Vaginal itching, discharge, and odor are among the most common complaints in gynecologic and primary care offices.1 Women often call their practitioners after self-treating at home. Self-diagnosis has been shown to be correct less than one-third of the time, leading to millions of dollars wasted on treating the wrong entity.2 Diagnosis by phone has also been shown to be only marginally better than chance. The symptoms of an infectious vaginitis are often confused and/or complicated by irritation, allergy, or other systemic diseases. Contact dermatitis and atrophy are similar in prevalence to candidiasis among patients referred for chronic vaginitis.3
Recognition and tailoring treatment to the correct disease process is paramount when managing patients with recurrent vulvovaginal symptoms. This involves seeing a patient, making a correct diagnosis, and treating any other conditions that may affect the success of the treatment chosen.
The natural defense of the vagina relies on protective organisms, intact epithelial cells, and often estrogen. Lactobacillus is the cornerstone of this protection, lowering the vaginal pH to create an environment unsuited to the growth of bacteria.4 It also inhibits bacterial adherence to epithelial cells and competes with them for nutrients. The vaginal equilibrium is affected by semen, arousal, tampons, menstrual blood, douching, antibiotics, and other contact irritants (Table 1).
Damage to the epithelial cells in the vagina due to trauma, bacterial overgrowth, or loss of estrogen can lead to difficulty in eliminating unwanted bacteria and increased sensitivity to the many irritants that come in contact with vulvovaginal tissue.5 Contact dermatitis can compound an otherwise “simple” infection and predispose women to recurrence due to a breakdown of their natural defenses.
Many cases of acute vaginitis can be easily treated when correctly diagnosed, however, some women will have persistent or recurrent disease. This article focuses on the more common causes of recurrent infectious vaginitis: Candidiasis and bacterial vaginosis (BV) and the methods used for their treatment and prevention.
BV is one of the most common causes of vaginal discharge. Its prevalence among college students is 5% to 25% and up to 61% in women with other sexually transmitted infections (STIs). It presents as profuse discharge with a fishy odor. Women who douche, are African American,6 smoke, or have more frequent intercourse or new partners are at higher risk of infection.7 Patients often consider the odor to be an indication of uncleanliness and so can exacerbate the situation with douching or other hygiene techniques that can allow the pathogen to further gain ground.
Vulvar irritation often accompanies these symptoms and can be a result of epithelial cell damage, irritation from the discharge, or irritating products that further damage the sensitive vulvar skin. Untreated BV not only causes irritating vulvovaginal symptoms, but has also been linked to other health consequences such as increased risk of preterm delivery, postpartum fever, post-hysterectomy vaginal cuff cellulitis, postabortal infection, endometritis, and an increased risk of acquiring a STI (HIV, herpes simplex virus, gonorrhea, chlamydia, and trichomonas).8 Effective treatment is essential to promote a woman’s overall health.
BV is the result of overgrowth of anaerobic organisms (eg, Gardnerella vaginalis, Prevotella, Mycoplasma, and Mobiluncus) in the vagina. The overgrowth of these organisms replaces lactobacilli and increases the vaginal pH.9 Lactobacilli can produce H2O2, which is a potent natural microbicide. The fishy odor is caused by the release of amines from vaginal peptides after breakdown by these organisms. Epithelial cell sloughing and vaginal transudate create the other symptoms experienced by women. The clinical diagnosis of BV is done by Amsel’s criteria, requiring 3 of the 4 criteria listed in Table 2. A Gram stain is the gold standard for the diagnosis of BV but its use clinically is limited by time and resources. Commercial tests are not widely used but can be if microscopy is not available. This can be expensive and time-consuming, so Amsel’s criteria is the preferred method of diagnosis. Amsel’s criteria has a sensitivity of over 90% as compared to Gram stain and is the most cost-effective method of diagnosis.
