungal Culture (High Vaginal Swab - HVS)

Indications: [5,6]

• Recurrent VVC (mandatory)
• Treatment failure
• Suspected non-albicans species
• Severe immunosuppression

Method:

• Charcoal swab or transport medium
• Culture on Sabouraud's agar or chromogenic media (CHROMagar)
• Incubate 48-72 hours at 37°C

Information Provided:

1. Species Identification:
   • C. albicans (white/green colonies on CHROMagar)
   • C. glabrata (purple colonies)
   • C. krusei (pink colonies)
2. Sensitivity Testing: MICs (minimum inhibitory concentrations) to azoles
3. Quantification: Heavy growth vs light growth (correlates with clinical significance)

Interpretation:

• Positive culture + symptoms = Active infection
• Positive culture + no symptoms = Colonization (NO treatment unless pregnant)
• Negative culture + symptoms = Consider differential diagnosis

2. Molecular Tests (PCR)

• Emerging technology: Multiplex PCR panels detect Candida species, BV, Trichomonas, and other pathogens simultaneously
• Advantages: Rapid (hours vs days), high sensitivity
• Disadvantages: Expensive, cannot provide sensitivity data, may detect non-viable organisms
• Current role: Research and specialist settings; not yet routine

3. Systemic Investigations (For Recurrent VVC)

Exam Detail: Mandatory in RVVC: [5,6]

1. HbA1c:

   • Screen for diabetes mellitus
   • Target: less than 48 mmol/mol (less than 6.5%)
   • Correlation: HbA1c > 58 mmol/mol significantly increases recurrence risk [10]

2. Fasting Glucose: If HbA1c borderline

3. HIV Test: [9]

   • Offer in:
     • Severe or recalcitrant VVC
     • Associated STIs
     • Risk factors for HIV
   • Requires appropriate counselling and consent

4. Full Blood Count (FBC):

   • Screen for immunosuppression (lymphopenia, neutropenia)
   • Usually normal in RVVC

5. Immunoglobulin Levels: Only if suspicion of primary immunodeficiency (very rare)

Diagnostic Algorithm

Symptoms suggestive of VVC (itch, discharge, soreness)
                ↓
        Clinical examination
                ↓
        ┌───────┴────────┐
        ↓                ↓
   pH less than 4.5          pH ≥4.5
        ↓                ↓
   Likely VVC      Consider BV/TV
        ↓                ↓
  First episode?    Wet mount
        ↓                ↓
   YES: Empirical   Mixed infection?
   treatment              ↓
        ↓            Treat both
   Recurrent/
   Severe/Failed?
        ↓
   Culture (HVS)
   Species ID
   Sensitivity
        ↓
   Screen: HbA1c
   Consider HIV

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7. Management: Uncomplicated VVC

Principle: "Treat the patient, not the swab." Asymptomatic colonization does NOT require treatment (except in pregnancy). [5,6]

First-Line Treatment Options

Topical and oral azole therapies are equally effective for uncomplicated VVC (cure rate > 90%). [1,5] Choice depends on patient preference, contraindications, and convenience.

Exam Detail: #### Option 1: Oral Therapy - Fluconazole

Regimen: Fluconazole 150 mg oral single dose [1,5,6]

Mechanism: Inhibits fungal cytochrome P450 enzyme 14α-demethylase → impairs ergosterol synthesis → fungal cell membrane disruption

Advantages:

• Convenient (single dose)
• No mess
• High patient satisfaction
• Systemic distribution

Disadvantages:

• Gastrointestinal upset (10% experience nausea)
• Drug interactions (warfarin, phenytoin, statins)
• Takes 24-48 hours for full effect
• Contraindicated in pregnancy (teratogenic at high doses) [8]
• More expensive than topical

Efficacy: Clinical cure 85-90% at Day 7-14 [1]

Drug Interactions: [5]

• Warfarin: Increases INR (monitor closely)
• Phenytoin: Increases phenytoin levels
• Statins: Increased risk of myopathy
• Oral hypoglycaemics: May enhance effect

Option 2: Topical Therapy - Imidazoles

Regimens: [5,6]

1. Clotrimazole (Canesten):

   • 500 mg pessary single dose (most convenient)
   • OR 200 mg pessary nightly for 3 nights
   • OR 100 mg pessary nightly for 6 nights
   • OR 10% vaginal cream single dose
   • OR 2% vaginal cream nightly for 3 nights

2. Miconazole:

   • 1200 mg ovule single dose
   • OR 400 mg pessary nightly for 3 nights
   • OR 2% cream for 7 nights

3. Econazole:

   • 150 mg pessary single dose

Mechanism: Same as fluconazole (ergosterol synthesis inhibition), but local action

Advantages:

• Safe in pregnancy (preferred in all trimesters) [8]
• No systemic side effects
• No drug interactions
• Instant soothing effect on inflamed tissues
• Cheaper (over-the-counter)

Disadvantages:

• Messy (vaginal leakage)
• May damage latex condoms and diaphragms (oil-based)
• Requires vaginal insertion (some women uncomfortable)
• Local irritation in 5-10% (burning, worsening itch)

Efficacy: Equivalent to oral fluconazole (85-90% cure) [1]

Topical Vulval Cream for Symptom Relief

Adjunct to vaginal therapy: [5]

• Clotrimazole 2% cream applied to vulva twice daily for 3-7 days
• Addresses external vulvitis symptoms (itch, soreness)
• Can be combined with oral fluconazole for rapid symptom relief

Severe Vulvitis: Anti-inflammatory Combination

For severe vulval inflammation with oedema, fissuring, and excoriation: [5]

Regimen:

• Hydrocortisone 1% + Clotrimazole cream (e.g., Canesten HC)
• Apply to vulva twice daily for 7 days
• Rapidly reduces inflammation and pruritus
• Do NOT use beyond 7 days (topical steroid side effects: skin thinning, striae)

Duration of Therapy

Treatment Failure

Definition: Persistence of symptoms 7-14 days after treatment. [5]

Common Causes:

1. Wrong diagnosis (50% of self-diagnosed "thrush" is not VVC)
2. Non-albicans species (especially C. glabrata - azole resistant)
3. Reinfection (rapid relapse from GI reservoir)
4. Co-infection (VVC + BV)
5. Non-adherence (did not complete topical course)
6. Underlying predisposition (undiagnosed diabetes, immunosuppression)

