eMedicine Specialties > Obstetrics and Gynecology > General Gynecology
Vulvovaginitis
Updated: Apr 30, 2009
Introduction
Background
Vulvovaginitis is the most common gynecologic condition seen by practitioners rendering primary care to women. The term vulvovaginitis is a semantic compromise that categorizes many vaginal infections as vulvovaginitis because the 2 are interrelated. Discharge, burning, and pruritus are the most common symptoms, accompanied by signs of vulvar irritation such as erythema and excoriation of the vulvar skin.
Traditionally, the 3 classic entities of vaginitis include bacterial vaginosis, Trichomonas infection, and candidiasis. However, this article focuses on topics that are primarily inflammatory disorders and affect the vulvar region.
Pathophysiology
The vulva, the external genitalia of the female, includes the labia majora and minora, the clitoris, and the vestibule of the vagina. During the reproductive years of a healthy woman's life, the vagina maintains a moist environment that is in constant fluctuation. The secretion of an alkaline transudate from the vaginal epithelium and cervical glands maintains this moist environment with a pH ranging from 3.8-4.5. In addition, the vagina and its microflora form a unique balanced environment that can change under pressure from external stimuli but returns to normal with removal of the stimuli. It can vary in degree during the menstrual cycle, pregnancy, and sexual activity.
The vaginal epithelium consists of 3 cell layers: superficial, intermediate, and basal. These cells are capable of storing glycogen under the influence of estrogen. Glycogen is available in the fully mature cells in the superficial layer of the epithelium. With elevated levels of either exogenous or endogenous estrogen, all levels of the epithelium thicken as a result of glycogen storage. With diminishing levels of estrogen, the layers become thin and atrophic.
In an adult woman's reproductive years, the bacterial flora of the healthy vagina contains numerous microorganisms, including aerobic and anaerobic gram-positive and gram-negative bacteria. Lactobacillus and Corynebacterium predominate over other bacteria such as Streptococcus, Bacteroides, Staphylococcus, and Peptostreptococcus. Both Lactobacillus and Corynebacterium produce lactic and acetic acid from glycogen, thus maintaining the low vaginal pH. Additional bacteria are kept in check by the acid-producing bacteria and are rarely pathogenic, but they may become pathogenic if the environmental balance is affected.
The skin of the vulva is sensitive to the vaginal environment and hormonal, metabolic, and allergic influences. It is composed of stratified squamous epithelium that contains hair follicles, sebaceous sweat glands, and apocrine glands.
Differential Diagnosis
The focus of this article includes Candida vulvovaginitis, atrophic vaginitis, contact dermatitis, pediatric vulvovaginitis, and vulvar vestibulitis.
The complete differential includes the following:
- Allergic reaction
- Physiologic leukorrhea
- Atopic dermatitis
- Lichen simplex chronicus
- Lichen sclerosus
- Paget disease
- Psoriasis
- Vulvodynia
In prepubertal girls with vaginal discharge, the following should be considered:
- Anatomic abnormality
- Foreign bodies
- Neoplasm
- Sexual abuse
- Hygiene
Vulvovaginal Candidiasis
In the United States, estimates indicate that approximately 50% of college-aged women will have an episode of vulvovaginal candidiasis. At some point in their lifetime, nearly 75% of all women experience an attack of Candida vulvovaginitis. Approximately half of these women have more than 1 episode, and a few have frequent relapses.
Etiology
Vulvovaginal candidiasis can be an acute, chronic, recurrent, or persistent condition that can involve the vulva, vagina, and adjacent crural areas. The specific causative agent belongs to the genus Candida. These organisms are found in almost all humans and many animals. An estimated 10-50% of reproductive-aged American women are considered opportunistic carriers. Candida albicans is identified approximately 85-90% of the time. Recently, an increased frequency of other Candida species, such as Candida glabrata, Candida tropicalis, and Candida krusei, has been reported. The emergence of these other Candida species may possibly be due to widespread use of over-the-counter drugs, long-term use of suppressive azoles, and the use of frequent short courses of antifungal drugs.
Predisposing agents
Any host factor that affects the vaginal environment or vaginal secretions can play a role in the initiation of Candida vulvovaginitis. Pregnancy is one of the most common predisposing factors. Studies have demonstrated that up to one third of pregnant women worldwide on any day can be affected. The high levels of reproductive hormones and an increase in the glycogen content in the vaginal environment create a favorable environment for Candida species. In combination, these 2 changes provide an abundant source of carbon for candidal growth, germination, and adherence. Furthermore, the acidity of the pregnant vaginal flora can suppress the growth of other microorganisms that are naturally inhibitory to Candida. Although the initial attachment of the organism occurs more readily at high pH values (6-7), the germ tube formation and the development of mycelia are favored by a low vaginal pH (<5).
