AUTHOR INFORMATION

Section 1 of 11

Authored by Anuritha Tirumani, MD, Research Coordinator, Department of Emergency Medicine, Brooklyn Hospital Center

Coauthored by Mark J Leber, MD, MPH, Clinical Assistant Professor of Emergency Medicine, Weill Medical College of Cornell University; Consulting Staff, Department of Emergency Medicine, Brooklyn Hospital Medical Center; Reza Keshavarz, MD, MPH, Clinical Assistant Professor, Departments of Pediatrics and Emergency Medicine, Mount Sinai School of Medicine; Director of Pediatric Emergency Medicine, Mount Sinai Hospital

Edited by David S Howes, MD, Residency Program Director, Professor of Medicine, Section of Emergency Medicine, University of Chicago/Pritzker School of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Mark Zwanger, MD, MBA, Assistant Professor, Department of Emergency Medicine, Thomas Jefferson University; John Halamka, MD, Chief Information Officer, CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine, Beth Israel Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School; and Pamela Dyne, MD, Program Director, Associate Professor, Department of Medicine, Division of Emergency Medicine, University of California at Los Angeles School of Medicine

Author's Email:	Anuritha Tirumani, MD
Editor's Email:	David S Howes, MD

eMedicine Journal, October 17 2006, VOLUME 7, Number 10

INTRODUCTION

Section 2 of 11

Background: Vulvovaginitis is common, affecting women of all ages. Vulvovaginitis is an inflammation of the vagina and vulva, most often caused by a bacterial, fungal, or parasitic infection. Vulvovaginitis, one of the most common reasons why women visit their gynecologist, causes vaginal discharge, irritation, and itching. Normally, a woman may have a vaginal discharge, the amount and consistency of which varies during the course of the menstrual cycle; however, vulvovaginitis causes a symptomatic increased vaginal discharge.

Etiologies and the approach of management for a patient with vulvovaginitis are age dependent. Vulvovaginitis can be divided into 3 age categories: premenarchal, childbearing, and postmenopausal.

Pathophysiology: The normal vaginal epithelium cornifies (develops into a thickened layer of epithelial cells) under the influence of estrogen, protecting women against infection. A normal vaginal discharge consists of 1-4 mL of fluid that is white or transparent, thick, and odorless. This physiologic discharge is formed by sloughing epithelial cells, normal bacteria, and vaginal transudate. The discharge may be noticeable during pregnancy, oral contraceptive pill use, or at mid menstrual cycle, close to the time of ovulation.

The normal pH of vaginal secretions is 4.0-4.5. The pH is maintained by lactobacillus, which produce hydrogen peroxide; diphtheroids, and Staphylococcus epidermidis. Vaginal pH may increase with age, phase of menstrual cycle, sexual activity, contraception choice, pregnancy, presence of necrotic tissue or foreign bodies, and use of hygienic products or antibiotics.

Bacterial vaginosis is secondary to bacterial overgrowth and not due to tissue inflammation. One of the organisms associated with bacterial vaginosis is Gardnerella vaginalis. Summarizing, practically any condition changing the vaginal milieu may result in vulvovaginitis.

Frequency:

• In the US:
  
  Premenarchal: Vulvovaginitis is the most common gynecologic problem affecting prepubertal girls and is responsible for the largest number of visits to the gynecologist.

  Childbearing age: Bacterial vaginosis is the most important cause of vulvovaginitis. Estimating the number of patients presenting with bacterial vaginosis is difficult because G vaginalis can be recovered from the vagina in 30-50% of asymptomatic women.

  Trichomonas vaginalis affects 2-3 million women annually in the United States. The organism also is detected in 30-40% of men who are exposed to women with T vaginalis. The prevalence of T vaginalis infection at clinics treating sexually transmitted diseases (STDs) varies from 8-31%. In men, T vaginalis may account for as many as 17% of cases of nongonococcal, nonchlamydial urethritis. T vaginalis infection appears to be more common in the southern United States.

  Candidal vulvovaginitis is considered slightly less common than bacterial vaginosis, yet, 3 out of every 4 women in the United States will have at least 1 bout of vulvovaginal candidiasis (VVC) during their lifetime. Patients with recurrent or severe VVC warrant a screening test for diabetes mellitus.

  Postmenopausal: After menopause, most women experience some vaginal atrophy as estrogen levels fall. Incidence of atrophic vaginitis depends on how it is defined. Vulvovaginitis related to infection is much less common after menopause. Desquamative inflammatory vaginitis has an unknown etiology, but a Gram stain of culture often reveals streptococci. This is treated with intravaginal clindamycin cream. Postirritation vulvovaginitis may occur in women undergoing pelvic irradiation for cancer.

• Internationally: Bacterial vaginosis is the most common cause of vaginitis in women of childbearing age, with prevalence of 50-60% across the globe.

  Trichomoniasis affects 180 million women worldwide.

Mortality/Morbidity: No mortality has been documented primarily from vulvovaginitis.

• Premenarchal: Persistent vulvovaginitis in children is sometimes mistaken for an infection rather than for a foreign body. Labial adhesion, possibly to the point of occlusion of the vaginal orifice, may occur as an isolated finding, be secondary to urinary tract infections (UTIs), or be secondary to vulvovaginitis. These adhesions usually do not cause long-term problems.

