Fortnightly Review: Management of genital candidiasisBMJ 1995; 310 doi: https://doi.org/10.1136/bmj.310.6989.1241 (Published 13 May 1995) Cite this as: BMJ 1995;310:1241
- D W Denning
- Correspondence to: Dr D W Denning, Department of Infectious Diseases and Tropical Medicine (Monsall Unit), North Manchester General Hospital, Manchester M8 5RB.
Vaginal candidiasis affects about 75% of women, 40-50% having recurrent episodes
Pruritus vulvae and vaginal discharge are the cardinal symptoms
Candida albicans accounts for about 90% of infections and C glabrata for 5%
C glabrata infections are often resistant to azoles
Recurrent episodes require clinical examination, culture of swabs, and consideration of underlying disease
Male partners who do not have symptoms need not be examined, have swabs taken for culture, or be treated
Reduction of intestinal colonisation is of no value in preventing recurrence
Working Group of the British Society for Medical Mycology
Vaginal candidiasis (candidosis) is one of the most common infections seen in general practice. Up to three quarters of all women will suffer at least one episode of this condition during their lifetime, around half of them suffering a further episode.1 Most women who develop symptomatic candidiasis suffer from infrequent isolated episodes and respond well to local or oral antifungal treatment. In some, however, the infection is recurrent, while others have persistent symptoms that fail to respond to treatment.
Candida albicans is the most important cause of both superficial and deep forms of candidiasis. Its rate of isolation in swabs taken from women with vaginal infection is between 80% and 95%.2 3 The second most common fungus recovered from the genital tract of women with vaginitis is Torulopsis glabrata, now reclassified as C glabrata, which accounts for about 5% of vaginal infections. Infections with C glabrata are apt to be milder, but they should not be ignored if the patient has symptoms as the organism is often resistant to antifungal treatment.
The extent to which C albicans can be regarded as a normal inhabitant of the genital tract is unclear. On the one hand, Carroll et al found that clinical signs of infection could be detected in all pregnant women from whom the fungus was isolated, even those without symptoms.4 On the other hand, numerous reports describe C albicans in vaginal swabs taken from women without symptoms or clinical signs of vulval or vaginal infection.3 5 6 7 8 These observations suggest that changes in the host vaginal environment are required before the fungus can exert its pathological effects. The changes that allow symptomatic vaginal infection with C albicans to occur are unknown, but the condition has been associated with several precipitating factors.
Vaginal candidiasis is much more common in pregnant women. Moreover, a large proportion of women with chronic recurrent candidiasis first present with the infection during pregnancy. Vaginal colonisation and infection are also more common among women with diabetes mellitus. Broad spectrum antibiotic treatment may also predispose to vaginal candidiasis. Oral contraception and aberrations in iron metabolism, however, are no longer regarded as significant precipitating factors.
In contrast to women who have infrequent episodes of vaginal candidiasis, women with chronic or recurrent infection seldom have recognisable precipitating or causal factors.9 These women tend not to use oral contraception or to have been frequently prescribed broad spectrum antibiotics; they also tend to have normal results in glucose tolerance tests.
Most women with vaginal candidiasis complain of intense vulval and vaginal pruritus with or without vaginal discharge. The condition often develops quickly, and in women who are not pregnant it tends to begin during the week before menstruation. Some women complain of recurrent or increasing symptoms preceding each menstrual period. Dysuria and dyspareunia are common.
Vulval erythema with fissuring is the most common clinical finding (fig 1). This is often localised to the mucocutaneous margins of the vaginal introitus and the fourchette, but it can spread to affect the labia majora and the perineum. Vaginitis with discharge is often commonly found (fig 2). Thick white adherent plaques on the vulval, vaginal, or cervical epithelium are the classic signs of florid vaginal candidiasis in pregnant women. Often the discharge is thick and white, but it can be thin or even purulent.
Vaginal candidiasis is but one of several causes of vaginal discharge and must be distinguished from other conditions (box). These include trichomoniasis, bacterial vaginosis, and chlamydial and gonococcal infections. Other causes of mucosal pruritus include herpes infection and allergies (including reactions to topical antifungal treatment). Other causes of pruritus are contact dermatitis and psoriasis.
More than one pathogen can cause a genital tract infection. Simultaneous infection with C albicans and Trichomonas vaginalis is, however, unusual.2 3 5 C albicans is also less common among women with non-specific genital infection, among contacts of men with non-specific urethritis, and among women with bacterial vaginosis.3
Women with recurrent vaginal candidiasis often develop psychosexual problems as a result of their illness. These should be considered as part of the differential diagnosis.
Differential diagnosis of vaginal candidiasis
Contact dermatitis or allergies
Acute pruritus vulvae
In general practice symptoms such as pruritus and vaginal discharge are commonly the basis for diagnosing candidiasis, sometimes without even a genital examination. Patients' assessment of symptoms of discharge is not, however, a reliable method of diagnosing candidiasis.10 Among the different symptoms and clinical signs associated with this condition only pruritus and objectively assessed discharge are reliable clinical indicators of infection.11
Swabs need not be taken for fungal culture on a first visit if typical signs and symptoms are present, unless a sexually transmitted disease is possible (in which case all appropriate swabs should be taken). If symptoms persist despite antifungal treatment, however, patients should be examined and specimens obtained for mycological and other microbiological investigations.