Older studies of women using high-dose estrogens in oral contraceptives found an increase in vaginal colonization by Candida. The mechanism is believed to be similar to that found in pregnancy. However, the newer oral contraceptives with a lower estrogen dose do not seem to predispose the patient to Candida vulvovaginitis.
Disorders associated with an altered immune response, such as acquired immunodeficiency syndrome (AIDS) and diabetes mellitus, also predispose to Candida vulvovaginitis.
Antimicrobials are thought to predispose a patient to Candida by reducing the number of protective resident vaginal bacteria. The most common offenders are broad-spectrum agents such as tetracycline, cephalosporins, and ampicillin-like agents.
A study by Horowitz et al in 1987 demonstrated Candida species in ejaculate fluid of partners of patients with recurrent Candida infections. They suggested that the carrier rate might be low.1 Traditionally, vulvovaginal candidiasis is not considered a sexually transmitted disease because it occurs in celibate women, and Candida itself is considered part of the normal vaginal flora.
Clinical
In acute vulvovaginal candidiasis, vulvar pruritus and burning are the main symptoms. Patients commonly complain of both symptoms after intercourse or upon urination. Dyspareunia may develop and become severe enough to lead to intolerance of intercourse. Physical findings include erythema and edema of the vestibule and labia majora and minora. The rash may extend to the thighs and to the perineum. Thrush patches are usually found loosely adherent to the vulva. A thick, white, curdlike vaginal discharge is usually present.
The clinical picture of chronic persistent candidiasis differs in that it includes marked edema and lichenification of the vulva with poorly defined margins. Often, a grayish sheen made up of epithelial cells and organism covers the area. Symptoms include severe pruritus, burning, irritation, and pain. This patient group is usually older, obese, and often has long-standing diabetes mellitus.
Diagnosis
The diagnosis depends both on the demonstration of a species of Candida and the presence of clinical symptoms. Diagnostic tests include a positive wet-mount test or potassium hydroxide preparation. Vaginal pH usually remains normal in vulvovaginal candidiasis.
The wet-mount test involves microscopic examination of vaginal discharge or scrapings from vulvar lesions mixed with physiological saline under both low-power and high-power magnifications. Under microscopic viewing, the spores and conidia are visible. The presence of yeast blastospores or pseudohyphae can be detected in approximately 30-50% of patients with symptomatic vulvovaginal candidiasis. Adding 10% potassium hydroxide to the solution lyses white blood cells, red blood cells, and vaginal epithelial cells, making the alkali-resistant branching budding hyphae of Candida easier to see. This method may increase the sensitivity; however, at least one third of patients with symptomatic candidiasis have negative findings with this method. Nevertheless, positive results from these 2 tests, in combination with a normal vaginal pH, are helpful in confirming the diagnosis.
Most studies demonstrate that 85-90% of vaginal isolates are C albicans. As a result, fungal cultures have not been used by most clinicians as part of the initial evaluation. The rationale is thought to be that using fungal cultures will be too sensitive and will detect yeast that may be colonizing the patient, but not causing the symptoms.
Treatment
The cell wall of the organism is a complex glycoprotein that depends on the biosynthesis of ergosterol. Azole compounds found in antimycotic drugs are believed to block this step in biosynthesis. Topical antimycotic drugs can achieve cure rates in excess of 80%. The only oral azole agent approved for this indication by the US Food and Drug Administration (FDA) is fluconazole, which also achieves a high rate of cure. It achieves therapeutic concentrations in vaginal secretions for at least 72 hours after the ingestion of a single 150-mg tablet.2
In considering treatment, distinguishing between sporadic or recurrent episodes of vulvovaginitis is of great importance. Uncomplicated sporadic vaginitis usually is caused by strains of C albicans. The majority of these strains exhibits sensitivity to azole-based antifungal agents and thus, usually are responsive to all forms of antifungal therapy. To date, no overall difference has been observed in studies regarding the in vitro activity and clinical efficacy of the various azole topical agents listed in the Table below for the treatment of uncomplicated cases. Thus, practitioners can begin with an empiric trial of treatment without relying on cultures. In uncomplicated cases, selection of treatment usually is based on patient preference.
A number of antimycotic regimens are available for the treatment of vulvovaginal candidiasis, including oral and topical agents. Consideration must be taken regarding drug interactions with oral usage. Hepatotoxicity secondary to ketoconazole therapy occurs in approximately 1 in every 10,000-15,000 individuals exposed to this drug. Adverse effects also can include nausea, abdominal pain, and headaches. Drug interactions may occur with simultaneous use of calcium channel antagonists, warfarin, cyclosporine, oral hypoglycemic agents, protease inhibitors, theophylline, and rifampin, to name a few.