• Childbearing age: A variety of complications has been associated with bacterial vaginosis including the following:
  • Pelvic inflammatory disease

  • Increased incidence of abdominal pain, uterine bleeding, and uterine and adnexal tenderness

  • Increased complications of pregnancy, especially premature delivery, chorioamnionitis, postpartum endometritis, and ectopic pregnancy

  Candidal vulvovaginitis may develop into chronic or recurrent candidal infection related to the following:

  • Diabetes mellitus

  • Oral contraceptive (OCP) use

  • Antibiotic use

  • Immunodeficiency

  • Tight-fitting undergarments

  Some authors have suggested that T vaginalis, being sexually transmitted organisms, may act as vectors for other types of infections. The organism can be identified in 30-40% of male sexual partners of infected women, although carriage in men is self-limited and transient.

• Postmenarchal: Vaginal bleeding may occur from the thin mucosa. Dyspareunia may also occur as a complication.

Race:

• Premenarchal: Significance of race is not clearly defined.

• Childbearing age: One study found Trichomonas species to be 3 times more prevalent in black individuals than in white individuals. Bacterial vaginosis does not seem to have any significant racial variation.

Sex: Vulvovaginitis does not occur in males. Males may be carriers of G vaginalis and T vaginalis.

Age:

• Premenarchal: Vulvovaginitis predominately affects school-aged children.

• Childbearing age
  • Trichomonas species can occur in any age group, yet it is most common in adolescents and women in their 20s, peaking in those aged 20-24 years.

  • Bacterial vaginosis has a fairly equal distribution across all age groups up until menopause. Prevalence does not vary significantly with age.

  • Candida species infections are most common during childbearing years.

• Postmenarchal: Atrophic vaginitis may develop several years after menopause. Most women with vaginal atrophy do not develop atrophic vaginitis.

CLINICAL

Section 3 of 11

History: Different historical aspects should be ascertained depending on what vulvovaginitis category the patient may have.

• Premenarchal

• Wiping the anus from posterior to anterior, wearing tight-fitting synthetic undergarments, and using vaginal irritants such as bubble baths

• Recent upper respiratory infection or pharyngitis can lead to group A beta-hemolytic streptococci (GABHS) vaginitis.

• Vaginal pruritus, especially at night, suggests pinworm infection.

• Itching, soreness, bleeding, and vaginal discharge; bloody and foul-smelling discharge may suggest a vaginal foreign body.

• Vulvovaginitis may be secondary to sexual abuse of the child. Parents often equate vulvovaginitis with abuse, although this is not justified in most cases.

• Asymptomatic vaginal discharge often occurs in the months prior to menarche and represents a physiologic response to increasing estrogen levels.

• Skin conditions (ie, eczema, psoriasis, seborrhea) occasionally involve the vagina, and a history of these conditions should be sought.

• In obtaining a history of women in childbearing age, record a complete sexual history, last menstrual period, number of sexual partners, and methods of birth control. A new sexual partner increases the risk of STD and pregnancy. Inquire about antibiotics, high estrogen oral contraceptive pills, and any abdominal pain; ask about the patient's hygienic practices (daily use of panty liners and feminine products).

• Irritants such as soaps, baths, spermicides, perfumes, douches, and creams can cause vulvovaginitis. Tight-fitting, synthetic undergarments can increase moisture, exacerbating this condition.

• Vulvovaginitis is usually related to infections secondary to Gardnerella, Trichomonas, or Candida species. Vaginal discharge, pruritus, burning sensation, foul-smelling odor, superficial dyspareunia, and dysuria may be the presenting complaint. With candidiasis, the patient may describe a thick, white, cottage cheese–like discharge associated with pruritus.

• In postmenopausal women, inquire about vaginal bleeding or spotting, dysuria, pruritus, watery discharge, or dyspareunia and decreased sexual activity.

Physical:

• Premenarchal

• Genital examination of a prepubertal girl may produce a great deal of anxiety. Explaining the examination to the child and parent, keeping the parent at the patient's side, and explaining the difference between allowing a physician or anyone else to examine her genitals may make the examination less traumatic. Sedation rarely is necessary.

• Cultures are not necessary most of the time. History and physical examination should indicate when to obtain a culture from the patient.

• Childbearing age

• A complete pelvic examination is needed to evaluate possible upper genital tract infection.

• Specific clinical descriptions and physical examination findings have been described for each of the 3 etiologies (Gardnerella, Trichomonas, and Candida species), yet these often overlap.

• More than one infection may be present simultaneously. This usually necessitates additional diagnostic testing to confirm the diagnosis.

• Pathologic vaginal discharge may be odor producing and may adhere to the vaginal walls, unlike odorless physiologic discharge found in the dependent areas of the vagina.

• Bacterial vaginosis typically presents with an unpleasant fishy-smelling discharge that is more noticeable after unprotected intercourse. A thin, gray-white vaginal discharge that is homogeneous may adhere to the vaginal walls and be present at the introitus. Pruritus and inflammation are unusual in bacterial vaginosis. The absence of inflammation is the basis for the term vaginosis rather than vaginitis.