Culture has no role in the diagnosis of BV because G. vaginalis is detected over half of the time in healthy, asymptomatic women. BV should not be empirically treated if found on a Pap smear unless the patient is symptomatic.10
The mainstay of treatment for BV is metronidazole, orally or topically. Table 3 lists initial treatment regimens. Clindamycin regimens may be less effective than metronidazole but alternative regimens are offered for convenience, intolerance, or other issues that may preclude prescribing metronidazole. Tinidazole is also an option for those unable to tolerate the gastrointestinal side effects of metronidazole.11
Oral regimens are associated with more side effects than vaginal therapy with similar efficacy.12 These regimens offer high rates of cure, 70.5% to 80% at 1 month. However, more than 30% of patients will present with recurrence of symptoms at 3 months, and more than 50% will have recurrence by 12 months.
Performing a test of cure at the end of a treatment for a recurrent infection is one way to determine if subsequent infections are due to persistence of the initial infection or a reinfection. Cure is defined as all Amsel’s criteria-negative.9
Theories abound as to why recurrence rates are so high. One theory is that a normal vaginal ecosystem was not fully reestablished after initial therapy. Other possibilities include undertreatment of the initial infection, underlying predispositions, or behavioral risk factors. Reinfection is also another possibility. Whatever the cause, other therapies are often necessary to keep a woman free of symptoms. Retreatment with the initial regimen is a reasonable first step, keeping in mind that the longer therapy regimens may have more therapeutic success.10
Suppressive therapy has been shown to keep women in an asymptomatic state. This is typically done with monthly metronidazole. It is important to also counsel patients regarding lifestyle changes. Eliminating contact irritants such as douching and other irritating products will allow the vaginal ecosystem time to heal. The use of suppressive therapies seems to work while the medications are being used, but may not affect the rate of recurrence once stopped. Acidification of the vagina has not been shown to reduce recurrence rates and in fact, may worsen symptoms of irritation.9
The addition of probiotics is currently being evaluated as a way to keep the vaginal flora balanced and is a promising method of preventing the recurrence of BV. Using exogenous human bacteria to restore a normal flora seems to be a reasonable way to decrease BV, especially when used in conjunction with standard therapy.13 Probiotics have not been shown to definitively help decrease recurrence rates, but many studies show promise. The optimal route of administration, oral or vaginal, the appropriate strain, and correct dosing are all areas that would benefit from further study.12
Another treatment option involves the addition of boric acid to an oral nitroimidazole.14 Early studies have been promising, but more rigorous studies are needed.
While treatment of the partners of affected women has not been shown to help, sexual intercourse does appear to have a role in the disease process. It is not that BV is clearly a STI, but sexual risk factors certainly contribute to its transmission.15 There is evidence to support the use of condoms to decrease risk of recurrence. Risk of concordant infection is high in women who have sex with women and partners should be counseled about symptoms and seeking treatment when they occur.8
Currently, there is an unacceptably high rate of recurrence for BV. Some behavioral changes can decrease this risk, but other therapies are necessary to improve both the quality of life of those affected and decrease future health risk associated with the disease.
Vulvovaginal candidiasis is a common infection, affecting the majority of women at least once during their reproductive years, and more than 50% of women experience at least 2 infections.17 Up to 8% of women will experience recurrent vulvovaginal candidiasis, defined as 4 or more episodes per year. Many women self-treat and misdiagnose, making exact prevalences difficult to ascertain.