The most reasonable approach to the diagnosis of vaginal candidiasis is to consider both symptoms and clinical signs with the results of culture of vaginal specimens or of microscopical examination of smears of vaginal secretions (fig 3), or both. Isolation of the causal organism is a more sensitive method of diagnosis than is finding it in vaginal smears.12 13 The isolation of a scanty growth of C albicans from patients without symptoms should not be regarded as a basis for treatment. Patients should be treated, however, if they have symptoms and only a few colonies of yeast are isolated. Several investigations in which semiquantitative culture methods were used have shown that the greater the amount of yeast recovered the greater the likelihood that patients will have symptoms and clinical signs typical of vaginal candidiasis.11 14 Swabs are not an ideal means of obtaining quantitative microbiological results, but moderate or heavy growth is usually indicative of clinical disease.
Specimens for mycological investigation should be obtained after insertion of a vaginal speculum. This also allows endocervical swabs to be taken to test for chlamydial and gonococcal infections. Swabs should be taken from discharge in the vagina and from the lateral vaginal wall and placed in transport medium. The effect of different transport media on the survival of C albicans has not, to our knowledge, been investigated, but the yeast can survive on swabs stored at room temperature for up to 24 hours before being plated out.15 Storage temperature can adversely affect the survival of other vaginal pathogens.
Swabs from patients with suspected candidiasis should be inoculated on to plates of glucose peptone or malt agar containing chloramphenicol and then incubated at 37°C for 48 hours. Isolates should be tested for germ tube production as this is a rapid (takes 1-2 hours), cheap (costs less than 50 pence), and specific test for C albicans. Most isolates of Candida spp that do not produce germ tubes can be identified with one of the numerous commercial methods that are now available. Identification is particularly important if patients fail to respond to antifungal treatment as some organisms, such as C glabrata, may be insensitive to fluconazole.
In general practice Gram stained slide preparations of vaginal discharge need not be specifically examined. If, however, smears are being examined for other pathogens, such as T vaginalis, oval, budding cells and hyphal forms are indicative of C albicans infection.
Commercial latex agglutination tests to detect C albicans antigens in vaginal secretions are useful for the rapid diagnosis of vaginal candidiasis.8 16 17
Most women with vaginal candidiasis respond to topical treatment with nystatin or an imidazole, such as clotrimazole or miconazole. A few women have recurrent infection and require special management, which we will discuss later.
Five imidazole derivatives—clotrimazole, econazole, isoconazole, ketoconazole, and miconazole—are available in several topical formulations for the treatment of genital candidiasis. Clotrimazole, econazole, ketoconazole, and miconazole nitrate are marketed as creams for vulvitis, and clotrimazole, econazole nitrate, isoconazole nitrate, and miconazole nitrate are marketed as pessaries. These drugs, most of which are produced in different formulations, give higher cure rates than nystatin with shorter courses of treatment, and all of them have a similar, low relapse rate. Treatment times range from one to six nights. Shorter regimens achieve better patient compliance,18 but treatment courses of less than six nights should be reserved for first episodes. If further tests are performed to confirm cure, vaginal specimens should not be taken until at least three to four days after the end of treatment.
Itraconazole and fluconazole have been licensed for the short term oral treatment of vaginal candidiasis. Fluconazole is given as a single dose of 150 mg and itraconazole as two doses of 200 mg eight hours apart with food. These drugs are more expensive than topical preparations, but patient compliance is improved.19 Futhermore, if the vulva is very inflamed an oral preparation is much less painful to administer.
Nystatin was the first polyene antifungal to be applied to the treatment of vaginal candidiasis. It is still one of the cheapest agents for the treatment of this condition, but it requires a longer treatment period (two weeks) and has a lower cure rate than the topical or oral azoles.20 It is not available without a prescription, but it is often useful in women whose condition has failed to respond to azole treatment.21
The many preparations and recommended treatment regimens attest to the need for further improvements in the treatment of vaginal candidiasis. Recommended regimens are not clearly related to differences between drugs, possibly owing more to commercial considerations than to careful comparisons.
Management of recurrent candidiasis
Recurrent vaginal candidiasis is a difficult problem to manage. Patients often suffer from depression. They may already have or will develop psychosexual problems as a result of their illness. Correct diagnosis is vital, and patients should be encouraged to avoid potential precipitating factors, though these may not be obvious. Other diagnoses include herpes simplex infection, allergic reactions, and bacterial vaginosis. Physical examination, investigations to exclude diabetes mellitus (and possibly HIV infection), and mycological investigation are essential and, if possible, should be performed when the patient has symptoms but has had no treatment.