• Trichomonal infection may be asymptomatic or may produce a profuse, frothy, yellow-gray, homogenous discharge. This discharge may adhere to the vaginal walls and may not be present at the vaginal introitus. In contrast to bacterial vaginosis, vulvar and vaginal erythema and edema with Trichomonas species often are present. Punctate hemorrhages may be visible on the vagina and cervix (2% of cases).

• Candida species infection typically is found as an isolated infection, heralded by pruritus. A thick, odorless, white, cottage cheese–like discharge often is found adhering to the vagina. Erythema, edema, and excoriation may be present. Dysuria and urinary frequency occasionally may be present.

• Postmenarchal

• Vaginal mucosa is thin with diffuse erythema, occasional petechiae or ecchymoses, and few or no vaginal folds.

• Hair loss may occur over the mons and labia majora.

• Loss of rugae may occur.

• Thinned mucosa may become friable.

Causes:

• Premenarchal

• Nonspecific - No defined etiologic agent or poor perineal hygiene

• Chemical irritants (eg, bubble baths, lotions)

• Vaginal foreign bodies

• Pinworm infection

• GABHS infection

• Skin conditions - Eczema, psoriasis, seborrhea

• Etiologies usually associated with women of childbearing age - Bacterial vaginosis, Trichomonas species, Candida species, and gonorrhea (many of these are associated with sexual abuse)

• Childbearing age

• Sexual contact especially with multiple sexual contacts

• No method of birth control

• History of STD

• Bacterial or fungal infections such as G vaginalis (bacterial vaginosis), Candida species, and Trichomonas species

• Chemical irritants

• Postmenarchal - Atrophic vaginitis (most common cause of vulvovaginitis in postmenarchal women)

DIFFERENTIALS

Section 4 of 11

Candidiasis
Dermatitis, Atopic
Dermatitis, Contact
Dermatitis, Exfoliative
Gonorrhea
Herpes Simplex
Pediatrics, Child Abuse
Pediatrics, Child Sexual Abuse
Pediatrics, Foreign Body Ingestion
Pediatrics, Urinary Tract Infections and Pyelonephritis
Pelvic Inflammatory Disease
Trichomoniasis
Vaginitis

WORKUP

Section 5 of 11

Lab Studies:

• Laboratory evaluation, if indicated, for a patient with vulvovaginitis consists of checking vaginal pH, performing microscopy, and obtaining a culture.

• Measurement of vaginal pH is the single most important finding that drives the diagnostic process and should always be determined. Vaginal pH can be tested using a narrow-range pH paper. A pH above 4.5 suggests infections such as bacterial vaginosis or trichomoniasis (pH 5-6) and helps to exclude candidal vulvovaginitis (pH 4-4.5).

• A wet preparation and/or mount can be prepared by placing a drop of vaginal secretion on a slide with a drop of saline and viewing the slide under a microscope. This can be used to look for candidal buds or hyphae, motile trichomonads, epithelial cells studded with adherent coccobacilli (clue cells), and polymorphonuclear cells. The saline should be at room temperature, and microscopy should be performed within 10-20 minutes to reduce the possibility of loss of any trichomonads.

• A potassium hydroxide (KOH) preparation is prepared by placing a drop of vaginal secretion on a slide with a drop of 10-20% KOH and using a coverslip to protect the microscope lens. This is particularly useful in diagnosis of candidal vaginitis. Smelling ("whiffing") the slide immediately after applying KOH is useful for detecting the fishy (amine) odor of bacterial vaginosis. Diagnostic cards, such as Femcard, are available commercially, providing a rapid test in confirming the diagnosis of bacterial vaginosis. These are especially useful for practitioners who are unable to perform microscopy. The test detects the presence of elevated vaginal pH level and increased amine with a sensitivity of 87% and a specificity of 92%.

• Vaginal culture may help to diagnose the exact etiology in a bacterial or fungal infection. Cultures are not useful for Trichomonas species infections and bacterial vaginosis. Gardnerella species can be cultured as typical flora in many women who are asymptomatic; therefore, a culture that is reported as positive for Gardnerella species should not be assumed to indicate a vaginal infection that requires treatment unless the woman also has complaints of vaginitis.

• Workup in prepubertal girls is as follows:

• For most patients, laboratory evaluation does not lead to an etiologic diagnosis; thus, lengthy evaluations are not indicated. A complete history and physical examination are all that are required.

• Culture for GABHS and a urine culture may be appropriate in children.

• For patients in whom abuse is suspected, perform cultures for gonorrhea and chlamydia.

• If a vaginal foreign body is suspected, irrigating the vagina with saline may dislodge certain types of foreign bodies (eg, toilet paper). An examination sometimes requires conscious sedation or general anesthesia.

• If pinworms are suspected, the infection may be diagnosed by direct visualization of the worm by the parent or physician (typically at night). Another method is to use transparent tape applied to the perineum in the morning in hopes of collecting the eggs of Enterobius vermicularis (ie, pinworm), which then can be observed under low-power microscopy.

• Workup in females of childbearing age is as follows:

• The correct diagnosis is typically obtained by checking pH and performing microscopy. Vaginal pH of a physiologic discharge caused by Candida species is 4-4.5. Bacterial vaginosis is associated with a pH of 5-6. Trichomonas species infection has the highest pH, generally 6-7.

• In bacterial vaginosis, the presence of clue cells is the single most reliable predictor of bacterial vaginosis. Clue cells are vaginal epithelial cells studded with adherent coccobacilli that are best appreciated at the edge of the cell. At least 20% of the epithelial cells on wet mount should be clue cells.