Before 1980, the topical agents approved by the FDA for the treatment of acute vulvovaginal candidiasis included nystatin, miconazole, and clotrimazole. Since then, butoconazole and terconazole have been approved. In comparative trials of 10- to 14-day courses of therapy, the azoles have resulted in higher rates of clinical and mycological cure (80-95%) than nystatin (70-80%). In addition, the azoles have been more efficacious even when given for a shorter durations than the 14 days required for nystatin.
Table 1. Suggested Treatment Options as Cited in the US Centers for Disease Control and Prevention Guidelines for TreatmentOpen table in new window
Table
| Butoconazole | 2% cream, 5 g intravaginally for 3 days |
| Butoconazole | 2% cream, 5 g (Butaconazole1-sustained release), single intravaginal application |
| Clotrimazole | 1% cream, 5 g intravaginally for 7–14 days |
| Clotrimazole | 100 mg vaginal tablet for 7 days |
| Clotrimazole | 100 mg vaginal tablet, 2 tablets for 3 days |
| Miconazole | 2% cream 5 g intravaginally for 7 days |
| Miconazole | 100 mg vaginal suppository, one suppository for 7 days |
| Miconazole | 200 mg vaginal suppository, one suppository for 3 days |
| Miconazole | 1,200 mg vaginal suppository, one suppository for 1 day |
| Nystatin | 100,000-unit vaginal tablet, 1 tablet for 14 days |
| Tioconazole | 6.5% ointment 5 g intravaginally in a single application |
| Terconazole | 0.4% cream 5 g intravaginally for 7 days |
| Terconazole | 0.8% cream 5 g intravaginally for 3 days |
| Terconazole | 80 mg vaginal suppository, 1 suppository for 3 days |
| Fluconazole | 150 mg oral tablet, 1 tablet in single dose |
| Butoconazole | 2% cream, 5 g intravaginally for 3 days |
| Butoconazole | 2% cream, 5 g (Butaconazole1-sustained release), single intravaginal application |
| Clotrimazole | 1% cream, 5 g intravaginally for 7–14 days |
| Clotrimazole | 100 mg vaginal tablet for 7 days |
| Clotrimazole | 100 mg vaginal tablet, 2 tablets for 3 days |
| Miconazole | 2% cream 5 g intravaginally for 7 days |
| Miconazole | 100 mg vaginal suppository, one suppository for 7 days |
| Miconazole | 200 mg vaginal suppository, one suppository for 3 days |
| Miconazole | 1,200 mg vaginal suppository, one suppository for 1 day |
| Nystatin | 100,000-unit vaginal tablet, 1 tablet for 14 days |
| Tioconazole | 6.5% ointment 5 g intravaginally in a single application |
| Terconazole | 0.4% cream 5 g intravaginally for 7 days |
| Terconazole | 0.8% cream 5 g intravaginally for 3 days |
| Terconazole | 80 mg vaginal suppository, 1 suppository for 3 days |
| Fluconazole | 150 mg oral tablet, 1 tablet in single dose |
Most women with vulvovaginal candidiasis usually respond quickly to one of the therapies described above. Despite therapy, recurrent vulvovaginal candidiasis, defined as 4 or more episodes of infection per year, occur in less than 5% of healthy women. Predisposing factors for recurrent infection are apparent in only a minority of women, and include poorly controlled diabetes and immunosuppressive therapy. Other factors that may predispose to recurrent infection include abnormalities in local vaginal mucosal immunity and genetic susceptibility. Studies have found that women with recurrent infections have a higher frequency of certain Lewis blood group antigens and specific gene polymorphisms compared with controls.
Recurrent vulvovaginal candidiasis has been associated with a decreased in vivo concentration of mannose binding lectin (MBL) and an increased concentration of interleukin-4 (IL-4). Studies have shown that the prevalence of a variant MLB gene is higher in women with recurrent vulvovaginal candidiasis than in controls without candidiasis. Furthermore, IL-4 blocks the anti-Candida response mediated by macrophages; thus, elevation of IL-4 levels result in inhibition of local defense mechanisms.3,4,5,6
The role of sexual transmission in recurrent infection remains unresolved. Although controversial, most studies do not support treatment of sexual partners.7 Horowitz et al reported on 54 women with recurrent candida vaginitis. One half of the male partners were treated with ketoconazole, 200 mg/d for 5 days. No significant difference was found in the rate of relapse between women with untreated or treated partners.1
Recurrences may be caused by other species of Candida that are not equally susceptible to the usual first-line treatments. In vitro studies have shown that imidazole antifungal agents, such as miconazole and clotrimazole, are not as effective against non– C albicans fungi. C tropicalis and C glabrata are 10 times less sensitive to miconazole than is C albicans. Appropriate fungal cultures may be taken to identify the species. Treatment entails longer courses of antimycotic therapy (10-14 d) regardless of the route of administration.
