Bioadhesive product
In women with complicated infections either due to non-albicans species or chronic/recurrent vulvovaginal candidiasis, more aggressive therapy may be indicated. In women with recurrent or severe disease, there is benefit to repeat doses. In a randomized placebo-controlled trial of 387 women with severe or recurrent vulvovaginal candidiasis, two sequential doses of 150 mg given three days apart compared to a single 150 mg dose showed a significantly higher cure rate, 67% improved to 80%.[34] In women with frequent, recurrent vulvovaginal candidiasis (greater than four episodes per year), initial intensive therapy followed by maintenance dosing has been shown to decrease symptomatic relapse. This therapy was described by Sobel to include an initial intensive therapy with three 150 mg doses of fluconazole at 72-hour intervals followed by once weekly dosing of 150 mg fluconazole orally or placebo for six months. This therapy decreased recurrence rates significantly and showed prolonged remission in approximately 50% of women.[35]
Refractory infections may be due to non-albicans species or less likely azole-resistant Candida albicans. Non-albicans species are often resistant to many of the azoles. Vaginal boric acid (600 mg) prescribed in a gelatin capsule for 14 days or amphotericin B suppositories are effective for refractory cases from Candida glabrata.[36] In patients in whom boric acid fails, a success of 90% was achieved with a two-week course of topical 17% flucytosine (5 g intravaginal dose).[37] This therapy can be used in combination with amphotericin B. None of these therapies should be used in pregnancy.
At this time, there is no evidence that probiotics or partner treatment is effective to prevent recurrences. Patients with multiple episodes of vaginal candidiasis may benefit from evaluation for conditions associated with immunocompromised conditions such as diabetes or human immunovirus (HIV) infection.
Bacterial vaginosis
Bacterial vaginosis (BV) is a change in a woman’s natural vaginal flora in which the normal vaginal lactobacilli are replaced by a variety of anaerobic bacteria and mycoplasmas. The major bacteria that have been identified include Gardnerella vaginalis, anaerobic gram-negative rods belonging to the genera Prevotella, Porphyromonas, and Bacteroides, as well as Peptostreptococcus species, Mycoplasma hominis, Ureaplasma urealyticum, and often Mobiluncus species.[38] BV is the most common cause of vaginal discharge in women of childbearing age. In the United States, the National Health and Nutrition Examination Survey estimated the prevalence of BV to be 29% in the general population of women aged 14–49.[39]
There are several risk factors for BV including sexual activity and IUD use.[39] Condoms are associated with a decreased risk of BV, as is the use of combined hormonal contraception pills.[40] The association of IUD use and BV appears to be mediated by irregular bleeding and those without irregular bleeding did have an increased risk for BV.[41] Other risk factors include douching and cigarette smoking.[42]
The classic symptoms of BV include thin, gray, homogenous discharge that is malodorous. Other symptoms may include a yellowish discharge, abdominal pain, intermenstrual bleeding, and menorrhagia. Physical exam findings include the presence of abnormal discharge, malodorous smell, and rarely evidence of inflammation.
The gold standard for the diagnosis of BV is a Gram’s stain. It is used mostly in research studies. BV is more commonly diagnosed clinically based on Amsel’s criteria. Amsel’s criteria requires the presence of three out of four defined criteria: abnormal gray discharge, vaginal pH greater than 4.5, a positive amine or “whiff” test, and more than 20% of the epithelial cells being clue cells on a wet mount.[43] Amsel’s criteria have a sensitivity of 92% and specificity of 77%.[44]
There are several commercially available tests to aid in the diagnosis of BV when microscopy is not available. The BD Affirm VPIII test is an automated DNA probe assay for detecting Gardeneralla vaginalis when present at a high concentration (2 × 105 CFU/mL). It is able to detect three infectious agents – G. vaginalis, Candida species, and Trichomonas vaginalis – making it useful in the detection of mixed infections.[45] Another available test is the OSOM BVBlue system. This system is a chromogenic diagnostic test based on the presence of elevated sialidase enzyme activity in vaginal fluid samples. This enzyme is produced by bacterial pathogens associated with BV including Gardenerella, Bacteroides, Prevotella, and Mobiluncus species.[46, 47] There is no role in the diagnosis of BV for vaginal cultures.
In nonpregnant women, BV is associated with an increased risk of chlamydia, gonorrhea, herpes simplex virus type 2, and trichomoniasis.[48–50] BV has also shown to increase transmission rates of HIV.[51] It has been implicated in the development of pelvic inflammatory disease and post-procedural gynecologic infections.[52] In pregnant women, several studies have shown a relationship of BV infection to early miscarriage, late miscarriage, preterm labor, low birth weight, prematurity, preterm premature rupture of membranes, histologic chorioamnionitis, and postpartum endometritis.[53–55]
Currently recommended therapies for the treatment of BV are listed in Table 22-2. The listed regimens have comparable safety and efficacy and therefore treatment should be individualized.[56, 57] Topical therapy is more expensive than oral systemic therapy, although the later is associated with more gastrointestinal side effects. Short-term treatment response rates approach 84%.[56, 58] BV, however, persists or recurs in 11%–29% of women at one month and 30% of women relapse within three months. Recurrence rates may be as high as 50% within one year.[59] Standard therapy is effective for the treatment of BV in pregnant women, so those with symptomatic BV should be treated.[60]
Probiotic therapy has not yet shown a clear benefit to reduce recurrences. Studies of partner treatment have also failed to show any significant benefit.[61]
Trichomoniasis
Trichomoniasis is a common nonviral STD worldwide. The total prevalence in the female population was estimated at 3%, affecting non-Hispanic black women most frequently with a prevalence of 13.3%. Prevalence in this population increases with age. Trichomoniasis is found 18%–50% in women with vaginal complaints.[62]
Trichomoniasis is caused by a single cell, flagellated protozoan Trichomonas vaginalis. Coinfection with BV is common with rates as high as 60%–80%.[63] Risk factors include multiple sexual partners, low socioeconomic status, history of other sexually transmitted diseases, and lack of condom use.