• In 80-90% of women with trichomonal infections, a wet preparation or mount viewed under high power reveals many leucocytes and mobile trichomonads. Consider screening for other STDs such as syphilis, gonorrhea, and chlamydia.

• In candidal infections, KOH preparation may reveal budding filaments, mycelia, or pseudohyphae. A fungal culture may be used if the diagnosis is uncertain. Microscopy for candidal disease has an estimated sensitivity of 65%. For recurrent or severe vulvovaginitis, consider a screening test for diabetes, either serum glucose or urine dip for glucose.

• Perform a pregnancy test on all women of reproductive age.

• Workup in postmenopausal women is as follows:

• History and physical examination generally provide sufficient information to diagnose atrophic vaginitis.

• Vaginal pH, if performed, generally is 6-7.

• A wet mount or preparation may demonstrate inflammatory cells and an increased number of parabasal epithelial cells.

• Culture and a KOH preparation usually are unrewarding.

TREATMENT

Section 6 of 11

Prehospital Care:

• Prehospital care rarely is needed.

• Some women with recurrent candidal infections opt for treatment with over-the-counter (OTC) medications that generally are highly effective. Preparations for intravaginal administration of butoconazole, clotrimazole, miconazole, and tioconazole are available OTC. Self-medication with OTC preparations should be advised only for women who have been diagnosed previously with VVC and who have a recurrence of the same symptoms. Any woman whose symptoms persist after using an OTC preparation or who has a recurrence of symptoms within 2 months should seek medical care. Unnecessary or inappropriate use of OTC preparations is common and can lead to delay of treatment of other etiologies of vulvovaginitis that could result in adverse clinical outcomes.

Emergency Department Care:

• No specific ED care is needed.

• If sexual abuse of a child is suspected, call upon further resources, such as a social work and child welfare agency.

• Medical treatment should be tailored to the suspected pathogen.

Consultations:

• Consultations are not necessary for most patients.

• Suspected child sexual abuse must be reported to the child welfare agency and police. Strongly consider consultation with a clinician experienced in the area of child abuse, if available.

• A patient with a vaginal foreign body that is difficult to observe or remove may require sedation or referral to a gynecologist for examination under general anesthesia.

• Patients with infections that are difficult to treat or that are recurrent occasionally require gynecologic consultation.

MEDICATION

Section 7 of 11

Treatment should be aimed at bacterial, parasitic, or fungal infection.

Drug Category: Antibiotics -- Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the clinical setting.
A 7-day oral course yields a 90% cure, and single oral dose therapy yields an 80% cure. If single oral dose therapy is ineffective, either administer a second oral dose in 48 hours or initiate weeklong therapy. Some patients prefer intravaginal medication.

Drug Name	Penicillin VK (Veetids, Beepen-VK) -- Indicated when the offending organism is group A streptococci. Inhibits biosynthesis of cell wall mucopeptide and is effective during active replication. Inadequate concentrations may produce only bacteriostatic effects.
Adult Dose	500 mg PO q6h for 10 d
Pediatric Dose	<13 years: 40-50 mg/kg/d PO divided tid/qid, not to exceed 3 g/d Adolescents: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Probenecid can increase penicillin effectiveness by decreasing its clearance; conversely, coadministration of tetracyclines can decrease penicillin effectiveness
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Caution in impaired renal function

Drug Name	Erythromycin (EES, E-Mycin, Ery-Tab) -- DOC for penicillin-allergic patients with infections caused by susceptible strains of microorganisms, including group A streptococci. Inhibits RNA-dependent protein synthesis, possibly by stimulating dissociation of peptidyl tRNA from ribosomes, which inhibits bacterial growth. In children, age, weight, and severity of infection determine proper dosage. When bid dosing is desired, half-total daily dose may be taken q12h. For more severe infections, double the dose.
Adult Dose	250 mg erythromycin stearate/base, or 400 mg ethylsuccinate PO q6h 1 h ac or 500 mg q12h for 10 d
Pediatric Dose	30-50 mg/kg/d PO divided q6-8h for 10 d, not to exceed 2 g/d; double dose for severe infections
Contraindications	Documented hypersensitivity; hepatic impairment
Interactions	Coadministration may increase toxicity of theophylline, digoxin, carbamazepine, and cyclosporine; may potentiate anticoagulant effects of warfarin; coadministration with lovastatin and simvastatin increases risk of rhabdomyolysis
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Caution in liver disease; estolate formulation may cause cholestatic jaundice; GI adverse effects are common (administer doses pc); discontinue use if nausea, vomiting, malaise, abdominal colic, or fever occurs