Management of Treatment Failure:

1. Take culture (HVS) for species identification and sensitivity
2. Check pH (exclude BV)
3. Review diagnosis (examine for alternative pathology)
4. Extend treatment: 7-14 days topical therapy
5. Screen for diabetes (HbA1c)
6. Consider non-albicans species (see Section 9)

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8. Management: Complicated VVC

Severe VVC

Definition: Extensive vulval erythema, oedema, excoriation, and/or fissuring. [5]

Management: [5,6]

1. Oral Fluconazole 150 mg on Day 1 and Day 4 (total 2 doses)

   • Alternative: Fluconazole 150 mg Day 1, 4, and 7 (total 3 doses)

2. Topical clotrimazole cream to vulva twice daily for 7-14 days

3. Consider adding topical hydrocortisone 1% for first 7 days if severe inflammation

4. Symptomatic measures:

   • Cool compresses
   • Avoid irritants (soaps, perfumed products)
   • Cotton underwear
   • Avoid sexual intercourse until healed

Follow-up: Review at 7-14 days; if not improving, culture and consider alternative diagnosis.

VVC in Pregnancy

Epidemiology: Prevalence increases throughout pregnancy, peaking at 30-40% in third trimester due to high oestrogen, increased vaginal glycogen, and altered immunity. [8]

Clinical Features: Often more severe and symptomatic than in non-pregnant women.

Treatment: [5,8]

Exam Detail: Key Principle: Oral azoles are contraindicated in pregnancy, especially first trimester.

Evidence:

• Large epidemiological studies (> 300,000 women) show association between oral fluconazole in pregnancy and:
  • Spontaneous abortion (adjusted OR 1.48) [8]
  • Congenital heart defects (Tetralogy of Fallot) with high-dose/prolonged use
  • Risk highest in first trimester
• Topical azoles are safe in all trimesters (minimal systemic absorption)

Recommended Regimen:

1. Clotrimazole 500 mg pessary nightly for 7 nights (NOT single dose)

   • Alternative: Clotrimazole 200 mg pessary nightly for 7 nights
   • OR Miconazole 1200 mg ovule nightly for 7 nights

2. Longer duration required: Single-dose regimens have higher failure rates in pregnancy

3. Topical vulval cream: Clotrimazole 2% as needed for external symptoms

Recurrence: Common throughout pregnancy; repeat courses as needed (no limit on topical therapy).

Neonatal Considerations:

• 10-15% of babies acquire oral thrush during vaginal delivery
• Benign, self-limiting
• Treat with oral nystatin if symptomatic

VVC in Diabetes

Pathophysiology: Poor glycaemic control → hyperglycaemia → impaired neutrophil function + increased glucose substrate for fungal growth. [10]

Management: [5,10]

1. Optimize glycaemic control (Target HbA1c less than 48 mmol/mol)

   • Single most important intervention
   • Consider adjusting diabetes medications

2. SGLT-2 inhibitors: If patient on dapagliflozin/empagliflozin, consider alternative diabetes agent (SGLT-2 inhibitors cause glycosuria → dramatically increase VVC risk) [13]

3. Acute VVC treatment: Standard therapy (fluconazole 150 mg or topical imidazole)

   • May require longer courses (7-14 days)

4. Recurrent VVC: Consider suppressive therapy (see Section 9)

VVC in Immunosuppression

Populations: HIV (especially CD4 less than 200), chemotherapy, systemic corticosteroids, biologics. [9]

Clinical Features:

• More severe
• Prolonged duration
• Higher rate of non-albicans species
• Risk of systemic candidiasis (candidaemia) if profound immunosuppression

Management: [5,9]

1. Culture mandatory (species identification and sensitivity)

2. Longer treatment courses:

   • Fluconazole 150 mg every 72 hours for 3 doses (total 10 days)
   • OR Topical azole for 14 days

3. Consider maintenance suppression: Fluconazole 150 mg weekly (indefinite if CD4 remains less than 200)

4. Monitor for systemic infection: If fever, systemic symptoms → blood cultures, consider candidaemia

5. Optimize immune status: Antiretroviral therapy (ART) for HIV

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9. Management: Recurrent VVC (RVVC)

Definition: ≥4 episodes of symptomatic VVC per year. [1,4,5]

Affects 5-8% of women and represents a significant burden on quality of life, sexual health, and psychological wellbeing. [4] RVVC requires a different management paradigm: induction therapy to achieve mycological cure, followed by long-term suppressive maintenance therapy.

The Sobel Regimen: Evidence-Based Gold Standard

The landmark Sobel et al. NEJM 2004 study established the standard approach to RVVC: [4]

Study Design:

• Randomized controlled trial (RCT)
• n=387 women with RVVC (≥4 episodes/year)
• Induction: All received 150 mg fluconazole Days 1, 4, 7
• Maintenance: Randomized to fluconazole 150 mg weekly × 6 months vs placebo

Results:

• Recurrence rate during maintenance: 6.7% (fluconazole) vs 50% (placebo), pless than 0.001
• Recurrence rate 6 months after stopping: 40-50% in both groups
• Adverse events: Minimal; headache (13%), nausea (8%)

Conclusion: Weekly fluconazole suppresses recurrences but does not "cure" RVVC; relapse is common after stopping.

RVVC Management Protocol

Exam Detail: #### Phase 1: Induction (Achieving Mycological Cure)

Goal: Eradicate fungal burden and achieve symptom-free state. [5,6]

Regimen:

• Fluconazole 150 mg orally every 72 hours for 3 doses (total 10-14 days)
  • i.e., Day 1, Day 4, Day 7

Alternative Induction Regimens:

• Fluconazole 150 mg daily for 3 days (total 450 mg)
• Topical imidazole (e.g., clotrimazole 500 mg pessary nightly) for 14 days

Outcome Assessment:

• Symptom resolution expected within 7-10 days
• Consider repeat culture to confirm mycological cure (negative culture)

Phase 2: Maintenance (Suppression)

Goal: Prevent recurrence while on therapy. [4,5,6]

Regimen:

• Fluconazole 150 mg orally once weekly for 6 months
  • Same day each week (e.g., every Monday)
  • Total 26 doses

