Candida Vulvovaginitis

1. See also
   1. Vaginitis
2. Epidemiology
   1. Candida Vulvovaginitis accounts for 45% of Vaginitis
   2. Candida is cultured in 20-50% asymptomatic women
   3. Vaginitis often self diagnosed incorrectly
3. Etiology
   1. Acute: Candida albicans (90%)
      1. Normal commensal organism in vagina
      2. Infection when Corynebacterium suppressed
   2. Recurrent Vulvovaginal Candidiasis (4 or more episodes in a year)
      1. Candida glabrata (increasing Incidence, now 15%)
      2. Candida tropicalis
      3. Candida parapsilosis
      4. Candida krusei (responds to Topical Antifungals, but not to Fluconazole)
      5. Saccharomyces cerevisiae
4. Risk Factors
   1. Immunosuppression
      1. Diabetes Mellitus (esp. Uncontrolled)
      2. Depressed cell mediated Immunity (e.g. HIV or AIDS)
   2. Medications
      1. Corticosteroids
      2. Immunosuppressant Medications
      3. Broad spectrum antibiotics
      4. Oral Contraceptives
         1. Increases frequency of Candida carrier state
         2. Does not increase symptomatic Vulvovaginitis
   3. Heat and moisture retaining clothing (e.g. nylon)
   4. Pregnancy (and other hyperestrogenic states)
   5. Premenstrual phase of the Menstrual Cycle
   6. Obesity
5. Symptoms
   1. Asymptomatic in 20-50% of women
   2. Intense vaginal or Vulvar Pruritus (50% of cases)
   3. Vulvar Burning, soreness, or irritation
   4. Thick white curd-like or "cottage cheese" discharge
   5. No odor
   6. Dyspareunia
   7. Dysuria (33% of cases)
6. Signs
   1. Adherent white cottage-cheese discharge in vagina
      1. Sensitivity: 50%
      2. Specificity: 90%
   2. Vulvar erythema and edema (24% of cases)
7. Labs: Initial
   1. KOH Preparation (10%)
      1. Test Sensitivity: 50%
      2. Pseudohyphae or budding yeast forms
      3. 
   2. Vaginal pH <4.5 (Normal acidity)
   3. Absent Amine odor
   4. White Blood Cells not increased
   5. Wet-Prep is not sensitive or specific for yeast
      1. Bornstein (2001) Infect Dis Obstet Gynecol 9:105-11 [PubMed]
   6. Candida on Pap Smear
      1. Specific but very low Test Sensitivity
8. Labs: Complicated cases
   1. Indications: Complicated Vulvovaginal Candidiasis
      1. Recurrent candida Vaginitis (4 or more episodes in a year) OR
      2. Severe candida infections OR
      3. Immunocompromised patients (AIDS, poorly controlled Diabetes Mellitus)
   2. Fungal Culture positive
      1. Fungal Culture is rarely performed in typical cases (fungal PCR preferred)
      2. Fungal Culture may be very helpful in complicated cases
         1. Confirm asymptomatic carrier of vaginal Candida
         2. Identify cause of recurrent Vaginitis
   3. DNA probe or PCR for candida
      1. Consider in cases refractory to standard therapy
9. Differential Diagnosis (Consider for refractory cases)
   1. Other Vaginitis cause
      1. Bacterial Vaginosis
      2. TrichomonasVaginitis
   2. Infectious Cervicitis (Sexually Transmitted Disease)
   3. Allergic Vaginitis or Vulvitis
   4. Vulvodynia
   5. Herpes Simplex Virus
      1. HSV presents with unilateral painful lesions
      2. Contrast with bilateral, symmetric involvement in Candida Vulvovaginitis
10. Management: OTC Local First-Line Agents
    1. Precautions
       1. In pregnancy, limit to topical azole preparations (Miconazole, Clotrimazole) used for 7 days (lower concentrations)
    2. Miconazole (Monistat)
       1. Miconazole (Monistat-7) 2% cream PV qhs for 7 days
       2. Miconazole (Monistat-3) 4% cream, 5 g PV qhs for 3 days
       3. Miconazole Vag tabs 100mg PV qhs for 7 days
       4. Miconazole (Monistat-3) 200mg PV qhs for 3 days
       5. Miconazole 1200 mg vaginal tab PV qhs, 1 dose
    3. Clotrimazole (Gyn-Lotrimin, Mycelex G)
       1. Clotrimazole 1% cream qhs for 7 days
       2. Clotrimazole 2% cream qhs for 3 days
       3. Clotrimazole 200 mg vaginal tab PV qhs for 3 days
       4. Clotrimazole 100 mg vaginal tab PV qhs for 7 days
       5. Clotrimazole 500 mg vaginal tab PV qhs, 1 dose
    4. Terconazole (Newer, binds better to Candida)
       1. Vagistat-1 6.5% ointment, 5 g intravaginally once
          1. Highly effective and less irritating than creams
11. Management: Prescription Local First-Line Agents
    1. Butoconazole (Femstat)
       1. Mycelex-3 5g of 2% Cream PV QHS for 3 days
       2. Gynezole-1 (sustained release, bioadhesive) 5 g of 2% cream once intravaginally
    2. Terconazole (Newer, binds better to Candida)
       1. Terazol 80 mg vaginal suppository PV for 3 days
       2. Terazol-3 (0.8%) 5 g vaginal cream for 3 days
       3. Terazol-7 (0.4%) 5 g vaginal cream qhs for 7 days
    3. Nystatin
       1. Nystatin vaginal tablet (100,000 unit) PV daily for 14 days
       2. Nystatin ointment (100,000 units/g)
          1. Ointments are less irritating than creams
12. Management: Oral Agents