Drug Name	Metronidazole (Metro-Gel, Noritate) -- Imidazole ring-based antibiotic active against various anaerobic bacteria and protozoa. Indicated for treatment of bacterial vaginosis (formerly referred to as Haemophilus vaginitis, Gardnerella vaginitis, nonspecific vaginitis, Corynebacterium vaginitis, anaerobic vaginosis).
Adult Dose	2 g PO once or 500 mg PO bid for 7 d Alternatively: Metronidazole gel 0.75%, 1 applicatorful (5 g) intravaginally qd for 5 d effective as oral metronidazole Pregnancy: 250 mg PO tid for 7 d or 2 g PO once; use during pregnancy after first trimester only if clearly indicated
Pediatric Dose	15-30 mg/kg/d PO divided bid for 7 d; not to exceed 500 mg or 40 mg/kg PO once Alternatively: Insert 1 applicatorful as in adults
Contraindications	Documented hypersensitivity; avoid during first trimester of pregnancy
Interactions	Cimetidine may increase toxicity of metronidazole; may increase effects of anticoagulants; may increase toxicity of lithium and phenytoin; avoid alcohol during treatment and 24 h after that
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in hepatic disease; monitor for seizures and development of peripheral neuropathy; known or previously unrecognized vaginal candidiasis may present more prominent symptoms during metronidazole vaginal gel therapy; more than 6% of patients have developed symptomatic candidal vaginitis during or immediately after therapy

Drug Name	Clindamycin (C/T/S, Clinda-Derm, Cleocin HCl) -- Useful as treatment against serious skin and soft tissue infections caused by most staphylococcal strains. Inhibits bacterial protein synthesis by inhibiting peptide chain initiation at the bacterial ribosome, where it preferentially binds to the 50S ribosomal subunit, causing bacterial growth inhibition. Has a 90% cure rate and is used as an alternative to metronidazole.
Adult Dose	Clindamycin cream 2%: 1 applicatorful (5 g)intravaginally hs for 7 d Alternatively: Administer 300 mg PO bid for 7 d or clindamycin ovules 100 g intravaginally qhs for 3 d
Pediatric Dose	20-30 mg/kg/d PO divided tid/qid for 7 d
Contraindications	Documented hypersensitivity; regional enteritis; ulcerative colitis; hepatic impairment
Interactions	None reported
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Avoid contact with eyes; vaginal cream contains ingredients that cause burning and irritation of the eye; in event of accidental contact, rinse eye with copious amounts of cool tap water; use of clindamycin vaginal cream may result in overgrowth of nonsusceptible organisms, particularly yeasts, in vagina; clindamycin cream and ovules are oil-based and might weaken latex condoms and diaphragms; antibiotic-associated colitis has been reported with both oral and topical clindamycin

Drug Category: Corticosteroids -- These agents are used to treat extreme vaginal pruritus. Cream is for symptomatic relief, especially in pediatric vulvovaginitis.
These agents are adrenocorticosteroid derivatives incorporated into a vehicle suitable for application to skin or external mucous membranes.

Drug Name	Hydrocortisone (Cortef Feminine Itch, Delcort) -- DOC because of its mineralocorticoid activity and glucocorticoid effects. Primary therapeutic effects of topical corticosteroids are from their anti-inflammatory activity, which is nonspecific (ie, they act against most causes of inflammation including mechanical, chemical, microbiological, immunological). Do not use very high or high-potency agents on the face, groin, or axilla.
Adult Dose	Apply sparingly bid to vagina in affected areas
Pediatric Dose	Apply as in adults
Contraindications	Documented hypersensitivity; viral, fungal, and bacterial skin infections
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Prolonged use, applying over large surface areas, applying potent steroids, and using occlusive dressings may increase systemic absorption of corticosteroids and may cause Cushing syndrome, reversible HPA-axis suppression, hyperglycemia, and glycosuria

Drug Category: Antifungal agents -- These agents are used to treat candidal vulvovaginitis. Topical azole antifungals achieve cure rates of 85-95%. Nystatin demonstrates a 75-80% cure rate. Oral fluconazole has a cure rate comparable to topical azole antifungals. It may be preferred by patients because of the ease of one-time dosing.
Intravaginal and topical therapies with a variety of antifungals, such as clotrimazole, miconazole, terconazole, and tioconazole, are highly effective. Many of the preparations are now available OTC. 1-, 3-, and 7-day regimens can be used. Cure rates of 90% are reported with longer courses.

Drug Name	Clotrimazole (Mycelex-7), butoconazole (Femstat), miconazole (Monistat Vaginal) -- Broad-spectrum antifungal agents that inhibit yeast growth by altering cell membrane permeability, which causes fungal cell death.
Adult Dose	1-d therapy: Clotrimazole 500-mg tab: Insert 1 applicatorful intravaginally once Tioconazole 6.5% ointment: Insert 5 g, 1 applicatorful, intravaginally once 3-d therapy: Clotrimazole 100-mg tab: Insert 2 tab intravaginally qhs for 3 d Butoconazole 2% cream: Insert 5 g, 1 applicatorful, intravaginally qhs for 3 d Miconazole 200-mg vaginal suppository: Insert 1 supp intravaginally qhs for 3 d Terconazole 0.8% cream: Insert 5 g, 1 applicatorful, intravaginally qhs for 3 d Terconazole 80-mg vaginal supp: Insert 1 supp intravaginally qhs for 3 d 7-d therapy: Clotrimazole applicator: Insert 5 g, 1 applicatorful, of 1% vaginal cream intravaginally qhs for 7-14 d Clotrimazole vaginal tab: Insert 1 tab (100 mg) intravaginally qhs for 7 d Miconazole 2% cream: Instill 5 g, 1 applicatorful, intravaginally qhs for 7 d Miconazole 100-mg vaginal supp: Insert 1 supp intravaginally qhs for 7 d Terconazole 0.4% cream: Insert 5 g, 1 applicatorful, intravaginally for 7 d Terconazole tab: Insert 2 tab (100 mg each) intravaginally qhs for 3 d or a 500-mg tab intravaginally once Terconazole 1% vaginal cream: Apply to external genitalia bid Ketoconazole 2% cream: Rub gently into affected area qd/bid Nystatin 100,000-U tab: Insert 1 tab qhs for 2 wk
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	If irritation or sensitization occurs, discontinue use; chronic or recurrent candidiasis may be a symptom of unrecognized diabetes mellitus or a damaged immune system (including HIV infection); persistently resistant infections may be re-infections, thus evaluate sources of re-infection; if lack of response, repeat microbiologic studies to confirm diagnosis and exclude other pathogens before re-instituting antifungal therapy; do not use creams in mouth or eyes; no well-controlled studies have been performed during first trimester of pregnancy; these products may compromise condoms and diaphragms