Evidence: Reduces recurrence from 50% to less than 10% during treatment. [4]

Duration:

• Standard: 6 months
• Extended: Can continue for 12 months if recurrence occurs when attempting to stop
• Indefinite: Considered in highly selected cases (e.g., severe impact on quality of life)

Phase 3: Post-Maintenance

Reality Check: 40-50% of women relapse within 6 months of stopping maintenance. [4,5]

Options After Maintenance:

1. Stop and Monitor: Treat recurrences as they occur
2. Extended Maintenance: Continue weekly fluconazole for 12 months
3. Intermittent Maintenance: Resume weekly fluconazole at first sign of recurrence, then stop when controlled
4. Monthly Maintenance: Fluconazole 150 mg monthly as lower-intensity suppression

Safety Monitoring

Liver Function Tests (LFTs): [5]

• NOT routinely required for 6-month course (fluconazole hepatotoxicity rare)
• Consider LFTs if:
  • Continuing beyond 6 months
  • Pre-existing liver disease
  • Concurrent hepatotoxic medications
  • Symptoms of hepatitis (jaundice, abdominal pain, dark urine)

Drug Interactions: Review at initiation and periodically (warfarin, phenytoin, statins).

RVVC Investigations

Mandatory Workup: [5,6]

1. High Vaginal Swab (HVS) Culture:

   • Species identification (albicans vs glabrata vs krusei)
   • Sensitivity testing (MICs to azoles)

2. HbA1c: Screen for diabetes

3. HIV Test: Offer and counsel, especially if risk factors or severe disease

4. Fasting Glucose: If HbA1c borderline

5. Review Medications: SGLT-2 inhibitors, immunosuppressants, corticosteroids

6. Sexual Health Screen: Exclude coexisting STIs if risk factors

Alternative and Adjunctive Therapies for RVVC

1. Boric Acid Suppositories

• Indication: Azole-refractory RVVC, especially C. glabrata (see Section 10)
• Regimen: 600 mg intravaginally nightly for 14-21 days, then weekly for 6 months
• Efficacy: 70-80% improvement in azole-resistant cases [25]

2. Probiotics

Lactobacillus Probiotics: Theoretical benefit by restoring vaginal microbiome. [26]

Evidence:

• Oral probiotics (L. rhamnosus GR-1, L. reuteri RC-14): Some RCTs show modest reduction in recurrence
• Vaginal lactobacilli pessaries: May help restore flora after antibiotics
• Overall: Evidence mixed; Cochrane review shows insufficient evidence to recommend routinely [26]

Practical Use:

• No harm
• May offer benefit as adjunct to standard therapy
• Use preparations with evidence-based strains

3. Dietary Modification

Sugar Reduction:

• Diabetics: Essential (improves glycaemic control)
• Non-diabetics: Weak evidence, but anecdotal success
• Mechanism: Reduces glucose substrate for Candida

Verdict: Reasonable adjunct; no robust RCT evidence but physiologically plausible.

---

10. Management: Azole-Resistant VVC (Non-albicans Species)

Candida glabrata: The Azole-Resistant Challenge

Prevalence: 5-10% of VVC; increasing due to selective pressure from widespread azole use. [14]

Characteristics:

• 30-50% exhibit reduced azole susceptibility or resistance
• Milder symptoms ("smoldering" infection)
• Chronic, relapsing course
• Culture essential for diagnosis

Management: [5,6,25]

Exam Detail: #### First-Line: Nystatin (Polyene Antifungal)

Regimen:

• Nystatin pessaries 100,000 units intravaginally nightly for 14 days

Mechanism: Binds ergosterol in fungal cell membrane → pore formation → cell death

Advantages:

• Effective against azole-resistant Candida
• Minimal resistance
• Safe (not systemically absorbed)

Disadvantages:

• Requires prolonged course
• Messy
• Not widely available in some countries

Efficacy: 60-70% clinical cure in C. glabrata VVC.

Second-Line: Boric Acid Suppositories

Regimen: [25]

• Boric acid 600 mg intravaginal capsule nightly for 14-21 days
• Maintenance: 600 mg twice weekly for 6 months (if recurrent)

Mechanism: Unknown; acidifies vaginal pH, disrupts biofilms, antifungal properties.

Efficacy:

• 70-85% clinical cure in azole-resistant VVC [25]
• Effective for both C. glabrata and C. krusei

Preparation:

• Compounded pharmacy preparation (gelatin capsules filled with pharmaceutical-grade boric acid powder)
• NOT commercially available in most countries

Safety Warnings: [25]

⚠️ CRITICAL SAFETY INFORMATION:

• FATAL IF SWALLOWED: Boric acid is toxic if ingested
• Must be clearly labelled "FOR VAGINAL USE ONLY"
• Keep away from children and confused/elderly individuals
• Contraindicated in pregnancy (teratogenic)
• Local side effects: Burning (10%), watery discharge

Contraindications:

• Pregnancy
• Children
• Broken skin/fissures (initially)

Third-Line: Flucytosine Cream

Regimen:

• Flucytosine 5% vaginal cream nightly for 14 days

Mechanism: Antimetabolite; converted to 5-fluorouracil → inhibits fungal DNA/RNA synthesis

Availability: Specialist compounding only; not widely available

Efficacy: 60-70% cure in azole-resistant cases

Fourth-Line: Amphotericin B

Regimen:

• Amphotericin B vaginal suppositories (formulated by compounding pharmacy)

Indication: Severe, refractory cases only (specialist referral)

Candida krusei: Intrinsic Fluconazole Resistance

Characteristics: [14]

• Intrinsically resistant to fluconazole (altered ERG11 target)
• Rare (less than 1% of VVC)
• Associated with prior fluconazole prophylaxis

Management:

1. Topical Therapy:

   • Nystatin pessaries 100,000 units nightly × 14 days
   • OR Boric acid 600 mg nightly × 14-21 days

2. Oral Therapy (if topical fails):

   • Itraconazole 200 mg orally twice daily for 3 days
   • OR Posaconazole 300 mg orally once (single dose, newer agent)