Several studies have shown the effectiveness of antifungal maintenance suppressive therapy for several months. Although an optimal regimen has not yet been established, regimens include ketoconazole (400 mg/d), itraconazole (50-100 mg/d), fluconazole (100 mg/wk) for 6 weeks, and clotrimazole (500-mg vaginal suppositories once per wk). These regimens have been used for up to 6 months.
Topical boric acid8 has been used for decades as a treatment for vulvovaginal candidiasis. Although it often is effective, it is classified as a poison and may be absorbed systematically through the vaginal mucosa. For protection, it is encapsulated in a gelatinous capsule and administered as a suppository. Treatment includes 600 mg in size 0 gelatin capsule intravaginally daily for 2 weeks.
In addition to medical treatment, studies have shown that ingested sucrose and lactose may support and promote the growth of yeast. Having patients limit their dietary intake of such sugars may help. Patients are advised to wear loose-fitting nonocclusive clothing and cotton underwear to avoid providing the warm moist climate in which Candida tends to thrive. Some providers recommend washing clothing in hot water and using panty liners to avoid creating a reservoir for the fungus.
Atrophic Vaginitis
Etiology
Extremely low estrogen production, as found after menopause or bilateral oophorectomy, can lead to atrophy of the vaginal and vulvar epithelium. Vulvovaginal atrophy is considered a natural process after estrogen withdrawal. Although menopause is the leading cause of decreased levels of circulating estrogen, atrophy of the vagina can occur in nonmenopausal women. In nonmenopausal women, ovarian estrogen production can be diminished by cancer treatments, such as radiation therapy and chemotherapy, and immunologic disorders. Furthermore, in postpartum women, the decline in estrogen levels in conjunction with the loss of placental estrogen and the antagonistic action of prolactin on estrogen production during lactation can lead to atrophy.
Among its many effects, estrogen helps to maintain the collagen content of epithelium and thus affects its thickness and elasticity. It also helps to maintain acid mucopolysaccharides and hyaluronic acid, which keep epithelial surfaces moist. During the reproductive years, estrogen stimulation is responsible for maintenance of a well-epithelialized vaginal vault. It causes the nonkeratinized stratified squamous epithelium of the vagina to be thick, rugated, and rich in glycogen. Glycogen is necessary for rapid multiplication and maintenance of lactobacilli.
During the perimenopausal period, estrogen secretion, primarily estradiol, remains at approximately 120 ng/L. After menopause, it decreases to approximately 18 ng/L. The reduction of endogenous estrogen causes thinning of the epithelium and a diminished glycogen content. The lack of glycogen contributes to a reduction in lactic acid production and an increase in vaginal pH, thus leading to the overgrowth of nonacidophilic species and the disappearance of Lactobacillus. In some patients, this new flora may include the introduction of bacteria that can incite a superficial infection in denuded regions and alter vaginal secretions.9
In addition, during estrogen withdrawal, the papillae of the vagina flatten and the rugae nearly disappear, leaving the vagina relatively smooth. The mucosa becomes progressively thinner and eventually may become only a few cell layers thick. A moderately thick layer of intermediate cells may be present in some areas, with only a row of basal cells in others. Eventually, the vagina becomes denuded of epithelium.
Clinical
Most women with mild-to-moderate vaginal atrophy (60-90%) are asymptomatic or have symptoms that cause no distress to them. Clinical symptoms include vaginal soreness, postcoital burning, dyspareunia, burning leukorrhea, and occasional spotting. Pronounced symptoms of atrophic vaginitis generally appear only after estrogen levels have been low for an extended period of time.
Early on, women may notice a slight decrease in vaginal lubrication upon arousal, which is one of the first signs of estrogen insufficiency. As the hypoestrogenic state becomes chronic, additional symptoms arise. The most common symptom is vaginal spotting, which usually results from a break in the thin vaginal mucosa. Dyspareunia may result from ulceration of the vulvovaginal epithelium. The vagina is noted to be thin, with occasional petechia and diffuse redness with few or no vaginal folds. A serosanguineous discharge may be present, with a pH of 5-7. A wet mount often shows white blood cells and a paucity of Lactobacillus.
Treatment
Accumulating evidence indicates that the vaginal symptoms readily respond to estrogen treatment. With treatment, mucosal thickening with glandular function can be maintained well into the postmenopausal period. Estrogenic effect on vaginal cytology is quantified by using the maturation index by using vaginal smears from the lateral walls of the upper one third of the vagina.10
Treatment usually entails the use of topical vaginal estrogen for 1-2 weeks to alleviate symptoms. An increase in superficial cells and vaginal maturation index occurs at levels of plasma estrogen that are barely above those of menopause. Once symptoms improve, continuation of treatment at decreased intervals is necessary for maintenance. An oral estrogen regimen can also be used.
