Practical strategies for acute and recurrent vaginitis
Self-diagnosis and treatment are out, and meticulous, in-office diagnosis is in—and there is new hope for women with chronic candidiasis: maintenance fluconazole.
IN THIS ARTICLE
“Last hope” to end recurrent infections
Sandra, 46, makes an appointment to discuss her recurrent vaginal infections. In the past year, she has had numerous episodes of itching, burning, and abnormal discharge and has used “everything” to treat them. She has tried an array of antifungal and antibiotic preparations, but has experienced only transient relief. She says you are her last hope to break the cycle of recurrent infections.
How do you respond?
Although vaginitis is usually considered a minor nuisance, many women experience chronic symptoms that persist or recur after treatment. For patients such as Sandra, chronic vaginitis is a constant source of frustration and a serious threat to quality of life.
Careful diagnosis is the first and most important step to eradicate vaginitis, and this article describes the essential components—as well as common pitfalls. In some cases, high-dose therapy or maintenance regimens may be indicated; these strategies are also described in detail.
The usual suspects
Vaginitis is defined as inflammation of the vagina marked by pain, itching, and/or a purulent discharge. Depending on the population, the most common causes of infectious vaginitis are:
- bacterial vaginosis (BV) (22%–50% of symptomatic women),
- vulvovaginal candidiasis (VVC) (17%–39%), and
- trichomoniasis (4%–35%).1
However, vaginitis in 7% to 72% of women remains undiagnosed.1 Their symptoms may be caused by atrophic vaginitis, vulvar dermatological conditions, vulvodynia, or other entities.
The hazards of self-diagnosis
Although a wide range of pathogens can cause vaginitis and symptoms are often nonspecific, the trend in the past decade has been for women to diagnose and treat themselves for VVC. The reasons: availability of over-the-counter (OTC) antifungals, ability to rapidly initiate antimycotic therapy, empowerment of women, and the likelihood of reducing direct and indirect healthcare costs.2
Unfortunately, recent studies suggest that self-diagnosis may not be as beneficial as we thought. Ferris and colleagues3 studied 601 women in a variety of medical and community sites in Georgia and found that only 11% without and 34.5% with a prior diagnosis of VVC could accurately recognize it or bacterial vaginosis.
A later prospective study4 of 95 symptomatic women purchasing OTC antifungal agents found that only 34% had pure VVC; treatment with a topical antifungal would have been inappropriate or inadequate in the rest, many of whom had bacterial vaginosis.
A more recent longitudinal study5 of women who submitted yeast cultures every 4 months for a year found no correlation between antecedent Candida colonization and subsequent antifungal use.
Avoid telephone diagnosis, too. Although telephone conversations are useful for patient triage and treatment in many clinical situations, diagnosis of vaginal symptoms by telephone correlates poorly with the actual diagnosis.6
If it’s really VVC, it should respond to antifungals. Over-the-counter antifungals are as effective as their prescription counterparts, so women with VVC should respond to OTC therapy. If a woman reports a lack of response, question the initial diagnosis and offer a thorough evaluation instead of recommending further treatment as the initial step.
Even the pros can be wrong
In a review of 52 medical records of women referred to a tertiary-care vaginitis center, Wiesenfeld and Macio7 found that vaginal pH testing was performed at only 3% of office visits and that 42% of referring physicians failed to perform microscopy as part of their evaluation.
In a study of 61 women diagnosed with VVC after clinical examination and microscopy in a university-based outpatient gynecology clinic, Ledger et al8 found that 49% had a negative yeast culture and polymerase chain reaction.
Office-based tests, even when they are performed in the best of circumstances by personnel focused on vaginal symptoms, have relatively low sensitivity: 92% for bacterial vaginosis, 62% for Trichomonas, and a mere 22% for yeast. 9
The right test matters
Given the nonspecific nature of vulvovaginal symptoms and the limitations of office-based testing, a few tests are nevertheless useful for patients with chronic symptoms or an unclear diagnosis.
Yeast cultures. When VVC is suspected, cultures increase sensitivity and allow for speciation of the organism. Speciation is crucial to choosing the proper antifungal drug.
Trichomonas cultures. Because a wet mount has low sensitivity in diagnosing trichomoniasis, Trichomonas cultures are useful in selected patients (with >90% sensitivity), such as women with a previous diagnosis of trichomoniasis, those at risk for sexually transmitted disease (STD), or those with microscopy showing BV or leukorrhea.
When Trichomonas cultures are unavailable, the OSOM Trichomonas Rapid Test (Genzyme Diagnostics, Cambridge, Mass) has better sensitivity than microscopy to detect Trichomonas vaginalis.
Herpes cultures and antibodies. Because genital herpes often presents with mild or nonspecific symptoms, a herpes simplex virus (HSV) culture and type-specific immunoglobulin-G HSV antibodies should be ordered when the patient presents with fissures or ulcers of the vulva.
Forget the gram stain. Given the relatively high sensitivity (92%) of Amsel criteria to diagnose bacterial vaginosis and the difficulty of obtaining Nugent scores on gram stains of vaginal secretions, the value of gram stains outside of research settings for women with suspected bacterial vaginosis is unclear.
Vulvar biopsies. Many women who complain of vaginitis actually have vulvar disorders.
Be prepared to obtain vulvar biopsies if necessary.
