Pathology of Recurrent Vulvovaginal Candidiasis
Definition and Epidemiology
Recurrent vulvovaginal candidiasis (RVVC) is defined as three or more symptomatic episodes within 12 months, affecting approximately 5-9% of women, with the highest prevalence in women aged 25-34 years. 1, 2
- The definition has evolved from the older criterion of four or more episodes per year to the current standard of three or more episodes 1
- RVVC affects an estimated 6 million women in the United States, causing approximately $4.7 billion in lost productivity annually 1
Pathophysiology and Mechanisms
Poorly Understood Host Factors
The pathogenesis of RVVC remains poorly understood, with most affected women having no apparent predisposing or underlying conditions. 1
- Possible contributing factors include genetic predisposition in idiopathic cases, drug resistance, and underdosing 1
- The mechanism by which asymptomatic Candida colonization converts to symptomatic disease is not fully elucidated 3
- Different pathogenic mechanisms may be operative in individual patients, resulting in a spectrum of clinical manifestations 3
Microbiological Considerations
Non-albicans Candida species, particularly C. glabrata, are found in 10-20% of RVVC cases and demonstrate reduced susceptibility to conventional azole therapies. 1
- C. glabrata does not form pseudohyphae or hyphae, making it difficult to recognize on microscopy 1
- Most RVVC cases are still caused by azole-susceptible C. albicans 2
pH-Dependent Drug Resistance
A critical but underrecognized factor is that all antifungal medications demonstrate significantly higher minimum inhibitory concentrations (MICs) at vaginal pH 4 compared to the laboratory standard pH 7. 1
- This pH effect differs by antifungal agent and yeast species 1
- Terconazole against C. glabrata shows the most dramatic difference, with MICs more than 388-fold higher at pH 4 than at pH 7 1
- Standard laboratory susceptibility testing at pH 7 underestimates clinically relevant azole resistance 2
Predisposing Factors
Identifiable Risk Factors
When present, the following conditions increase RVVC risk:
- Frequent antibiotic therapy disrupts normal vaginal flora 4
- Uncontrolled diabetes mellitus significantly impairs treatment response 1, 2
- Immunosuppression, including HIV infection (with colonization rates correlating with severity of immunodeficiency), corticosteroid use, or other debilitating medical conditions 1, 2
- Pregnancy, during which VVC occurs more frequently 1
- Contraceptive use has been associated with increased risk 4
- Sexual activity may play a role, though VVC is not typically sexually transmitted 4
Idiopathic Cases
The majority of women with RVVC do not have recognizable predisposing factors, representing a significant knowledge gap in understanding this condition. 1, 3
Clinical Impact and Morbidity
RVVC is associated with substantial morbidity beyond physical symptoms, including psychological distress, sexual dysfunction, and economic burden. 1
- Physical symptoms include itching, burning, swelling, discomfort, and vulvar erythema, edema, excoriation, and fissure formation 1
- Psychological effects include low self-esteem, loss of confidence, and challenges participating in regular activities 1
- Sexual and intimate life difficulties are common 1
- Missed work days compound the economic and psychological burden, creating a cycle of stress and anxiety 1
Treatment Response and Recurrence Patterns
Maintenance fluconazole therapy improves quality of life in 96% of women but is uncommonly curative, with more than 63% experiencing ongoing infections after completing maintenance therapy. 1