Studies demonstrate that vaginal creams produce serum estradiol levels one-fourth that of oral estrogen but are 4-times more potent than oral estrogen on the vagina. Treatment can be continued indefinitely, although safety data for treatment beyond 1 year have not been established.
The choice of modality for local estrogen administration should be guided by patient preference, taking into account factors such as cost and convenience. A systematic review of 16 randomized trials investigating local estrogen treatment of vaginal atrophy found that creams, pessaries, and rings were all similarly effective in relieving the symptoms.11
Numerous studies have used different treatment regimens; treatment usually is selected based on clinician preference. The manufacturers of Premarin vaginal conjugated estrogen cream suggest 0.5-2 g applied 3-7 times per week for 3 weeks, followed by 1 week without, for 3-6 months.
The advantages of vaginal estrogen cream include lower plasma levels and that it is more efficacious than oral treatment. However, disadvantages include compliance issues due to the application process itself and its messiness. For this reason, the silastic vaginal ring (Estring) and vaginal tablets (Vagifem) were developed.
The vaginal ring (Estring) is placed into the vagina to release controlled small doses of estrogen daily (7.5 mcg of estradiol).12 . Serum estrogen is slightly increased but usually remains in the menopausal range. The ring has noted to be at least of equal efficacy to vaginal estrogen cream in regards to tissue integrity and patient acceptance. It is intended to be used continuously for 90 days and can be used during sexual intercourse.13
Vagifem is a vaginal tablet that contains 25 g of 17-beta estradiol and has been demonstrated to be well tolerated and effective. In a 12-week, double-blind, randomized, placebo-controlled study by Eriksen et al, Vagifem was found to improve symptoms compared with placebo. Again, treatment is clinician-based, with a common regimen being 1 tablet daily followed by a twice-weekly maintenance application.14
In regards to the risk of unopposed estrogen and risk of endometrial proliferation and possible subsequent endometrial carcinoma, studies, although short-term, have not demonstrated a risk. Estradiol levels in the range of less than 70 pmol/L have been shown to be associated with atrophy of the endometrium. These forms of estrogen all maintain plasma levels well below 30 pmol/L during steady state. In a study of 60 postmenopausal women randomly assigned to receive Estring or no treatment for 12 months, no significant increases in endometrial thickness were observed in either group. Similar results have been reported with estrogen vaginal tablets. Thus, the risk of endometrial carcinoma is considered minimal. However, any amount of estrogen absorption may be clinically relevant in a patient with breast cancer.11
Hormone therapy is not the only option for postmenopausal women. Women who cannot or do not want to take hormones may decide to take nonpharmacological therapies, such as herbal treatments. Herbal treatments are used widely by women; however, they remain largely unstudied by the scientific community. A survey by the North American Menopause Society indicated that up to 10% of women use herbal therapies for menopausal symptoms.15
Three agents that have been under study include dong quai, black cohosh, and isoflavones.
Many women in both Europe and the United States have used dong quai, a traditional Chinese herb extracted from the Angelica sinensis root, for menopausal symptoms. In a small study of 71 women with hot flashes, patients were given either dong quai daily (4.5 g) or placebo for 6 months. The study did not find a difference in endometrial thickness or in the vaginal maturation index between the 2 groups. Although women in both Europe and the United States use this herb alone, Chinese practitioners prescribe it in conjunction other herbs. Dermatitis secondary to photosensitization is a common adverse effect of this drug.16
Black cohosh (Cimicifuga racemosa) is marketed as a precursor of progesterone that has estrogenlike effects. It is a phytoestrogen that contains triterpene, a flavonoid, and has been used in Germany for decades to treat menopausal symptoms. It has been found to reduce levels of luteinizing hormone, but not follicle-stimulating hormone, in menopausal women. According to a few studies, extract doses of either 2 tablets or 40 drops twice daily can safely reduce menopausal symptoms. Data are limited, and no data are available on toxicity. In rare cases, it can cause stomach upset. It has an additive hypotensive effect when combined with antihypertensives. The recommended dosage is for a maximum duration of 6 months.17
Phytoestrogens are naturally occurring plant sterols that have both estrogenic and antiestrogenic effects in humans. They include isoflavones (found in soybeans), coumestans (found in red clover and alfalfa sprouts), and lignans (found in oil seeds such as flaxseed).