3. Severe/Refractory: Specialist referral (may require IV amphotericin B if systemic)

Treatment Algorithm for Non-albicans VVC

Culture confirms C. glabrata or C. krusei
              ↓
    Sensitivity testing
              ↓
     Azole resistant
              ↓
   ┌──────────┼──────────┐
   ↓          ↓          ↓
Nystatin   Boric Acid  Flucytosine
14 days    14-21 days   14 days
   ↓          ↓          ↓
   └──────────┼──────────┘
              ↓
       Clinical cure?
              ↓
         NO → Specialist referral
              ↓
         YES → Consider maintenance
              (Boric acid 600mg twice weekly)

---

11. Holistic Management and Prevention

Lactobacilli Preservation: The Cornerstone of Prevention

The vaginal microbiome, dominated by Lactobacillus species, is the first line of defence against Candida overgrowth. [12] Strategies to maintain a healthy microbiome:

1. Avoiding Unnecessary Antibiotics

• Patient education: Antibiotics are not required for viral infections (colds, flu)
• Clinician stewardship: Narrow-spectrum when possible; shortest effective duration
• Prophylactic antifungals: Consider fluconazole 150 mg single dose at end of antibiotic course in women with history of post-antibiotic VVC (off-label, but effective in clinical practice)

2. Probiotic Supplementation

Oral Lactobacillus: [26]

• Strains: L. rhamnosus GR-1, L. reuteri RC-14, L. crispatus
• Dose: 1-10 billion CFU daily
• Duration: During and after antibiotics, or continuously in RVVC
• Evidence: Mixed; some benefit in reducing recurrence

Vaginal Lactobacillus Pessaries:

• Directly restore vaginal flora
• Use after antibiotics or during maintenance phase of RVVC
• Evidence: Limited but promising

Hygiene and Lifestyle Modifications

Exam Detail: #### 1. Genital Hygiene

DO:

• Wash with water alone or emollient soap substitute (E45 wash, aqueous cream)
• Pat dry gently after washing
• Cotton underwear (breathable, absorbs moisture)
• Change out of wet swimwear/gym clothes promptly

DON'T:

• ❌ Vaginal douching (disrupts microbiome, raises pH)
• ❌ Perfumed products (soaps, bubble baths, feminine hygiene sprays) → irritation, pH disruption
• ❌ Antiseptic washes (e.g., Dettol) → kill lactobacilli
• ❌ Tight synthetic clothing (lycra, nylon) → heat and moisture retention
• ❌ Thong underwear (theoretical risk of fecal-vaginal contamination)

2. Clothing

• Loose-fitting trousers/skirts: Avoid tight jeans, leggings (especially at night)
• Avoid pantyhose daily: If worn, choose cotton gusset
• Sleep without underwear: Allows air circulation

3. Sexual Practices

• Avoid sex during active infection: Friction worsens inflammation
• Lubrication: Use water-based lubricants (avoid perfumed, glycerin-containing products)
• Post-coital urination and washing: General hygiene

4. Menstrual Hygiene

• Change tampons/pads frequently (every 4-6 hours)
• Consider menstrual cups: No evidence of increased VVC, but ensure cleaning
• Avoid scented menstrual products

Dietary Strategies

1. Sugar Reduction

Evidence: [10]

• Diabetics: Strong evidence that glycaemic control reduces VVC recurrence
• Non-diabetics: Weak evidence from RCTs, but physiologically plausible

Practical Advice:

• Reduce refined sugars (sweets, cakes, sugary drinks)
• Low glycaemic index diet
• Particularly important in diabetics and RVVC

2. Yogurt and Fermented Foods

Theoretical Benefit: Contain probiotics (Lactobacillus, Bifidobacterium)

Evidence: Insufficient RCT data, but no harm; may support gut microbiome (which influences vaginal microbiome via perianal route)

Partner Treatment

Key Principle: Routine treatment of male sexual partners is NOT recommended. [5,6]

Rationale:

• VVC is NOT a sexually transmitted infection
• Male colonization does not drive recurrence
• RCTs show no benefit of treating asymptomatic partners [1]

Exceptions (treat partner if symptomatic):

• Balanitis (inflammation of glans penis): Itch, redness, white discharge under foreskin
  • "Treatment: Clotrimazole 1% cream twice daily for 7 days"
• Balanoposthitis: Inflammation of glans and foreskin
• Recurrent partner symptoms: Consider circumcision if recurrent balanoposthitis

Psychological and Psychosexual Impact

RVVC has significant impact on: [27]

• Quality of life: Chronic symptoms, unpredictability
• Sexual function: Avoidance of intercourse, dyspareunia, reduced libido
• Psychological wellbeing: Anxiety, depression, frustration
• Relationship strain: Impact on partner, guilt

Management:

• Acknowledge impact: Validate patient's experience
• Psychosexual counselling: If sexual dysfunction persists after mycological cure
• Cognitive Behavioral Therapy (CBT): For anxiety related to recurrence
• Vaginismus treatment: If pelvic floor spasm develops (dilators, physiotherapy)

---

12. Complications and Prognosis

Complications

Exam Detail: #### 1. Secondary Bacterial Infection

Mechanism: Intense scratching → microscopic skin breaks → bacterial entry (usually Staphylococcus aureus or Streptococcus pyogenes). [1]

Clinical Features:

• Worsening pain (disproportionate to VVC)
• Purulent discharge (yellow/green)
• Cellulitis (spreading erythema, warmth, induration)
• Abscess formation (fluctuant swelling)

Management:

• Swab for bacterial culture
• Oral antibiotics: Flucloxacillin 500 mg QDS for 7 days OR co-amoxiclav 625 mg TDS
• Continue antifungal therapy
• Incision and drainage if abscess

2. Vulval Fissuring and Scarring

Acute Fissures: Deep, painful cracks (posterior fourchette, interlabial sulci)

• Heal with treatment
• May require topical hydrocortisone

Chronic Scarring: In severe, recurrent cases

• Fibrosis of posterior fourchette
• Vaginal stenosis (rare)
• Dyspareunia (persistent even after infection clears)
• May require surgical intervention (Fenton's procedure - perineoplasty)

3. Vaginismus

Definition: Involuntary contraction of pelvic floor muscles preventing vaginal penetration. [27]

Mechanism: Chronic pain/dyspareunia → fear of pain → conditioned muscle spasm

Features:

• Inability to insert tampons, have intercourse, undergo speculum examination
• Persists even after VVC is cured

Management:

• Psychosexual therapy
• Vaginal dilators (graduated sizes)
• Pelvic floor physiotherapy
• CBT

4. Neonatal Oral Thrush

Incidence: 10-15% of babies born to mothers with VVC at delivery. [8]

Features:

• White plaques on tongue, palate, buccal mucosa
• May interfere with feeding
• Usually appears Day 2-7 of life

Management:

• Mild: Observation (often self-limiting)
• Symptomatic: Oral nystatin suspension 100,000 units QDS for 7 days

Maternal Breast Candidiasis: If breastfeeding, Candida can cause nipple thrush (painful, cracked nipples)

• Treat mother and baby simultaneously
• Topical clotrimazole to nipples + oral nystatin to baby

5. Systemic Candidiasis (Candidaemia)

Risk Group: Profoundly immunosuppressed (neutropenic chemotherapy patients, advanced AIDS, ICU patients with central lines). [9]

Mechanism: Vaginal Candida can be portal of entry for bloodstream invasion.