There is no need to investigate oral or intestinal colonisation with C albicans in women with recurrent vaginal candidiasis. In the past, clinicians often attributed recurrent infection to repeated reinoculation of the genital tract from a persistent intestinal reservoir. This belief was based on the finding that patients often harbour the same strain of C albicans in the genital and intestinal tracts.22 23 24 Two controlled trials showed, however, that oral nystatin treatment, given to reduce intestinal colonisation with C albicans, failed to prevent recurrence of symptoms of vaginal infection.25 26
Asymptomatic colonisation of the male genital tract by C albicans is about four times more common in partners of infected women.27 Moreover, strain typing methods have indicated that infected partners often harbour identical strains.22 24 28 The role of sexual transmission in vaginal infection is unknown, and topical or oral treatment of the male partner does not seem to prevent recurrence in the woman. In most cases, recurrence of symptoms probably results from vaginal relapse after inadequate treatment of a previous episode.9 The endometrium is not a common reservoir for yeasts, and therefore infection there is an unlikely cause of recurrent vaginal candidiasis.29 Whatever the source of vaginal reinfection or relapse, women with recurrent candidiasis differ from women with infrequent episodes in being unable to tolerate small numbers of organisms reintroduced or persisting in the genital tract. Strain typing methods have shown that women with recurrent and infrequent infection usually harbour the same strains of C albicans.23
Most patients with recurrent candidiasis can be managed with intermittent prophylactic treatment with a single dose or multiple doses of topical or oral antifungals given to prevent symptomatic episodes. Local treatment with clotrimazole or miconazole at every two to four weeks suppresses symptoms even if mycological cure is not achieved.30 31 Intermittent single doses of oral fluconazole 150 mg are also effective.9 After symptoms have been suppressed for three to six months, regular treatment can be discontinued and the patient reassessed. Many women do not revert to the previous pattern of frequent recurrence.
Although antifungal drug resistance does sometimes have a role in treatment failure, other factors such as allergic reactions or poor compliance are much more common reasons for a poor clinical or mycological response. Nevertheless, drug resistance should be considered if yeasts other than C albicans are recovered from swabs taken from women with recurrent vaginal candidiasis. By comparison with C albicans, isolates of C glabrata are much less sensitive to fluconazole and other azoles.21 Women with recurrent C glabrata infection can sometimes be managed with nystatin or boric acid treatment. Such patients are best referred to a specialist.
Patients with recurrent candidiasis often resort to home remedies, such as vaginal yoghurt douches or special diets, and there is no doubt that some women derive some benefit from them. Other general measures recommended for the prevention of candidiasis include wearing loose fitting cotton underwear and avoiding the wearing of tights altogether. Little data are available on the efficacy of these measures. Likewise, discontinuation of the oral contraceptive pill has little scientific support.
In men genital candidiasis usually presents as a balanitis or balanoposthitis. Patients often complain of soreness or irritation of the glans penis; less commonly they have subpreputial discharge. Maculopapular lesions with diffuse erythema of the glans penis are often present; occasionally, there is oedema and fissuring of the prepuce. Itching, scalign, cutaneous lesions are sometimes found on the penis or in the groin. Men with insulin dependent diabetes may present with an acute fulminating oedematous form of balanoposthitis with ulceration of the penis and fissuring of the prepuce. White plaques can be found on retraction of the prepuce. About a fifth of male contacts of women with recurrent vaginal candidiasis complain of soreness and itching of the glans penis soon after intercourse and lasting for 24-48 hours. Men who have a penile catheter inserted long term or those using Paul's tubing are prone to chronic or recurrent penile candidiasis.
Diagnosis should not be on clinical grounds alone as balanitis and balanoposthitis have other causes. Specimens for mycological investigation should be taken from the coronal sulcus and subpreputial sac. Patients should be investigated for diabetes mellitus.
Genital candidiasis in men should be treated with saline washes or local applications of an antifungal cream. Nystatin should be applied morning and evening for at least two weeks. Clotrimazole, miconazole, or econazole creams should be applied for at least one week. Female partners should also be investigated. Men who fail to respond to treatment should be referred to a specialist for investigation for other infectious or non-infectious causes of their condition. Long term antifungal treatment may be appropriate for those with recurrent penile candidiasis associated with catheters or drainage devices.
The members of the working group are Dr D W Denning (chairman), Department of Infectious Diseases and Tropical Medicine, University of Manchester; Professor E G V Evans, Public Health Laboratory Service Mycology Reference Laboratory, Department of Microbiology, University of Leeds; Dr C C Kibbler, Department of Medical Microbiology, Royal Free Hospital, London; Dr M D Richardson, Regional Mycology Reference Laboratory, Department of Dermatology, University of Glasgow; Dr M M Roberts, University Department of Dermatology, Hope Hospital, Salford; Dr T R Rogers, Department of Infectious Diseases and Bacteriology, Royal Postgraduate Medical School, London; Dr D W Warnock (rapporteur), Public Health Laboratory Service Mycology Reference Laboratory, Public Health Laboratory, Bristol; Dr R E Warren, Public Health Laboratory, Royal Shrewsbury Hospital, Shrewsbury.
We thank Dr B Goorney and Dr J Roberts, consultant genitourinary physicians, for comments on the manuscript; we also thank Dr Goorney for providing the figures.