Phytoestrogens are absorbed and converted by the intestinal flora into compounds that resemble estrogen. They then bind with and activate human estrogen receptors. If endogenous estrogen levels are high, they exhibit antiestrogenic effects; however, in postmenopausal women in whom levels are diminished, they are found to exhibit estrogenic properties.18
Interest in isoflavones escalated after observation that Asian women, who consume much more isoflavones than Western women, experience fewer menopausal symptoms. A small study of menopausal Thai women demonstrated that only 27% reported menopausal vasomotor symptoms as opposed to 85% of Western women.19
Studies, although limited, have demonstrated small increases in vaginal superficial cells with the ingestion of isoflavone. However, no significant increase in follicle-stimulating hormone or luteinizing hormone has been demonstrated.
Other nonhormonal therapies include vaginal moisturizers and lubricants. The lubricant is used just before intercourse, and the moisturizer is used long-term to relieve symptoms. Nachtigall et al examined the effect of a moisturizer, Replens, compared with conjugated estrogen cream (Premarin) in a randomized 12-week trial with 30 patients. Replens was administered 3 times weekly with an applicator, and the cream was used at 1.25 mg/d. The results demonstrated that both produced lower pH levels; however, the estrogen produced a statistically significantly greater effect on vaginal elasticity within 4 weeks. The Replens increased elasticity over a longer period of time. It also reversed vaginal atrophy in 60% of patients compared with 100% of patients receiving estrogen.10
Vulvar Vestibulitis
Etiology
The vestibule consists of nonpigmented and nonkeratinized squamous epithelium devoid of skin. It contains mucus-secreting minor vestibular glands, ductal orifices of the Bartholin glands, Skene glands, and the urethral meatus. It is within this region that the inflammatory entity vulvar vestibulitis arises.
Vulvar vestibulitis is a condition that was first recognized more than a century ago. Skene described it in 1889 as a condition of "excessive sensitivity" and "hyperesthesia." Although recognized years ago, this condition remains poorly understood.
While many theories have been proposed, the etiology of this condition remains unknown. Vulvar vestibulitis was not widely recognized until Woodruff and Parmley reported it in the 1980s.20 They thought that the etiology was an infection of the vestibular glands that was best treated by perineoplasty. In 1988, Pyka et al studied surgically excised specimens of the vulvar vestibule of 41 patients with vulvar vestibulitis. Pyka identified it in 66% of the specimens' minor vestibular glands. All of these glands demonstrated some degree of squamous metaplasia forming the vestibular clefts.21
Freidrich coined the name vulvar vestibulitis in 1987.22 Other names noted in the literature include focal vulvitis, minor vestibulitis gland syndrome, periglandular vestibulitis, vestibulodynia, and erythematous vulvitis en plaques. Despite several different names, the classic definition according to Freidrich's criteria includes the following signs and symptoms confined to the vulvar vestibule: (1) severe pain upon touching the vestibule or attempted vaginal entry, (2) tenderness to pressure localized within the vulvar vestibule, and (3) physical findings confined to vestibular erythema of various degrees.
Several theories have attempted to discover an etiology for this entity. Histopathological studies have not been helpful in that they have demonstrated a nonspecific inflammation of the vestibular region affecting mostly the superficial stroma and occasionally the epithelium. Marinoff and Pyka proposed that Candida may be a causative organism; however, the presence of yeast in these patients with vulvar vestibulitis has not been confirmed by other reports. Some authors believe that it may be secondary to the use of several types of topical medication that may have produced an allergic sensitization within the vulvar vestibule while being used for the treatment of vulvovaginal candidiasis.
More recent studies have investigated the role of human papilloma virus (HPV) infection; however, the evidence has been controversial.23 Turner and Marinoff24 reported a 100% rate of HPV positivity in vulvar biopsies in 7 patients with vestibulitis, while Bergeron reported negative viral findings in all 11 of his biopsies. Further studies are needed to elucidate the relationship, if any, between HPV and vulvar vestibulitis.
Several other agents have been implicated in the etiology of vulvar vestibulitis. Therapeutic agents used in the treatment of clinical and subclinical HPV25 , such as cryosurgery, trichloroacetic acid, podophyllin, and laser treatment, also have been implicated. Several cases have been reported after the use of 5-fluorouracil cream. Chemical irritants, such as those found in feminine hygiene products, also have been investigated as possible initiating agents.
Alkaline vaginal pH has been demonstrated to cause irritation to the vestibule. Any etiological cause that alters the vaginal pH can lead to overgrowth of anaerobic and/or disappearance of the normal flora, ie, Lactobacillus. Hypotheses suggest that the constant bathing of the vestibule by an alkaline vaginal discharge may lead to chronic irritation and inflammation. Finally, some authors have associated vulvar vestibulitis with a history of sexual abuse, elective abortions, severe marital conflicts, depression, and anxiety.