Drug Name	Fluconazole (Diflucan) -- Synthetic oral antifungal (broad-spectrum bistriazole) that selectively inhibits fungal cytochrome P-450 and sterol C-14 alpha-demethylation. Consider ease of use, although direct cost may be a limiting factor. Do not recommend PO antifungals in pregnancy.
Adult Dose	150 mg PO once
Pediatric Dose	3-6 mg/kg PO qd for 14-28 d, depending on severity of infection
Contraindications	Documented hypersensitivity
Interactions	Levels may increase with hydrochlorothiazides; levels may decrease with chronic coadministration of rifampin; coadministration of fluconazole may decrease phenytoin concentrations; may increase concentrations of theophylline, tolbutamide, glyburide, and glipizide; effects of anticoagulants may increase with fluconazole coadministration; increases in cyclosporine concentrations may occur when administered concurrently
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Monitor closely if rashes develop and discontinue drug if lesions progress; may cause clinical hepatitis, cholestasis, and fulminant hepatic failure (including death) with underlying medical conditions such as AIDS or a malignancy and while taking multiple concomitant medications; not recommended for women who are breastfeeding

Drug Category: Estrogens -- These agents are used in treatment of atrophic vaginitis in postmenopausal women. Oral estrogen replacement also is effective and has other health benefits. Oral estrogen therapy generally should be initiated by a primary care physician rather than an ED physician.

Drug Name	Conjugated estrogens (Premarin) -- Several topical steroid preparations are available, including equine estrogen, estradiol, and dienestrol. Estrogens are indicated for atrophic vaginitis and atrophic urethritis associated with menopause.
Adult Dose	0.3-1.25 mg PO qd, depending on tissue response of patient Topical: Insert 2-4 g, 0.5-1 applicatorful intravaginally qhs Recommendation: Cyclical administration consisting of 3 wk of daily estrogen and 1 wk off
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; known or suspected pregnancy; breast cancer; undiagnosed abnormal genital bleeding; active thrombophlebitis or thromboembolic disorders; history of thrombophlebitis, thrombosis, or thromboembolic disorders associated with previous estrogen use (except when used in treatment of breast or prostatic malignancy)
Interactions	May reduce hypoprothrombinemic effects of anticoagulants; coadministration of barbiturates, rifampin, and other agents that induce hepatic microsomal enzymes may reduce estrogen levels; pharmacologic and toxicologic effects of corticosteroids may occur as a result of estrogen-induced inactivation of hepatic P450 enzyme; loss of seizure control has been noted when administered concurrently with hydantoins
Pregnancy	X - Contraindicated in pregnancy
Precautions	Certain patients may develop undesirable manifestations of excessive estrogenic stimulation, such as abnormal or excessive uterine bleeding or mastodynia; estrogens may cause some degree of fluid retention (exercise caution); prolonged unopposed estrogen therapy may increase risk of endometrial hyperplasia

Drug Category: Anthelmintics -- These agents are used to treat parasitic infections. Parasite biochemical pathways are sufficiently different from the human host to allow selective interference by chemotherapeutic agents in relatively small doses.

Drug Name	Mebendazole (Vermox) -- Indicated drug to treat pinworm. Kills worms by selectively and irreversibly blocking glucose uptake and other nutrients in the susceptible adult intestine where helminths dwell.
Adult Dose	100 mg PO once Alternatively: Administer 100 mg PO bid on 3 consecutive days; second course may be administered if patient is not cured within 3-4 wk
Pediatric Dose	<2 years: Not established >2 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Carbamazepine and phenytoin may increase mebendazole metabolism, decreasing its efficacy; conversely, cimetidine may increase mebendazole levels
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Avoid in pregnancy, especially during first trimester; may need to adjust dose in hepatic impairment

Drug Name	Pyrantel (Pin-Rid, Pin-X, Reese Pinworm) -- Used as an alternative to mebendazole; a depolarizing neuromuscular blocking agent that inhibits cholinesterases, resulting in spastic paralysis of the worm. Active against E vermicularis (ie, pinworm) and Ascaris lumbricoides (ie, roundworm). Also effective against Ancylostoma duodenale (ie, hookworm). Purging is not necessary; may be taken with milk or fruit juices.
Adult Dose	11 mg/kg (5 mg/lb) PO not to exceed 1 g once without regard to ingestion of food or time of day
Pediatric Dose	<2 years: Not established >2 years: Administer as in adults
Contraindications	Documented hypersensitivity; hepatic disease
Interactions	In ascariasis, pyrantel and piperazine are mutually antagonistic and should not be used concomitantly; theophylline serum levels may increase in pediatric patients following pyrantel pamoate administration
Pregnancy	D - Unsafe in pregnancy
Precautions	Caution in liver impairment, anemia, and malnutrition

Drug Category: Estrogen receptor antagonists -- These agents competitively bind to estrogen receptor, producing a nuclear complex that decreases DNA synthesis and inhibits estrogen effects.