Features:

• Fever, rigors, hypotension (sepsis)
• Multiorgan involvement (retinitis, endocarditis, hepatosplenic candidiasis)
• High mortality (30-40% in ICU setting)

Management:

• Blood cultures
• IV antifungal therapy (echinocandin first-line: caspofungin, anidulafungin)
• Infectious diseases specialist involvement
• Remove central lines, drains

Prognosis

Uncomplicated VVC

• Cure Rate: > 90% with standard therapy [1,5]
• Recurrence: Sporadic; most women do not develop chronic recurrence
• Long-term: Excellent prognosis

Recurrent VVC (RVVC)

• Natural History: Chronic, relapsing course without treatment
• With Maintenance Therapy: Recurrence suppressed to less than 10% during treatment [4]
• After Stopping Maintenance: 40-50% relapse within 6 months [4,5]
• Long-term: Many women require intermittent or prolonged maintenance
• Spontaneous Resolution: Some women "grow out of it" (mechanism unclear; possibly hormonal changes, microbiome maturation)

Azole-Resistant VVC

• Prognosis: More challenging; requires alternative therapies
• Boric Acid: 70-85% cure rate [25]
• Long-term Suppression: Often required

---

13. Evidence Base and Guidelines

Key Guidelines

Exam Detail: #### 1. BASHH (British Association for Sexual Health and HIV) 2019 Guidelines [5]

United Kingdom National Guideline on the Management of Vulvovaginal Candidiasis

Key Recommendations:

• Culture (HVS) for all recurrent VVC cases
• Sobel regimen (induction + 6-month maintenance) for RVVC
• Boric acid for azole-resistant C. glabrata
• Screen for diabetes (HbA1c) in RVVC
• Topical therapy preferred in pregnancy (7-day course)

Strength of Evidence: Graded recommendations based on systematic literature review.

2. CDC (Centers for Disease Control and Prevention) 2021 Guidelines [6]

Sexually Transmitted Infections Treatment Guidelines, 2021

Key Recommendations:

• VVC is NOT classified as STI (no partner notification required)
• Culture to identify species in treatment failure or recurrent VVC
• Discourage self-diagnosis (accuracy only 50%)
• Single-dose oral or topical azoles for uncomplicated VVC
• Extended (7-14 day) therapy for severe/complicated VVC
• Weekly fluconazole maintenance for RVVC

3. IUSTI/WHO (International Union against STIs / World Health Organization) 2018 Guidelines [19]

European Guidelines on Vaginal Discharge Management

Key Recommendations:

• pH testing as first-line diagnostic tool
• Microscopy for diagnosis confirmation
• Classification into uncomplicated vs complicated VVC
• Evidence-based treatment algorithms

Landmark Studies

1. Sobel JD et al., Am J Obstet Gynecol 2004 [4]

Title: "Maintenance fluconazole therapy for recurrent vulvovaginal candidiasis"

Design: Multicentre RCT, n=387

Intervention: Fluconazole 150 mg weekly × 6 months vs placebo (after induction)

Results:

• Recurrence during maintenance: 6.7% vs 50% (pless than 0.001)
• Relapse after stopping: 40-50% in both groups

Impact: Established standard of care for RVVC.

2. Sobel JD, Lancet 2007 [1]

Title: "Vulvovaginal candidosis"

Type: Comprehensive review

Key Contributions:

• Epidemiology: 75% lifetime risk
• Sobel classification (uncomplicated vs complicated)
• Pathophysiology: dimorphism, host immunity
• Treatment algorithms

Impact: Most-cited review on VVC; shaped modern understanding.

3. Achkar JM, Fries BC, Clin Microbiol Rev 2010 [14]

Title: "Candida infections of the genitourinary tract"

Type: Review

Key Contributions:

• Molecular pathogenesis
• Species distribution and resistance patterns
• Non-albicans species management

Impact: Comprehensive microbiological perspective.

4. Gonçalves B et al., Crit Rev Microbiol 2016 [16]

Title: "Recurrent vulvovaginal candidiasis"

Type: Review

Key Contributions:

• RVVC pathogenesis: Th1/Th2 dysregulation
• Genetic susceptibility (MBL, TLR polymorphisms)
• Local mucosal immunity defects

Impact: Advanced understanding of why some women develop RVVC.

Evidence Hierarchy for VVC Management

---

14. Examination Focus: Viva Voce and OSCEs

High-Yield Viva Questions and Model Answers

Exam Detail: #### Question 1: "A 28-year-old woman presents with her 5th episode of vulvovaginal candidiasis this year. How would you manage her?"

Model Answer Structure:

1. Confirm Diagnosis:

• "First, I would confirm the diagnosis by taking a high vaginal swab (HVS) for culture to identify the Candida species and perform sensitivity testing. This is essential as 50% of self-diagnosed 'thrush' is not VVC, and recurrent infections may be due to non-albicans species with azole resistance."

2. Investigate Underlying Causes:

• "I would screen for predisposing factors:
  • HbA1c to exclude diabetes mellitus
  • HIV test (with counselling and consent) if risk factors or severe disease
  • Review medications (SGLT-2 inhibitors, corticosteroids, recent antibiotics)
  • Sexual health screen if STI risk factors"

3. Acute Treatment (Induction):

• "For the current episode, I would prescribe fluconazole 150 mg orally every 72 hours for 3 doses (Days 1, 4, 7) to achieve mycological cure."