Recent studies have begun to focus on specific pain receptors found in the vulvar tissue. As a brief overview, the sensory innervation of the inferior portion of the vulva is primarily from the branches of the pudendal nerve. The ilioinguinal and branches of the genitofemoral nerve innervate the superior portion of the vulva. These nerve fibers are of 2 types: (1) those responsible for touch and (2) others responsible for nociception (perception of a noxious stimuli). The mechanism hypothesized is that the nociception fibers are innervated first instead of the touch fibers. This is followed by a prolonged innervational response of the nociception fibers, leading to an abnormal neurological response from the dorsal horn of the medulla.
Westrom and Willen tested this theory by obtaining vulvar biopsies of 47 women with clinical vestibulitis. In 44 specimens, they noted that not only were regions of marked increase of vestibular nerve formation present, but a significant correlation was found between inflammation and nerve-bundle density. The authors concluded that a chronic inflammatory reaction in the vestibule might lead to proliferation of nerve fibers. Thus, treatment had entailed surgical removal of these nerve fibers.26
Clinical
Women who are first affected are usually young, sexually active, and of Caucasian origin. Most patients have endured their symptoms for several months and have empirically tried various remedies with no improvement. Vulvar vestibulitis, or vestibulodynia, can be divided into primary and secondary forms. Primary vestibulodynia (20% of cases) is introital dyspareunia that starts from initiation of sexual activity or intolerable pain consistently present upon insertion of a tampon or vaginal speculum in women who have never been sexually active. Secondary vestibulodynia is introital dyspareunia that develops after a period of comfortable sexual relations, tampon use, or speculum examinations.
Usual symptoms include pain, soreness, burning, and a feeling of rawness that is aggravated by stress, exercise, tight clothing, coitus, and tampon use. The pain is usually not considered constant; it is elicited by any attempt to enter the vagina. Many patients complain of an irritating vaginal discharge and a vulvar burning sensation. Examination may reveal small spots of erythema around the vestibular glands, with rare ulceration. Lesions are predominantly found in the lower portion of the vestibule. Unfortunately, standard pelvic examination typically reveals no physical findings. Gentle pressure with a cotton-tipped applicator around the base of the hymenal ring and posterior fourchette usually elicits the pain.
Treatment
Considerable controversy exists regarding the optimum mode of treatment. Many therapeutic regimens have been used with varying success. Of the treatments listed, most have not been evaluated prospectively and are based on clinical experiences reported in the literature.
Generally, no specific cure is available, but spontaneous resolution has been reported; thus, treatment should focus on alleviation of symptoms. Pain management has consisted of modalities such as sex therapy, behavioral modifications27 , biofeedback27 , and acupuncture.
Remedies that have been used with some success include topical application of anesthetics such as 5% Xylocaine ointment applied 15-30 minutes prior to intercourse. Other treatments include the use of a protective coating, such as from petroleum jelly or A&D ointment, to minimize contact with any irritating vaginal discharges; topical corticosteroids; wet compresses with aluminum acetate; and anti-inflammatory agents.
A case report by Solomons in 1991 demonstrated the use of oral calcium citrate combined with a low oxalate diet. He noted that calcium oxalate crystals released in urine might act as an irritant in the development of vulvar vestibulitis. He recommends a low oxalate diet with the ingestion of calcium citrate (200 mg calcium and 950 mg citrate) to theoretically inhibit the formation of calcium oxalate crystals.28 Many authors recommend this trial of treatment; however, studies are lacking with regard to benefit.
A number of trials have used alpha interferon and noted to have some success. The idea was initiated after noting the success of this agent with condylomata acuminata. Horowitz et al treated 17 women with severe vulvar vestibulitis with intravestibular injections of alpha interferon, one million units 3 times per week for a period of 1 month. His findings noted that 15 of the 17 women demonstrated considerable improvement. Favorable response was gauged by improvement of clinical symptoms such as dyspareunia.29 However, recommendations at this time indicate that alpha interferon should be used as a mode of treatment for women who present with concomitant HPV infections.
Since the etiology of pain is neuropathic, recent research has focused on pharmacological treatment that addresses neuropathic pain. Medications such as gabapentin and pregabalin have been used with success. In one study of 152 women with vulvar pain treated with gabapentin, 98 (64%) achieved resolution of at least 80% of their symptoms.30
As a last resort, surgical excision may be considered. Woodruff and Parmley developed the
original surgical mode of treatment. They described a U-shaped excision of the posterior hymenal ring 0.5 cm on each side of the hymen starting 0.5 cm below the urethra on each side. In their study, they reported that women who fulfilled the criteria of vulvar vestibulitis who underwent surgery demonstrated a success rate of 80%.20 Most studies have reported success rates of 60%. Postoperative complications are uncommon but include dehiscence, hematoma, infection, uneven healing, or nodular excrescences along the suture line.