Drug Name	Tamoxifen (Nolvadex) -- May be used for women who are very concerned about estrogen exposure. Known to have both estrogen antagonist and agonist effects, depending on target tissue.
Adult Dose	10-20 mg PO bid
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	May exacerbate hepatotoxic effects of allopurinol; may increase cyclosporine serum levels; increases anticoagulant effects of warfarin; aminoglutethimide reduces serum concentration of tamoxifen; cyclophosphamide, methotrexate, and 5-FU increase thrombotic risk of tamoxifen
Pregnancy	D - Unsafe in pregnancy
Precautions	Caution in leukopenia, thrombocytopenia, and hyperlipidemia; decreased visual acuity, corneal changes, and retinopathy may occur with > 1 y of use; may induce ovulation

FOLLOW-UP

Section 8 of 11

Further Outpatient Care:

• Premenarchal: Most patients do not have an identifiable etiologic agent for infection. Therefore, treatment aims at improving perineal hygiene and decreasing moisture.

• A period of supervised defecation may be helpful, stressing the need to wipe thoroughly and anteriorly to posteriorly. Stress the importance of wearing loose-fitting, cotton undergarments. Stress the need to avoid vaginal irritants such as bubble baths and creams. A sitz bath with baking soda may be helpful. Thoroughly drying the perineum and avoiding unnecessary moisture, such as prolonged exposure to a wet bathing suit, may be helpful. If these methods are unsuccessful, perform a vaginal culture.

• If a bacterial etiology seems likely, consider a course of broad-spectrum antibiotics.

• Topical estrogen cream for up to 2 weeks may help if local measures do not work. If pruritus is severe, a short trial of a topical steroid such as 0.5% hydrocortisone may be used.

• Remove vaginal foreign bodies, possibly with the use of sedation.

• Streptococcal infections respond to penicillin or erythromycin.

• Treat pinworms with mebendazole or pyrantel pamoate. The entire family may need to be treated to eradicate the infection.

• Treat STDs appropriately using pediatric doses. All STDs should prompt an evaluation for sexual abuse.

• Childbearing age: In women of childbearing age, treat irritant causes of vulvovaginitis by removing the offending agent.

• Perform a pregnancy test, since the treatments may be contraindicated in pregnancy.

• Bacterial vaginosis is treated in nonpregnant women with metronidazole, orally or intravaginally. Several dosing regimens are available. A possible choice is to use single-dose treatment. Clindamycin may be used as an alternative. Treatment of sexual partners generally is not beneficial. Follow-up visits are unnecessary if symptoms resolve.

• Because recurrence of bacterial vaginosis is not unusual, women should be advised to return for additional therapy if symptoms recur. Another recommended treatment regimen may be used to treat recurrent disease. No long-term maintenance regimen with any therapeutic agent is recommended.

• Trichomonas species infection is treated very effectively with metronidazole in nonpregnant women. Several dosing regimens are available. Sexual partners should be treated, even if asymptomatic, although re-infection rate appears to be low even if the partner is not treated. Patients should be instructed to avoid sex until they and their sex partner are cured (ie, when therapy has been completed and patient and partner are asymptomatic [in the absence of a microbiologic test of cure]). Effective treatment during pregnancy is problematic because of concerns about possible teratogenic effects during the first trimester. Follow-up is unnecessary for men and women who become asymptomatic after treatment or who are initially asymptomatic. If treatment failure occurs with either regimen, the patient should be retreated with metronidazole 500 mg twice a day for 7 days. If treatment failure occurs again, the patient should be treated with a single, 2-g dose of metronidazole once a day for 3-5 days.

• Candida species infection can be treated successfully with a variety of topical antifungals. Many are now available over-the-counter with 1-, 3-, 5-, and 7-day dosing regimens. Oral therapy with single-dose fluconazole is effective. Recurrent and chronic infections are best treated with low-dose prophylactic ketoconazole.

• Postmenarchal: In postmenopausal women with atrophic vaginitis, therapy focuses on topical estrogen replacement. Some women on oral estrogen replacement still develop atrophic vaginitis.
  • A variety of topical estrogen preparations is available for intravaginal, once-a-day use, generally for 1-2 weeks. When symptoms improve, frequency may be decreased to once or twice per week.

  • Systemic estrogen absorption from the vagina seems to diminish as the vaginal epithelium matures. Tamoxifen may be used for women who are very concerned about estrogen exposure.

Complications:

• Pelvic inflammatory disease

• Intrauterine infections

• Chorioamnionitis

• Postpartum endometritis

• Vaginitis emphysematous

• Preterm labor

• Premature rupture of membranes

• Newborn infections

Prognosis:

• Premenarchal

• Improved hygiene and methods to decrease moisture may help 50% of these patients.