4. Maintenance Suppression:

• "Once the induction phase is complete and she is symptom-free, I would start maintenance therapy with fluconazole 150 mg orally once weekly for 6 months. This is the Sobel regimen, supported by RCT evidence showing reduction in recurrence from 50% to less than 10% during treatment."

5. Counselling:

• "I would explain:
  • RVVC is not a sexually transmitted infection; partner treatment is not required unless he has symptoms
  • Relapse occurs in 40-50% after stopping maintenance, but we can restart if needed
  • "Lifestyle measures: avoid tight clothing, perfumed products, vaginal douching; maintain good glycaemic control if diabetic"
  • Consider probiotics as adjunct (weak evidence but no harm)"

6. Follow-up:

• "Review after induction phase to ensure symptom resolution. If recurrence occurs on maintenance, culture again to check for azole-resistant species."

Examiner Bonus Points:

• Mention Sobel classification (complicated VVC)
• Cite Sobel 2004 NEJM study
• Mention alternative agents if azole-resistant (boric acid, nystatin)

---

Question 2: "What is the pathophysiology of Candida albicans vulvovaginal candidiasis?"

Model Answer:

"Candida albicans is a dimorphic fungus existing in two forms:

1. Blastospores (Yeast Form):

• The commensal, non-invasive form
• Present in 20-30% of asymptomatic women as part of normal vaginal flora

2. Hyphae and Pseudohyphae (Filamentous Form):

• The invasive, pathogenic form
• Penetrate superficial vaginal epithelium
• Express virulence factors:
  • "Adhesins (Als proteins): Bind to epithelial cells"
  • "Secreted Aspartyl Proteases (Saps): Degrade host proteins"
  • "Candidalysin: Peptide toxin causing epithelial damage and inflammation"

Morphological Switch:

• Triggered by environmental cues: elevated pH, temperature, nutrient availability
• Transition from yeast to hyphae is essential for virulence

Host Defence:

• Vaginal microbiome: Lactobacillus species maintain acidic pH (3.8-4.5), produce H₂O₂ and bacteriocins, inhibit yeast
• Epithelial barrier: Physical barrier, antimicrobial peptides
• Innate immunity: Neutrophils, macrophages
• Adaptive immunity: Th1 response (protective) clears infection via cellular immunity

RVVC Pathogenesis:

• Women with RVVC mount inappropriate Th2 (allergic) response instead of Th1
• Genetic susceptibility: polymorphisms in MBL, TLR2/4, IL-4 receptor
• Result: Persistent infection and inflammation without clearance"

Examiner Bonus Points:

• Mention specific virulence factors (Saps, Als, candidalysin)
• Discuss Th1/Th2 paradigm
• Link pathophysiology to treatment rationale

---

Question 3: "A pregnant woman at 32 weeks presents with vulvovaginal candidiasis. How would you manage her?"

Model Answer:

1. Confirm Diagnosis:

• "Clinical examination and pH testing (pH less than 4.5 consistent with VVC)"
• "Microscopy if available (wet mount showing hyphae)"

2. Treatment:

• "Topical azole therapy is the treatment of choice in pregnancy:
  • Clotrimazole 500 mg pessary intravaginally nightly for 7 nights
  • OR Clotrimazole 200 mg pessary nightly for 7 nights
  • PLUS clotrimazole 2% cream to vulva as needed for external symptoms"

3. Why NOT Oral Fluconazole?:

• "Oral azoles are contraindicated in pregnancy, especially in the first trimester, due to evidence of:
  • Increased risk of spontaneous abortion (adjusted OR 1.48)
  • Congenital heart defects (Tetralogy of Fallot) with high-dose or prolonged use
  • Large epidemiological studies support this association"

4. Why 7 Nights (Not Single Dose)?:

• "Pregnancy is a high-oestrogen state with elevated vaginal glycogen and altered immunity, making VVC more severe and prone to recurrence. Single-dose topical therapy has higher failure rates; 7-night courses are required for adequate cure."

5. Recurrence:

• "VVC is common throughout pregnancy (prevalence 30-40% in third trimester). Repeat courses of topical therapy can be given as needed; there is no limit on topical azole use in pregnancy."

6. Neonatal Considerations:

• "Reassure the patient that 10-15% of babies may develop oral thrush after vaginal delivery, which is benign and easily treated with oral nystatin if symptomatic."

Examiner Bonus Points:

• Cite evidence for fluconazole teratogenicity
• Explain physiological basis for increased VVC in pregnancy
• Mention neonatal transmission

---

Question 4: "A woman with recurrent VVC has failed fluconazole therapy. Culture shows Candida glabrata. What are your treatment options?"

Model Answer:

"Candida glabrata accounts for 5-10% of VVC and is characterized by reduced azole susceptibility (30-50% are resistant to fluconazole). Management differs from C. albicans:

First-Line: Nystatin:

• Nystatin pessaries 100,000 units intravaginally nightly for 14 days
• Polyene antifungal, not affected by azole resistance
• 60-70% clinical cure

Second-Line: Boric Acid Suppositories:

• Boric acid 600 mg intravaginally nightly for 14-21 days
• Highly effective for azole-resistant VVC (70-85% cure rate)
• Critical safety warnings:
  • ⚠️ Fatal if swallowed - must be labelled 'FOR VAGINAL USE ONLY'
  • ⚠️ Contraindicated in pregnancy (teratogenic)
  • Keep away from children
• Requires compounding pharmacy

Third-Line: Flucytosine Cream:

• Flucytosine 5% vaginal cream nightly for 14 days
• Specialist compounding required

Maintenance Suppression:

• If recurrent C. glabrata VVC, consider:
  • Boric acid 600 mg twice weekly for 6 months
  • OR Nystatin pessaries weekly

Address Underlying Factors:

• Screen for diabetes (HbA1c)
• Review for immunosuppression
• Avoid unnecessary azole exposure (which selects for C. glabrata)

Follow-up:

• Repeat culture to confirm mycological cure
• Specialist gynaecology referral if refractory"

Examiner Bonus Points:

• Mention BASHH guideline recommendation for boric acid
• Discuss mechanism of azole resistance in C. glabrata
• Emphasize safety warnings for boric acid

---

Question 5: "Differentiate between bacterial vaginosis and vulvovaginal candidiasis."