In the 1980s, excision by carbon dioxide laser microsurgery of the Bartholin gland or glands, followed by excision of the vestibular tissue, was used in an attempt to relieve pain thought to be caused by HPV. Healing was noted to be prolonged, and complications such as scarring and further pain led to the general abandonment of this technique.
Contact Dermatitis
Etiology
The vulvar skin is a frequent site of contact dermatitis. The cutaneous response may be allergic or irritant-induced. An allergic reaction implies previous exposure to an allergen and sensitization. It is a cell-mediated (type IV) immunologic response that can occur in sensitized individuals. Irritant-induced contact dermatitis can be acute or chronic. It may occur from acute exposure to a potent irritant or upon repeated exposure to a weak irritant.
Predisposing agents
Irritants include moisture, urine, vaginal discharge, topical medications, anticandidal agents, latex, spermicide agents, cosmetics, douching, fragrances, cleansing products, and underwear.
Clinical
Clinical symptoms consist of varying degrees of tenderness, pain, burning, and pruritus. Urinary retention may occur in severe cases.
Pruritus is the cardinal symptom. However, an acute reaction may develop as a result of exposure to a potent irritant that involves the mucosa, leading to burning, rawness, and pain. This initially presents as red and edematous skin followed by exudation and weeping, which may lead to secondary infections. The irritant also may be potent enough to cause erosion, ulceration, or necrosis.
Repetitive exposure to weak irritants with an insufficient period of healing and restoration of skin integrity between each exposure characterizes chronic contact dermatitis. Contact dermatitis of long duration may include lichenification, scaling, thickening of the skin, and white plaques.
When the mechanism is an allergen, the symptoms may not be apparent until 24-48 hours after contact, as opposed to immediate symptoms with an irritant.
Diagnosis usually is based on the patient's history and physical examination.
Treatment
Literature is limited on treatment options. Most treatment regimens are empiric and based on clinical experience.
The first step towards treatment is removal of the inciting agent. Patch testing may be necessary for allergen identification. Avoidance of sexual intercourse, douching, detergents, soaps, and perfumes is essential. Mild vulvovaginal reactions usually subside rapidly after the causative agent is withdrawn.
Cleansing can be accomplished by gentle flushing of the area once a day with clear water and patting the area dry. Triamcinolone ointment, 0.1% applied twice a day, can help in irritant contact dermatitis. Severe lesions can be treated with wet compresses of aluminum acetate solution for 30 minutes several times a day. After each application, the vulvar skin must be kept clean and dry.
Hydrocortisone (0.5-1%) and fluorinated corticosteroids as lotions or creams may be helpful to reduce symptoms and usually are most beneficial with true allergic reactions. Additional treatment can include antihistamines and sodium bicarbonate sitz baths.
Conclusion
The differential diagnosis for women with symptoms of vulvovaginitis is complex. Discharge, burning, and pruritus usually are the presenting symptoms, with signs of vulvar irritation that may include erythema and excoriation of the vulvar skin. Primary or secondary infections, skin irritants, or contact dermatitis may produce vulvar irritation. Irritation from bodily fluids such as urine and normal vaginal secretions may cause symptoms when the environment is kept moist as with tight-fitting or occlusive clothing.
Because each disorder produces a similar clinical presentation, a careful history must be taken, an examination must be performed, and the vaginal discharge should be examined. Along with medical treatment, the patient must be encouraged to avoid etiological agents and to make necessary changes in her habits.
Keywords
Candida vulvovaginitis, vulvovaginal candidiasis, vaginal infection, atrophic vaginitis, contact dermatitis, pediatric vulvovaginitis, vestibulodynia, vulvar vestibulitis, focal vulvitis, minor vestibulitis gland syndrome, periglandular vestibulitis, erythematous vulvitis en plaques, bacterial vaginosis, Trichomonas, candidiasis, Candida albicans, Candida glabrata, Candida tropicalis, Candida krusei, tetracycline, cephalosporins, ampicillinlike agents, group A streptococci, Streptococcus pyogenes, Haemophilus influenzae, Staphylococcus aureus
The authors and editors of eMedicine gratefully acknowledge the contributions of previous author Deslyn M Mancini, MD and Ellen Wood, DO, FACOOG to the development and writing of this article.
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Further Reading
Keywords
Candida vulvovaginitis, vulvovaginal candidiasis, vaginal infection, atrophic vaginitis, contact dermatitis, pediatric vulvovaginitis, vestibulodynia, vulvar vestibulitis, focal vulvitis, minor vestibulitis gland syndrome, periglandular vestibulitis, erythematous vulvitis en plaques, bacterial vaginosis, Trichomonas, candidiasis, Candida albicans, Candida glabrata, Candida tropicalis, Candida krusei, tetracycline, cephalosporins, ampicillinlike agents, group A streptococci, Streptococcus pyogenes, Haemophilus influenzae, Staphylococcus aureus