INTEGRATING EVIDENCE AND EXPERIENCE
High-dose treatment (and maybe condoms) improved cure rate
Although metronidazole gel 0.75% is a standard BV therapy in the United States, much higher doses in combination with nystatin are common in other countries such as Peru. They proved more effective in a recent randomized trial, suggesting that high doses or more prolonged courses of therapy may be beneficial when standard treatment fails.
In the single-blind trial, Sanchez and colleagues24 compared 5 nights of metronidazole gel 0.75% (37.5 mg per dose) to the same duration of treatment with intravaginal ovules containing 500 mg metronidazole and 100,000 U nystatin.
Patients were asked to return 14, 42, and 104 days after treatment; 138 (91%) of 151 women returned at least once.
At every follow-up, the women treated with the ovules had significantly lower recurrence rates (4%, 17%, and 33% for the ovules, compared with 20%, 38%, and 52% for the gel).
Was use of condoms related? Although participants were not randomized for condom use, recurrent infection was more likely among women whose partners did not use them.
The trial’s strengths and limitations
This study is notable for its long follow-up, blinding of the evaluator and biostatistician, and diagnostic methods (both Amsel and Nugent criteria).
The trial addressed the question of whether early recurrence is due to persistent pathogenic flora or failure to repopulate the vagina with hydrogen-peroxide–producing lactobacilli.The improved cure rate with the higher dose of intravaginal metronidazole ovules suggests that it more effectively eradicated abnormal flora than the lower dose.
However, the condom finding suggests that exposure to some factor associated with the partner also plays an important role.
The main limitation was the variability of elapsed time for follow-up visits. For example, the range for the first visit was 10 to 132 days; as a result, some women had a first evaluation that was much later than others.
Further, because participants were Peruvian, the applicability to a US population with potentially different demographics or sex practices is unclear.
Watch for complicated VVC
Women who harbor Candida organisms in their vaginas have VVC. At one end of the spectrum are women who are asymptomatically colonized. It is not necessary to treat these women or make an effort to identify the organisms. At the other end of the spectrum are symptomatic women, who have been traditionally treated with a variety of antifungal therapies, now available in multiple formulations.
Many experts now believe VVC should be classified as complicated or uncomplicated (TABLE 1) to help identify women in whom therapy is likely to fail. Uncomplicated VVC has cure rates of 80% to 90%.10 In contrast, several studies suggest that women with complicated VVC have lower short-term cure rates with either topical clotrimazole or oral fluconazole. 10,11
Most women with recurrent VVC fall into the complicated category. For the most part, these are normal, healthy women who experience substantial discomfort and disruption of their daily well-being and sexuality because of recurrent infections. Self-treatment permits rapid initiation of antimycotic therapy, but does nothing to prevent the next symptomatic episode.
Criteria for candidiasis diagnosis
UNCOMPLICATED (meets all criteria)
Cure rate of 80% to 90%
Sporadic or infrequent episodes
Mild to moderate symptoms or findings
Suspected Candida albicans infection
Normal, nonpregnant woman
COMPLICATED (meets 1 or more criteria)
Cure rates vary widely
Recurrent (4 or more episodes per year)
Severe symptoms or findings
Suspected or proven non-albicans Candida infection
Adapted from Sobel JD, et al.26
Which Candida sp is it?
When standard antimycotic therapy fails, the species of infecting organism seems to be particularly important. Women with Candida glabrata colonization have markedly lower cure rates than women colonized with C albicans.11 Thus, a crucial first step in treating women who have complicated VVC is obtaining a yeast culture. A positive culture helps corroborate the diagnosis, increases the sensitivity of the evaluation, and allows speciation of the organism and proper selection of therapy.
Non-albicans species less likely to respond to standard azole therapy. Candida glabrata is the second leading cause of VVC, but is less responsive to standard therapies. For example, cure rates of perhaps 50% can be expected with a 7-day course of terconazole cream.12
When azole therapy is ineffective, intravaginal boric acid in 600-mg capsules can be used every night for at least 14 days and will be effective in about two thirds of patients. 13 However, some patients have accidently ingested these boric acid capsules and died (apparently this dose of boric acid is lethal when taken orally). Thus, it is crucial that patients be warned specifically about this hazard.
In a series of 30 patients with no response to azole therapy and subsequent boric acid, Sobel and colleagues achieved a cure rate of 90% with a 14-day course of flucytosine cream 17%, given in 5-g nightly doses.13
Watch for false negatives in women on azole therapy. In general, the C albicans organism tends to be sensitive to azole therapy. Thus, if a woman with C albicans infection is cultured while on therapy, the odds are very high that she will have a negative yeast culture.
Maintenance therapy with ketoconazole for recurrent VVC was first proposed in 1986, but was never widely adopted due to concerns about liver toxicity.
More recently, maintenance fluconazole was found to be effective in a doubleblind, placebo-controlled study.14 After treating the initial infection with 3 doses of fluconazole (150 mg every 3 days), researchers randomized women to a 6-month course of weekly fluconazole (150 mg) or placebo. During the 6-month treatment phase, relapse was noted in 9% of the fluconazole group and 64% of the placebo group. However, of the 126 fluconazole-treated women who were disease-free at the end of the treatment phase, 72 (57%) experienced relapse during the next 6 months.
Fluconazole for 6 months. Although about 50% of women have a relapse after stopping treatment, most can at least successfully control and prevent symptomatic episodes as long as they are using fluconazole in maintenance doses. Most experts recommend a 6-month course of maintenance therapy.