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Fungal Infections

Disease name and synonyms

Vaginal thrush, Candida vulvovaginitis, recurrent vulvovaginal candidiasis (candidosis) or  rVVC, chronic VVC (cVVC).

Fungi responsible (links to these)

Candida albicans (Candida glabrata following azole use, rarely other Candida species),

Disease description

As the  name indicates, vulvovaginal candidiasis can involve both the vagina and the vulva. More common symptoms are burning, itching, soreness and vaginal creamy discharge. Vulval examination shows erythema of the labia minora, majora, perineum often with oedema and fissuring. Sometimes perianal skin is affected. Examination of the vagina reveals erythema and/or adherent white/creamy discharge

Vulvovaginal candidosis (VVC) is mostly uncomplicated but it is regarded as complicated when there are  severe symptoms, recurrent episodes, during pregnancy, or colonisation with non-albicans Candida species or in immunocompromised patients. Recurrent vulvovaginal candidosis (rVVC) is defined as more than four confirmed episodes over 12 months. It affects some 5-9% of healthy women during their childbearing years, or those on hormone replacement therapy. Another group of women get cVVC, a recently recognised entity.

Frequency and global burden

Thrush is common. About 70% of all premenopausal women develop thrush at some point in their lives. By a mean age of 24 years, 60% of women had suffered at least one episode of vulvovaginal candidosis and 36% had at least one episode a year and 3% had it ‘almost all the time’.  Estimates suggest 135 million (8%) women get 4 or more attacks of vulvovaginal candidosis annually across the world.  In these patients there is often a worse response to initial treatment and a shorter time to relapse. There are no estimates of the frequency of cVVC, but is less common than rVVC.

Underlying problems and at risk patients

Certain conditions increase the incidence and possibly the severity of vulvovaginal candidosis, including pregnancy, antibiotic use, diabetes mellitus and cystic fibrosis.  HIV-seropositive women are not more likely to develop vaginal candidiasis than controls. Oestrogen status is important, accounting for post-menopausal women having rVVC on hormone replacement therapy (HRT). 

Other risk factors such as corticosteroid use and frequent antibiotic use should be identified. If sporadic risk factors can be identified prophylactic antifungal treatment can be used at the time. In many cases, however, the risk factors are persistent or cannot be identified.

Diagnostic testing

The vaginal pH is normal (3.8 to 4.5) in VVC, in contrast to bacterial vaginosis when it is higher than 4.5. Microbiological testing is important and almost always positive in acute episodes. Microscopy and culture of vaginal or vulval sample showing Candida. Some cultures may be positive in the absence of symptoms.

A small number of patients with acute episodes have negative cultures.

Recurrent VVC is diagnosed when 4 or more episodes occur over 12 months. Often these are diagnosed presumptively by responsiveness to antifungal treatment.  Cultures and microscopy may be negative, but it is important to exclude other causes of vulva discomfort and discharge.

Chronic VVC diagnostic criteria have recently been formulated (Hong et al, 2014 article). Highly distinctive features present for at least 3 months are: previous or current positive culture (or microscopy), exacerbation with antibiotics, discharge and marked improvement during menstruation. Other features commonly found, but not quite as specific include pain on intercourse, vulval soreness and vulval swelling. Discharge and itching are not distinctive features of cVVC. Most patients have a positive culture, but not all. They improve with antifungal therapy.

The most common differential diagnosis is bacterial vaginosis (BV) and patients may flip between VVC and BV. Other differential diagnoses include contact dermatitis to something applied intra-vaginally, desquamative inflammatory vaginitis, foreign body (usually a tampon), and others.

Rare instances of fluconazole resistance are seen in Candida albicans.

Treatments

There are numerous topical treatments, almost all are azoles such as clotrimazole. Azole drugs are not effective for C. glabrata and so this can be treated with nystatin pessaries, available in some countries. Also fluconazole should (not to be used in pregnancy -increased risk of cardiac defects in babies), a risk probably not associated with itraconazole.

The management of uncomplicated acute VVC consists of either topical or oral therapies, usually as a single dose of fluconazole 150mg, or 2 doses of 100mg itraconazole. In treatment-naïve patients all topical and oral azole therapies give an 80-95% clinical and mycological cure rate in non-pregnant women. Patients should be advised to avoid local irritants e.g. soaps, perfumed products and tight fitting synthetic clothing. Recurrent and cVVC respond to longer courses of daily treatment for 3- 6 months.

For C. glabrata and for resistant cases topical applications of boric acid gelatin capsule 600mg daily, inserted into the vagina, for 14 days, OR flucytosine cream - 5g /day for 14 days Sobel at al  or a mixture of flucytosine (1 g) and amphotericin B (100 mg) formulated in lubricating jelly base in a total 8 g delivered dose. White et al . Flucytosine cream is effective but is not widely available.

Outlook and prognosis

Most cases of thrush respond well to therapy and the interval between episodesis long. Recurrence may follow antibiotic use and sex. 

Recurrent use of azole antifungal agents can lead to colonisation with azole-resistant Candida. There are few alternative therapeutic agents available, namely nystatin and boric acid. The latter has been shown to have excellent efficacy but can only be prescribed by specialists from hospital pharmacies. When rVVC responds poorly to given treatment other causes for the symptoms need to be excluded and the patient referred.
Patients with rVVC must be followed-up regularly and samples for fungal culture, identification and susceptibility testing taken every 3 to 4 months. 

link: Differential diagnosis explained 

Image:

Vulvovaginal thrush

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