• If symptoms persist, consider the possibility of a foreign body.

• A course of antibiotics or topical estrogen occasionally helps.

• Streptococcal and pinworm infections respond promptly to antimicrobials.

• Childbearing age

• Bacterial vaginosis is cured with single-dose treatment in 80% of patients and with weeklong treatment in 90%.

• Cure rates for Trichomonas species infection are higher than for bacterial vaginosis.

• Candidal treatment with topical or oral therapy yields a cure rate of 90%. Approximately 5% of women have difficult-to-treat infections. Recurrence is common.

Patient Education:

• Premenarchal: Focus patient education on improved perineal hygiene and on avoiding irritants.

• Childbearing age: Patient education should review the sexually transmitted nature of Trichomonas species and, possibly, bacterial vaginosis.

• Postmenopausal: Patient education should stress the treatable nature of atrophic vaginitis; it does not have to be a natural consequence of aging.

• For excellent patient education resources, visit eMedicine's Pregnancy and Reproduction Center, Yeast and Fungal Infections Center, Women's Health Center, and Parasites and Worms Center. Also, see eMedicine's patient education articles Vaginal Infections, Candidiasis (Yeast Infection), Understanding Vaginal Yeast Infection Medications, Birth Control Overview, href="http://www.emedicinehealth.com/articles/39063-1.asp" target="_blank">Birth Control FAQs, Female Sexual Problems, and Trichomoniasis.

MISCELLANEOUS

Section 9 of 11

Medical/Legal Pitfalls:

• Failure to consider child sexual abuse in the correct clinical context

• Failure to appreciate that endometrial and/or endocervical lesions also may be etiologies of vaginal spotting after menopause

TEST QUESTIONS

Section 10 of 11

CME Question 1: Which of the following statements regarding vulvovaginitis in a premenarchal child is correct?

A: It is highly suggestive of sexual abuse.
B: It mandates a bimanual and speculum examination.
C: It is most common in the first year of life.
D: It responds well to topical antifungal cream.
E: It is usually nonspecific (ie, culture results are negative or polymicrobial).

The correct answer is E: Vulvovaginitis in a premenarchal child is usually nonspecific.

CME Question 2: Which of the following statements regarding vulvovaginitis during the childbearing years is correct?

A: In most patients, it is transmitted sexually.
B: It can be treated effectively with single-dose medications in the ED.
C: It is diagnosed using findings from routine culture.
D: It can be diagnosed correctly by assessing information from history alone.
E: It typically is related to poor perineal hygiene.

The correct answer is B: Vulvovaginitis during childbearing years can be treated effectively with single-dose medications in the ED.

Pearl Question 1 (T/F): Chronic or severe candidal vaginitis may indicate the clinical condition of antibiotic resistance.

The correct answer is False: Chronic or severe candidal vaginitis may indicate diabetes mellitus; although this condition rarely presents with candidal vaginitis, undiagnosed or poorly controlled diabetes may aggravate candidal infections.

Pearl Question 2 (T/F): The following etiologies of vaginitis can be treated with single-dose therapy: Trichomonas species, bacterial vaginosis, and Candida species.

The correct answer is True: Convenient and effective single-dose regimens are available for Trichomonas species, bacterial vaginosis, and Candida species.

Pearl Question 3 (T/F): When metronidazole is used for treatment (eg, of vaginitis), advise patients about interaction with alcohol.

The correct answer is True: Metronidazole should not be used with alcohol, since this may result in very unpleasant adverse effects.

Pearl Question 4 (T/F): In women of childbearing age, vaginal pH, wet mount, and potassium hydroxide (KOH) preparation are simple and inexpensive tests that help aid in the correct diagnosis.

The correct answer is True: A vaginal pH, wet mount, and KOH preparation are easy to perform, inexpensive, and effective methods to use in diagnosing vulvovaginitis in women of childbearing age.

BIBLIOGRAPHY

Section 11 of 11

• Braverman PK: Prepubertal vulvovaginitis. In: Long SS, Pickering LK, Prober CG, eds. Principles and Practice of Pediatric Infectious Diseases. 2nd ed. 2002.
• Carey JC, Klebanoff MA, Hauth JC, et al: Metronidazole to prevent preterm delivery in pregnant women with asymptomatic bacterial vaginosis. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. N Engl J Med 2000 Feb 24; 342(8): 534-40[Medline].
• Gabbe SG: Vaginal infections. In: Obstetrics - Normal and Problem Pregnancies. 4th ed. 2002.
• Johns Hopkins: Diagnostic features and management of vaginal infections. In: The Harriet Lane Handbook: A Manual for Pediatric House Officers. 17th ed. 2005.
• Marrazzo J: Vulvovaginal candidiasis. BMJ 2002 Sep 14; 325(7363): 586[Medline].
• Owen MK, Clenney TL: Management of vaginitis. Am Fam Physician 2004 Dec 1; 70(11): 2125-32[Medline].
• Sobel JD: Vaginitis, vulvitis, cervicitis and cutaneous vulval lesions. In: Infectious Diseases. 2nd ed. Cohen & Powderly; 2004.
• Workowski KA, Levine WC: Centers for Disease Control and Prevention. Sexually Transmitted Diseases Treatment Guidelines. 2002[Full Text].

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