    1. Fluconazole 150 mg PO for 1 dose
       1. As effective as Clotrimazole PV
       2. Do not use in pregnancy
          1. Evidence of Miscarriage risk, with even 1-2 doses
          2. Mølgaard-Nielsen (2016) JAMA 315(1):58-67 +PMID:26746458 [PubMed]
       3. Consider repeat scheduled treatment for persistent symptoms
          1. Consider prescribing Fluconazole 150 mg every 3 days for up to 3 doses for persistent Vaginitis symptoms
       4. Symptom improvement delayed for 24 hours with Fluconazole
          1. Consider concurrently treating with Nystatin ointment (100,000 units) for the first several days (least irritating)
       5. Higher mycologic cure rates in the short term (NNT 30) and long term (NNT 19) compared with intravaginal agents
       6. References
          1. (1994) Med Lett Drugs Ther 36(631): 1-2 [PubMed]
          2. Denison (2020) Cochrane Database Syst Rev (8): CD002845 [PubMed]
    2. Brexafemme (Ibrexafungerp)
       1. Dosing: 150 mg tablet taken in 2 doses at 12 hours apart
       2. Consider in recurrent candida Yeast Vaginitis refractory to repeat Fluconazole dosing
       3. Cost is nearly 50 fold higher than generic Fluconazole (approxmately $500 for 2 doses)
       4. Marketed as fungicidal against yeast (in contrast to fungistatic azoles such as Fluconazole, Clotrimazole)
          1. However, in practice, first-line azoles are 80-90% effective for definitive resolution
       5. References
          1. (2021) Presc Lett 28(9): 49-50
13. Management: Recurrent or resistant Treatment
    1. Precautions
       1. Avoid treating asymptomatic carriers (may be normal flora in some patients)
       2. Consider risk factors above
    2. Any of above intravaginal meds for 14-21 days
       1. Consider maintenance after initial daily regimen
       2. Maintenance: Repeat application once weekly
          1. Consider using monthly at time of Menses
       3. Consider Terconazole (see above)
          1. More effective against other candida species
    3. Fluconazole (Diflucan)
       1. See below for maintenance protocol
       2. Less effective for non-albicans Candida
       3. Dose 1: 150 mg orally
       4. Dose 2: 150 mg PO at 72 hours after first dose
       5. Consider a 3rd dose at 72 hours after second
       6. Sobel (2001) Am J Obstet Gynecol 185:363-9 [PubMed]
    4. Other options (many with increased toxicity and risk)
       1. Ketoconazole (Nizoral) 200mg PO bid for 5-14 days
       2. Itraconazole (Sporanox) 200 mg PO qd for 3 days
       3. Gentian Violet vaginal staining 1-2x (Office charge)
       4. Boric Acid 600 mg vaginal tab bid for 14 days
          1. Use is controversial, but may be considered in refractory non-albicans candidal infection
          2. Sobel (2003) Am J Obstet Gynecol 189(5): 1297-1300 [PubMed]
       5. Flucytosine (Ancobon) cream applied to affected area
14. Management: Prophylaxis (more recent protocol)
    1. Indication
       1. Four or mor yeast infections per year
    2. Initial treatment
       1. Fluconazole (Diflucan) 150 mg PO q3 days for 3 doses
    3. Maintenance
       1. Fluconazole (Diflucan) 150 mg PO each week
       2. Monitor liver enzymes (consider q1-2 months)
    4. Efficacy
       1. Suppression while on treatment: 90%
       2. Following treatment: Infection recurs in 60%
    5. References
       1. Sobel (2004) N Engl J Med 351:876-83 [PubMed]
15. Management: Prophylaxis (old protocol)
    1. Protocol for 6 month maintenance regimen
       1. Start with 2 week recurrent treatment option above
       2. Follow treatment with prophylaxis option below
       3. Fungal Culture and exam timing
          1. Baseline
          2. Two weeks (after treatment regimen above)
          3. Three months
          4. Six months (when stopping prophylaxis)
    2. Medications
       1. Clotrimazole 500 mg vaginal tab weekly to montly
       2. Fluconazole 150 mg orally once weekly to monthly
       3. Miconazole 100 mg vaginal tab qhs twice weekly
       4. Avoid oral Ketoconazole due to hepatotoxicity
16. Prevention
    1. Control predisposing condition (e.g. Diabetes Mellitus)
    2. Reduce predisposing medications (e.g. Corticosteroid)
    3. Avoid moisture-retaining products near vagina
       1. Nylon underwear
       2. Panty-liners
       3. Vaginal Lubricants or Spermicides
    4. Lactobacillus (Probiotic) is not effective
       1. Does not prevent post-antibiotic Vaginitis
       2. Pirotta (2004) BMJ 329:548-51 [PubMed]
17. References
    1. Desai (1996) Am Fam Physician 54(4):1337-40 [PubMed]
    2. Hainer (2011) Am Fam Physician 83(7): 807-15 [PubMed]
    3. Nyirjesy (2001) Am Fam Physician 63(4):697-702 [PubMed]
    4. Paladine (2018) Am Fam Physician 97(5): 321-9 [PubMed]
    5. Sobel (1998) Am J Obstet Gynecol 178:203-11 [PubMed]
    6. Tobin (1995) Am Fam Physician 51(7):1715-20 [PubMed]