Symptoms of trichomonal infections include frothy, gray or yellow-green vaginal discharge. It is often associated with pruritius, burning, dysuria, abdominal pain, post-coital bleeding, or dyspareunia. Up to 50% of women are asymptomatic.[64] Physical exam may reveal erythema or inflammation of the vulva and vagina, cervical petechiae, or strawberry cervix.[65, 66]
The diagnosis of trichomoniasis relies on the visualization of motile trichomonads on wet mount. A wet mount has only 55%–60% sensitivity in the diagnosis of trichomoniasis and depends on the experience of the technician and collection technique.[67] Other findings on wet mount that may suggest the presence of trichomonads include an elevated pH and increase in PMNs.
The gold standard for diagnosis is polymerase chain reaction (PCR). PCR is available from Gen-Probe as the APTIMA Trichomoniasis assay. This assay uses target capture and transcription mediated nucleic acid amplification testing (NAAT) to detect species specific ribosomal RNA, including N. gonorrhea, C. trachomatis, and T. vaginalis. This technology is highly sensitive (100%) and specific (99%) and can be performed on urine and self-collected samples.[68] Other commercially available tests include rapid antigen or nucleic acid probes including the BD AFFIRM VPIII and the OSOM Trichomonas Rapid Test.
Trichomoniasis has been implicated in numerous studies to increase the risk of transmission of HIV [69–71] and increase the risk of CIN.[72] It has also been shown to increase the risk of atypical PID in HIV positive women.[73] Similarly to BV, it increases the risk of posthysterectomy cuff cellulitis and abscesses.[52] In pregnant women, it is associated with an increased risk of adverse pregnancy outcomes including PPROM and preterm labor.[74]
Treatment of trichomoniasis is further discussed in the chapter on sexually transmitted diseases.
Desquamative inflammatory vaginitis
Desquamative inflammatory vaginitis (DIV) is a rare but disabling condition.[5] The prevalence of DIV is unknown, although it has been reported to be as high as 8% of a referral population to a specialty vulvovaginitis clinic.[5] Reichman and Sobel characterized the largest cohort of women with DIV and described these women as mostly Caucasian, perimenopausal, more likely to have thyroid disease and allergic diatheses, and more likely to respond to anti-inflammatory therapy.[75]
The etiology of DIV remains unknown. Possible etiologies have included vitamin D deficiency, unidentified microbial pathogen, diminished estrogen, autoimmune disorder, cell-mediated immune activation, and possible genetic link.[76] Most likely DIV represents a heterogeneous group of disorders with common clinical and microscopic characteristics.
Women with DIV report profuse, purulent vaginal discharge; DIV is very frequently associated with vulvar soreness, burning, and dyspareunia.[77] Patients may also describe itching and irritation. Almost all women are symptomatic.[78] Physical exam findings can include significant erythema with marked inflammation and even erosive findings. The visible discharge is typically purulent and without odor.
DIV is diagnosed clinically. The classic findings on microscopy include an elevated number of PMNs, predominance of parabasal cells (immature squamous cells) and vaginal pH greater than 4.5. Clinical and microscopic findings mimic those found in other conditions like trichomoniasis and vaginal atrophy. DIV is, therefore, a diagnosis of exclusion and N. gonorrhea, C. trachomatis, and T. vaginalis must be excluded.
Treatment for DIV is mostly derived from case reports. There are no large, randomized studies. Regimens have included intravaginal steroids either alone or in combination with clindamycin vaginal cream. Studies have shown reasonable response rates. Treatments are summarized in Table 22-3. In a small study of 51 women treated with intravaginal 2% clindamycin, the overall improvement was 90% with symptomatic relapse occurring in 29%.[79] Women are treated for two to four weeks. Given the high risk of recurrence, multiple maintenance regimens have been proposed. Consideration of twice weekly intravaginal steroids has been used for prevention of recurrences.[78]
Other disorders
Other less common disorders may also cause symptoms of vulvar and vaginal irritation and increase in vaginal discharge. In postmenopausal women, patients commonly present with atrophic vaginitis. These women report abnormal vaginal discharge, dryness, itching, burning and/or dyspareunia. Diagnosis is made on the basis of elevated pH, parabasal cells on microscopy, and negative amine test. There are no clue cells present. It is possible to have elevated polymorpholated neutrophils (PMNs) on microscopy with advance disease. Treatment consists of topical estrogen therapy and/or water based vaginal moisturizers.[80, 81]
Foreign bodies such as retained tampons may also cause an increase in vaginal discharge. These are almost always characterized by significant vaginal discharge that is reported as malodorous. It is treated simply with removal of the foreign body. Vaginal dysplasia is found less frequently than vulvar and cervical dysplasia. It is typically HPV mediated. Lesions are highly variable; therefore, any suspicious findings on exam warrant biopsy. Other even more rare disorders include group A Streptococcus infections, which can cause profuse vaginal irritation and purulent discharge.
Concluding remarks
Vulvovaginal disorders are prevalent among women. A complete history and physical exam is important in the evaluation of the women with these symptoms. Basic clinical exam and laboratory testing will aid in the diagnosis of most of these disorders so that treatment can be tailored to the woman and her diagnosis, thereby improving clinical outcomes.