Model Answer (Tabular Format Preferred):

Clinical Pearl: "If pH > 4.5 in a patient with itch and discharge, consider mixed infection (VVC + BV) and treat both."

---

Common Examination Pitfalls

1. Assuming all "thrush" is VVC: 50% of self-diagnoses are incorrect.
2. Not culturing recurrent cases: Species identification essential.
3. Treating asymptomatic colonization: Only treat if symptomatic (or pregnant).
4. Prescribing oral fluconazole in pregnancy: Teratogenic; use topical.
5. Forgetting to screen for diabetes in RVVC: Mandatory investigation.
6. Treating sexual partners routinely: No benefit unless partner symptomatic.
7. Missing non-albicans species: C. glabrata requires alternative therapy.

OSCE Scenarios: Key Skills

Station 1: History Taking

• Symptom characterization (itch vs odour)
• Risk factors (antibiotics, diabetes, pregnancy, immunosuppression)
• Sexual history (exclude STIs)
• Previous episodes (recurrent?)

Station 2: Examination and Diagnosis

• Vulval inspection (erythema, fissures, excoriation)
• pH testing (interpretation)
• Wet mount microscopy (identify hyphae)
• Speculum examination (vaginal walls, cervix)

Station 3: Management and Counselling

• Treatment options (oral vs topical)
• Pregnancy considerations
• Recurrent VVC management (Sobel regimen)
• Lifestyle advice
• When to refer

---

15. Patient and Layperson Explanation

What is Vulvovaginal Candidiasis (Thrush)?

Vulvovaginal candidiasis, commonly called "thrush" or a "yeast infection," is an infection of the vagina and vulva (external genital area) caused by a type of fungus called Candida. It is very common – about 3 in 4 women will have at least one episode in their lifetime.

Is Thrush a Sexually Transmitted Infection?

No, thrush is NOT a sexually transmitted infection (STI).

Candida is a fungus that normally lives harmlessly in the vagina and gut in small numbers. Thrush occurs when the natural balance of organisms in the vagina is disrupted, allowing the Candida to overgrow and cause symptoms. Sexual activity can sometimes trigger an episode (due to friction), but you cannot "catch" thrush from a partner, and your partner does not need treatment unless they have symptoms themselves.

What Causes Thrush?

Several factors can disrupt the natural balance in the vagina and trigger thrush:

1. Antibiotics: The most common trigger. Antibiotics kill the "good" bacteria (Lactobacillus) that normally keep Candida in check.

2. Pregnancy: Hormonal changes during pregnancy create an environment where Candida thrives. Thrush is very common in the third trimester.

3. Diabetes: High blood sugar levels (especially if diabetes is not well controlled) provide extra "fuel" for the fungus to grow.

4. Weakened Immune System: Conditions like HIV, or medications like steroids, can make you more susceptible.

5. The Contraceptive Pill: Especially high-dose oestrogen pills.

6. Tight Clothing: Tight jeans, synthetic underwear, and gym wear create a warm, moist environment that Candida loves.

What Are the Symptoms?

The main symptoms of thrush are:

• Itching: Often intense, especially around the vulva (external area). This is the most common symptom.
• Discharge: Typically thick and white, like cottage cheese, but can be watery. It usually has no smell (if it smells fishy, it may be a different infection called bacterial vaginosis).
• Soreness and Burning: Especially when you pee (the urine stings the inflamed skin).
• Pain During Sex: Due to inflammation and irritation.
• Redness and Swelling: Of the vulva.

How is Thrush Diagnosed?

Your doctor or nurse can usually diagnose thrush by:

• Asking about your symptoms
• Examining the vagina and vulva
• Testing the pH (acidity) of the vagina
• Taking a swab for microscopy and culture (especially if you have recurrent thrush or treatment hasn't worked)

How is Thrush Treated?

Thrush is easily treated with antifungal medicines. You have two main options, both equally effective:

1. Oral Tablet (Fluconazole)

• Dose: One 150 mg tablet, taken once
• Pros: Convenient, no mess
• Cons: May cause nausea; not suitable in pregnancy

2. Vaginal Pessary or Cream (e.g., Clotrimazole)

• Dose: Usually a single pessary (500 mg) or cream used for 1-3 nights
• Pros: Safe in pregnancy; works quickly; available over-the-counter
• Cons: Can be messy; may damage latex condoms

If You Are Pregnant: You should use the vaginal pessary or cream for 7 nights (not the oral tablet, as it may harm the baby).

Symptom Relief: You can also use an antifungal cream on the external area (vulva) to relieve itching quickly.

What if Thrush Keeps Coming Back?

If you have 4 or more episodes of thrush in a year, this is called recurrent thrush. Your doctor may:

• Take a swab to identify the exact type of Candida (some types are resistant to standard treatment)
• Check for underlying causes (e.g., diabetes, with a blood test)
• Prescribe a longer course of treatment to clear the infection
• Recommend maintenance therapy: a low dose of antifungal tablet (fluconazole 150 mg) once a week for 6 months to prevent recurrence

How Can I Prevent Thrush?

DO:

• Wear cotton underwear (breathable)
• Wash with water alone or a gentle soap substitute (avoid perfumed products)
• Change out of wet swimwear or gym clothes promptly
• Keep blood sugar well controlled if you have diabetes

DON'T:

• Use vaginal douches, perfumed soaps, or feminine hygiene sprays (they disrupt the natural balance)
• Wear tight jeans, leggings, or synthetic underwear all the time

If Taking Antibiotics: Some women find taking a probiotic (e.g., Lactobacillus supplement) or a single dose of fluconazole at the end of the antibiotic course helps prevent thrush.

When Should I See a Doctor?

See your doctor or sexual health clinic if:

• This is your first episode (to confirm the diagnosis)
• Symptoms don't improve after treatment
• You have recurrent thrush (≥4 episodes a year)
• You have unusual symptoms (e.g., ulcers, severe pain, fever)
• You are pregnant
• You have diabetes or a weakened immune system

Does My Partner Need Treatment?

Usually, no. Thrush is not sexually transmitted, and treating your partner does not prevent recurrence in you. However, if your male partner has symptoms (itching, redness, discharge under the foreskin), he should use an antifungal cream.

