General practitioners are all too familiar with this condition, so there is little to be gained by reiterating common knowledge. There are, however, a few points worth making.
Although C. albicans is the commonest cause of vulvovaginal infection, other strains such as Candida (formerly Torulopsis) glabrata and Candida tropicalis, may also occasionally produce symptoms. C. glabrata is thought to account for about 5% of vaginal infections.
Accurate identification of Candida spp. is particularly important when dealing with persistent or recurrent infection; however, this identification may not be available routinely in all microbiology laboratories. Non-albicans strains of Candida often show partial or complete resistance to the commonly used topical and oral antifungal agents.
Oral antifungals (e.g. fluconazole, itraconazole) are extremely effective, easy to use and appear to be safe. They are, however, rather more expensive than topical treatments and should not be used in pregnancy.
5.1 RECURRENT CANDIDIASIS
A small number of women are plagued by frequent recurrences of vulvovaginal candidiasis. The reasons are unclear, although there is some evidence to suggest a localized Candida-specific defect in cell-mediated immunity. When a patient presents complaining of "recurrent thrush," one of the most important first steps in management is to make sure that the diagnosis is correct (see below).
5.1.1 Practical Points
Whenever possible try to send a vaginal swab for Candida culture on each occasion that symptoms are present. Failure to culture the yeast makes the diagnosis less likely.
If symptoms persist and Candida continues to be isolated after treatment, ask the laboratory to identify the Candida species and report on its sensitivities to the various antifungals. This will usually require the sample being sent to a reference laboratory. Non-albicans strains of Candida are often resistant to imidazoles (e.g. clotrimazole, miconazole, econazole) and triazoles (fluconazole, itraconazole) but may respond to topical nystatin (a polyene).
Consider a trial of an oral antifungal, such as fluconazole 150 mg stat followed by 50 mg daily for 1 week or itraconazole 200 mg bd for 1 day followed by 200 mg daily for 1 week. Lack of clinical response suggests that Candida is not the cause of the symptoms or that a resistant strain of Candida is present. Symptoms of vulval irritation, with or without discharge, which initially improve with antifungal treatment but then recur some days or weeks later are highly suggestive of candidiasis.
5.2 DIFFERENTIAL DIAGNOSES
5.2.1 Bacterial Vaginosis
Consider bacterial vaginosis in a woman with recurrent vaginal discharge that fails to respond to antifungal treatment. Vulval irritation is unusual in this condition.
5.2.2 Vulal Dermatoses (see Chapter 8)
A reasonable number of women with presumed persistent (rather than recurrent) "thrush" have been misdiagnosed and have a dermatosis. Vulval seborrheic dermatitis, lichen sclerosus, and lichen planus are not uncommon but any skin condition can affect the genitalia. Dermatoses often lose some of their characteristic features when affecting the vulval epithelium and a biopsy may be required to make the correct diagnosis. Some patients with a vulval dermatosis will have other body sites affected. In cases of contact dermatitis, there is often a history of allergy or a family history of atopy. Potential vulval sensitizing agents include topical medications (e.g. Tri-adcortyl, antifungal creams), KY jelly (propylene glycol sensitivity), spermicidal creams, sanitary pads, dyed lavatory paper, bubble-baths, and scented soaps (although prolonged soaking in a bath rather than fleeting contact with showering is required to produce a hypersensitivity reaction).
5.3 MANAGEMENT OF RECURRENT CANDIDIASIS
Once you are satisfied that the diagnosis is correct the following points are worth considering.
5.3.1 Prophylactic Antifungals
Women with peri-menstrual thrush may benefit from prophylactic antifungal therapy either before or just after the period. This can be as a single clotrimazole 500 mg pessary or fenticonazole 600 mg pessary, oral fluconazole 150 mg or itraconazole 200 mg bd for 1 day. Once monthly prophylaxis is insufficient for some women in which case try fortnightly or possibly weekly prophylaxis. This regimen should be continued for 3-6 months and then stopped and the situation reassessed.
5.3.2 Treatment of Male Sexual Partners
Treating the male partner with an antifungal cream does not reduce the frequency of recurrent episodes in the female. Men should therefore only receive treatment if they have evidence of candidal infection themselves (i.e. a balanitis or posthitis).
5.3.3 Treatment of the “Gut Reservoir”
Early studies suggested that recurrences of vaginal candidiasis result from reinfection from the gut. This is now considered unlikely and indeed more recent work has failed to show any benefit from the use of oral nystatin. Intestinal colonization by Candida therefore appears to play no role in recurrent vaginal infection and can be ignored.
5.3.4 “Deep-Seated” Vaginal Infection
Failure to eradicate Candida from the "deeper layers" of the vaginal mucosa has led some clinicians to suggest using longer courses of antifungal treatment. This is still an issue of debate, but consider treating acute recurrences with a 2-week course of antifungal pessaries or oral agents.