The primary symptom is vulvar pruritus but burning, soreness, and irritation also are common. Women will often present with edema, fissures, and excoriations from scratching. They may complain of burning with urination or dyspareunia. The classic discharge is thick, white, and clumpy.18 The primary culprit is Candida albicans, found in up to 90% of all cases. Any of the more than 100 species of C. albicans can cause the same symptoms. Candida glabrata is the most prevalent non-albicans species encountered and is not amenable to treatment with common vaginal and oral therapies used for Candida.19
The diagnosis of yeast is done with a microscopic evaluation of vaginal secretions. Hyphae or spores are often visible in normal saline or 10% KOH. A culture should be sent if the diagnosis is in question or if there are persistent or recurrent symptoms. This will confirm the presence of yeast and identify the strain for better clinical treatment. The vaginal pH may be lower than 4.5 but this is not always consistent.20
Yeast should be high on the differential in women with certain risk factors. Recent antibiotic use, diabetes, increased estrogen, immunosuppression, and coitarche have all been linked to an increase in infection.21
Many women are asymptomatic carriers of yeast; therefore, treatment should be focused on those experiencing symptoms. It is important to confirm the presence of yeast before initiating treatment as many women with vulvar pruritus will have a diagnosis other than yeast. The self-diagnosis of yeast should be discouraged, especially with recurrent infections and infections not linked to a known trigger because women tend to be wrong a significant amount of the time.18
A variety of oral and topical preparations are available for treatment of uncomplicated yeast infections (Table 4). These are appropriate if the infections are infrequent, symptoms are mild-moderate, the infection is likely C. albicans, and the patient is not pregnant. An uncomplicated yeast infection can be treated with either oral or topical therapy. Studies show comparable cure rates for oral and topical agents with equal relief of symptoms and a negative post-treatment culture in 80% to 90% of patients.18
Patients seem to prefer oral dosing for convenience, however, time to relief of symptoms may be slightly longer. Topical treatments tend to have fewer side effects. These factors support using patient preference and cost to guide treatment decisions.
Many of the medications used are over-the-counter and these can be effective methods of treatment, especially in uncomplicated infections. Guidelines from the Centers for Disease Control and Prevention are a good resource on first-line therapies for vulvovaginal candidiasis.
Complicated yeast infections are defined as recurrent infections, oc currence in immunocompromised patient, severe symptoms, occurrence in pregnant patients, or non-albicans species. These patients may be appropriate candidates for extended dosing of topical therapies or repeated oral doses. When a patient has more than 4 episodes of vulvovaginal candidiasis in a year, a more thorough examination of risk factors should be done.22
Women should be advised to eliminate all contact irritants, douching, and products that have allergens. Vulvar skin care guidelines should be implemented. A test of cure should be done after the treatment to ensure eradication. If the culture is positive after initial treatment, prolonged therapy is indicated in the symptomatic patient. A culture has been recommended in the case of recurrence to isolate the yeast strain for appropriate therapies. Non-albicans strains like C. glabrata may require the use of gentian violet or boric acid to treat.23 When a patient has had recurrence or is at high risk of recurrence, maintenance therapy may be reasonable. Weekly fluconazole has been shown to be effective in preventing recurrence but care should be taken with extended use due to possible liver complications. Maintenance therapy has been shown to reduce the risk of recurrence at both 6 months and 1 year.24 Vaginal therapies have few risks other than burning and irritation.25
Oral therapy, especially ketoconazole and itraoconazole, may have other drug interactions and may affect liver function. Fluconazole appears to have a better safety profile and its use does not automatically require laboratory monitoring. Data are lacking on use of probiotics. More studies are needed to demonstrate improvement and to direct dosing and route of administration.19
The question of treating sexual partners is somewhat controversial. If reinfection seems to be linked directly to sexual exposure, evaluation of the partner may be warranted and if no overt infection exists, a culture of oral or ejaculate specimens can be done.19 Recurrent yeast infections also tend to recur once suppressive therapy has been stopped. The rate may be as high as 30% to 40%. When that occurs, treatment may need to be episodic to prevent recurrences.
Because there is concern about fluconazole-resistant Candida, new therapeutic options are needed.17 Several non-conventional options for recurrent vulvovaginal candidiasis exist including lactobacillus and tea tree oil, which have potential but study of them may be difficult due to dosing and administration constraints.26
Both BV and vulvovaginal candidiasis are infections that are seen daily by most ob/gyns. It is important to recognize that many of the presenting symptoms overlap with one another and with other disease entities. Not all that itches is yeast. Clinicians must ensure that the diagnosis is correct through appropriate testing and examinations. Addressing other systemic comorbidities and giving appropriate counseling regarding contact irritants is time-consuming but necessary for proper therapy.
Prompt evaluation and treatment can help resolve symptoms and ensure a correct diagnosis. Both infections, however, can pose a challenge to clinicians with their propensity to recur. Patient education about risk factors and identification of an appropriate treatment regimen are crucial to curing these problems.
More data are needed on non-medicinal therapies aimed at prevention to minimize exposure to medications and improve the quality of life of affected women.
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