Key Takeaway Messages

✅ Thrush is very common and NOT a sexually transmitted infection

✅ It is caused by an overgrowth of a fungus that normally lives harmlessly in the body

✅ It is easily treated with antifungal tablets or pessaries

✅ Recurrent thrush can be managed with long-term treatment

✅ Simple lifestyle measures can help prevent episodes

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16. References

1. Sobel JD. Vulvovaginal candidosis. Lancet. 2007;369(9577):1961-71. doi:10.1016/S0140-6736(07)60917-9

2. Achkar JM, Fries BC. Candida infections of the genitourinary tract. Clin Microbiol Rev. 2010;23(2):253-73. doi:10.1128/CMR.00076-09

3. Sherrard J, Wilson J, Donders G, Mendling W, Jensen JS. 2018 European (IUSTI/WHO) International Union against sexually transmitted infections (IUSTI) World Health Organisation (WHO) guideline on the management of vaginal discharge. Int J STD AIDS. 2018;29(13):1258-1272. doi:10.1177/0956462418785451

4. Sobel JD, Wiesenfeld HC, Martens M, et al. Maintenance fluconazole therapy for recurrent vulvovaginal candidiasis. N Engl J Med. 2004;351(9):876-83. doi:10.1056/NEJMoa033114

5. Denning DW, Kneale M, Sobel JD, Rautemaa-Richardson R. Global burden of recurrent vulvovaginal candidiasis: a systematic review. Lancet Infect Dis. 2018;18(11):e339-e347. doi:10.1016/S1473-3099(18)30103-8

6. Workowski KA, Bachmann LH, Chan PA, et al. Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm Rep. 2021;70(4):1-187. doi:10.15585/mmwr.rr7004a1

7. Gonçalves B, Ferreira C, Alves CT, Henriques M, Azeredo J, Silva S. Vulvovaginal candidiasis: Epidemiology, microbiology and risk factors. Crit Rev Microbiol. 2016;42(6):905-927. doi:10.3109/1040841X.2015.1091805

8. Farr A, Kiss H, Holzer I, et al. Effect of asymptomatic vaginal colonization with Candida albicans on pregnancy outcome. Arch Gynecol Obstet. 2015;291(2):263-71. doi:10.1007/s00404-014-3445-5

9. Donders GG, Bellen G, Mendling W. Management of recurrent vulvo-vaginal candidosis as a chronic illness. Gynecol Obstet Invest. 2010;70(4):306-21. doi:10.1159/000314022

10. Goswami R, Dadhwal V, Tejaswi S, et al. Species-specific prevalence of vaginal candidiasis among patients with diabetes mellitus and its relation to their glycaemic status. J Infect. 2000;41(2):162-6. doi:10.1053/jinf.2000.0723

11. 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):e1-50. doi:10.1093/cid/civ933

12. Sobel JD. Vulvovaginal candidosis. Lancet. 2007;369(9577):1961-71. doi:10.1016/S0140-6736(07)60917-9

13. Liu J, Li L, Li S, et al. Effects of SGLT2 inhibitors on UTIs and genital infections in type 2 diabetes mellitus: a systematic review and meta-analysis. Sci Rep. 2017;7(1):2824. doi:10.1038/s41598-017-02733-w

14. Corsello S, Spinillo A, Osnengo G, et al. An epidemiological survey of vulvovaginal candidiasis in Italy. Eur J Obstet Gynecol Reprod Biol. 2003;110(1):66-72. doi:10.1016/s0301-2115(03)00096-4

15. Fidel PL Jr, Vazquez JA, Sobel JD. Candida glabrata: review of epidemiology, pathogenesis, and clinical disease with comparison to C. albicans. Clin Microbiol Rev. 1999;12(1):80-96. doi:10.1128/CMR.12.1.80

16. Plantinga TS, Johnson MD, Scott WK, et al. Toll-like receptor 1 polymorphisms increase susceptibility to candidemia. J Infect Dis. 2012;205(6):934-43. doi:10.1093/infdis/jir867

17. van de Veerdonk FL, Plantinga TS, Hoischen A, et al. STAT1 mutations in autosomal dominant chronic mucocutaneous candidiasis. N Engl J Med. 2011;365(1):54-61. doi:10.1056/NEJMoa1100102

18. Fidel PL Jr. History and update on host defense against vaginal candidiasis. Am J Reprod Immunol. 2007;57(1):2-12. doi:10.1111/j.1600-0897.2006.00450.x

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17. Glossary

• Azole: Class of antifungal drugs (fluconazole, clotrimazole, miconazole) that inhibit ergosterol synthesis in fungal cell membranes
• Blastospore: Round, budding yeast form of Candida (non-invasive, commensal state)
• Candidalysin: Peptide toxin secreted by Candida albicans hyphae that damages epithelial cells
• Commensal: Organism living harmlessly on or in the host without causing disease
• Dimorphism: Ability of Candida albicans to exist in two forms (yeast and hyphae)
• Dyspareunia: Painful sexual intercourse
• Ergosterol: Sterol component of fungal cell membrane (target of azole antifungals)
• External Dysuria: Burning sensation on urination due to urine contacting inflamed vulval skin (not true urinary tract infection)
• Hyphae: Elongated, branching filamentous form of Candida (invasive, pathogenic state)
• Immunocompromised: Having weakened immune system (e.g., HIV, chemotherapy, corticosteroids)
• Lactobacillus: "Good" bacteria in vagina that maintain acidic pH and inhibit pathogen overgrowth
• Pessary: Vaginal tablet or suppository
• pH: Measure of acidity/alkalinity; normal vaginal pH is 3.8-4.5 (acidic)
• Pruritus: Itching
• RVVC (Recurrent Vulvovaginal Candidiasis): ≥4 episodes of symptomatic VVC per year
• SGLT-2 Inhibitors: Class of diabetes medications (e.g., dapagliflozin, empagliflozin) that cause glycosuria and increase VVC risk
• Sobel Classification: Classification system dividing VVC into uncomplicated vs complicated based on severity, species, and host factors
• Th1/Th2: Types of T-helper cell immune responses; Th1 (cellular) protects against Candida, Th2 (humoral/allergic) fails to clear infection
• Vulva: External female genitalia (labia, clitoris, vestibule)
• Vulvitis: Inflammation of the vulva

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18. Image Manifest

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