5.3.5 Diet
There is no evidence to suggest that a diet high in sugars or carbohydrates predisposes to thrush. One study of particular interest reported a reduction in vaginal Candida colonization among women ingesting 8 ounces of yoghurt daily. A "natural" yoghurt was used, supposedly containing Lactobacillus acidophilus. Although this work still requires confirmation with a larger number of patients and a placebo arm, yoghurt supplementation sounds attractive and would probably be well accepted. Interestingly, many of the so-called "live" or "natural" yoghurt products on the market do not contain Lactobacillus acidophilus or contain only "non-vaginal" strains of lactobacilli. A small number of studies
have shown an association between low zinc status and recurrent vaginal infection including recurrent candidiasis. This has led some clinicians to suggest a trial of oral zinc supplements for 1 or 2 months in women with particularly troublesome thrush. Garlic contains an antifungal, allicin, and has been advocated as a treatment for thrush; however, current evidence suggests that the amount of garlic required to provide clinically useful levels of allicin in the vagina may be socially unacceptable. Nevertheless, natural remedies are very fashionable and further study is certainly warranted.
5.3.6 Diabetes
Poorly controlled diabetes may predispose to thrush, but it is very uncommon to find diabetes in women with recurrent infection; however, it is prudent to dipstix the urine.
5.3.7 Oral Contraceptive Pill
Theoretical evidence suggests that the pill could play a role in potentiating vaginal candidiasis. A cytosol receptor for estrogen has been reported in C. albicans and certain hormones have been shown in vitro to stimulate yeast mycelial formation and hence virulence. In spite of this evidence, recent studies have failed to show an association between low-moderate dose oral contraceptive pill use and recurrent candidiasis.
5.3.8 Iron Deficiency Anemia
This does not predispose to recurrent thrush.
5.3.9 Bubble-Baths and Scented Soaps
The irritation associated with candidal vulvitis may be aggravated by bubble-baths and scented soaps. Conversely, epithelial damage due to a mild contact dermatitis to one of the chemicals in a bubble-bath or soap may predispose to symptomatic candidiasis.
5.3.10 Tight-Fitting Clothing
Women with recurrent thrush are often advised to avoid wearing nylon underwear and tights. The theory is that the increased humidity generated by the nylon may lead to mild epithelial maceration and subsequently lead to fungal invasion of the superficial tissue and hence to symptomatic infection. This is anecdotal but loose clothing does provide a degree of comfort to some women during recurrences.
5.3.11 Antibiotics
A number of women are prone to develop thrush during courses of oral antibiotics. This may be due to the elimination of the protective vaginal lactobacilli or to a direct potentiating effect on yeast growth. Prescribing a course of antifungals together with antibiotics is worth considering and is usually much appreciated by the patient.
5.3.12 Douches
Vinegar or sodium bicarbonate douches provide symptomatic relief for some women. It should be remembered that douching may facilitate the spread of lower genital tract bacteria into the uterus and is not to be generally recommended unless a screen for genital infection has been performed and proved negative.
5.3.13 Boric Acid
Gelatin capsules of boric acid have been successfully used to treat persistent vaginal candidiasis, in particular C. glabrata infection. The recommended dosage is 600 mg bd for two weeks and as the capsules are not generally available these need to be made up by a kindly pharmacist. As prolonged absorption of boric acid causes anorexia, vomiting, skin rash, and anemia, further study is required on the safety and efficacy of maintenance therapy.
5.3.14 Hormonal Therapy
There are anecdotal reports of successful treatments of persistent C. glabrata infection with progestogens, for example dydrogesterone or medroxyprogesterone acetate.
Summary of recurrent/persistent vaginal candidiasis
(1) Make sure that the diagnosis is correct. Dermatoses often present with vulval irritation.
(2) Identify the Candida spp. and check sensitivities to antifungals.
(3) Treat initially with a longer course of antifungals.
(4) Use monthly, fortnightly, or weekly oral or topical antifungals for 3-6 months as prophylaxis.
(5) No need to treat male partners with antifungals unless symptomatic (i.e. penile rash present).
The clinical and microscopic features of candidiasis are shown below (Figures 5.1-5.6). See also chapter 16 for candidiasis in men.
Figure 5.1(a). Vulvitis due to candidiasis
Figure 5.1(b). Perineal fissures due to candidiasis
Figure 5.2. Candidiasis - lumpy' white discharge
Figure 5.3. Candidiasis - vaginitis with a watery discharge
Figure 5.4. Gram stain of vaginal discharge due to candidiasis showing spores and pseudo-hyphae (lactobacilli also present)
Figure 5.5. Wet-mount preparation showing budding pseudo-hyphal strand
Figure 5.6. Gram stain of vaginal discharge due to Candida glabrata showing multiple spores without hyphae