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Essentials of Diagnosis
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- Intense vulvar pruritus
- A white vaginal discharge
- Vulvar erythema
- Filaments and spores in vaginal discharge can be seen in saline (“wet prep”) and KOH preparations
- The gold standard for diagnosis is a vaginal culture
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Approximately 75% of women experience an episode of vulvovaginal candidiasis during their lifetime. Candida albicans, the most common Candida species, causes symptomatic vulvovaginitis in approximately 90% of the cases. C albicans frequently inhabits the mouth, throat, large intestine, and vagina. Clinical infection is dependent on considerable growth and colonization and may be associated with a systemic disorder (diabetes mellitus, HIV, obesity), pregnancy, medication (antibiotics, corticosteroids, oral contraceptives), and chronic debilitation.
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Nonabsorbent undergarments should be avoided. The vulva and vaginal area should be kept dry. Controlling any underlying metabolic illnesses, especially diabetes, can prevent candidal growth. Even when diabetes is not present, a low-sugar diet is recommended, as the glucose in a vaginal discharge may promote the growth of the yeast. Complicating medications, especially antibiotics, estrogen, or oral contraceptive, should be discontinued if possible. Some experts recommend administering a prophylactic dose of an antifungal medication simultaneous to every antibiotic administration.
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Vulvovaginal candidiasis presents with intense vulvar pruritus; a white, cheesy vaginal discharge; and vulvar erythema. A burning sensation may follow urination, particularly if there is excoriation of the skin from scratching. Widespread involvement of the skin adjacent to the labia may suggest an underlying systemic illness. The labia minora may be erythematous and edematous.
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Diagnosis is based on a normal vaginal pH ≤4.5 and microscopic evaluation of vaginal secretions both in a saline preparation (wet prep) and mixed with 10% KOH solution. Identification of C albicans requires detections of filamentous forms (pseudohyphae) of the organism (Fig. 39–5). Spores may be present as well, but the presence of spores alone may indicate a Candida glabrata infection. The gold standard for diagnosis is a vaginal culture.
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Differential Diagnosis
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Genital herpes and localized provoked vulvodynia should be included in the differential diagnosis. Other causes of vaginal discharge are discussed later in this chapter.
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Complications include an entity called complicated vulvovaginal candidiasis, described in Table 39–10.
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The current medical treatment of candidal infection is by imidazoles, fungistatic agents that interfere with the production of the sterol of the cell wall (Table 39–11). These are available as topical creams, vaginal suppositories, and oral agents. Application of a topical steroid may be beneficial to the patient with severe vulvar itch or edema. In evaluating the patient with complicated candidal vulvovaginitis, underlying predisposing disease processes should be addressed. Additionally, cultures of the vagina should be taken to identify resistant strains. C glabrata and Candida tropicalis, which are detected with increasing frequency, require prolonged periods of treatment.
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Treatment regimens for complicated candidal vulvovaginitis include prolonging antifungal therapy for at least 2 weeks, consistent with the life cycle of yeast; self-medication for 3–5 days upon first evidence of symptoms; and prophylactic treatment for several days before menstruation or during antibiotic therapy. Oral administration of fluconazole 150 mg weekly for 6 months or itraconazole 100 mg daily for 6 months may reduce the frequency of recurrence to 10% during maintenance therapy. Liver function should be monitored during prolonged oral therapy. Treatment of the partner may be considered in cases of symptomatic balanitis.
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Gentian violet 1%, an aniline dye, has demonstrated effectiveness against C albicans and C glabrata when painted over vaginal surfaces once weekly. Boric acid compounded in a 600-mg suppository form, administered daily for 6 weeks, is also effective treatment for candidiasis and yeast infestation. Polyenes, such as nystatin, which is not absorbed in the gastrointestinal tract, may be taken orally to reduce intestinal colonization. Flucytosine may be administered in resistant cases.
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Recurrent disease may result from insufficient duration of therapy, recontamination, or resistant strains. Unfortunately, in 57% of patients, recurrences present within 6 months of discontinuation of prophylactic treatment.
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Essentials of Diagnosis
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- Homogeneous vaginal discharge
- Amine (fishy) odor when potassium hydroxide solution is added to vaginal secretions (commonly called the “whiff test”)
- Presence of clue cells (more than 20% of epithelial cells) on microscopy (Fig. 39–9)
- Vaginal pH >4.5
- Decrease in lactobacillus, small gram-variable rods, or curved gram-variable rods in gram-stained smear
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Bacterial vaginosis (BV), previously referred to as Gardnerella vaginitis, Haemophilus vaginitis, or nonspecific vaginitis, is the most common cause of symptomatic bacterial infection in reproductive-aged women in many countries. This condition is characterized by an alteration in the normal vaginal flora. The concentration of the hydrogen peroxide–producing lactobacillus decreases, and there is overgrowth of Gardnerella vaginalis, Mobiluncus spp., anaerobic gram-negative rods (Prevotella spp., Porphyromonas spp., Bacteroides spp.), and Peptostreptococcus spp. Whether bacterial vaginosis is a true sexually transmitted disease is controversial, although women who are not sexually active are rarely affected.
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Maintaining vaginal pH at a normal range may prevent recurrences. The potential benefit of lactobacillus intravaginal suppositories in restoring normal flora, and of acidifying vaginal douching, is being studied.
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Bacterial vaginosis presents as a “fishy” vaginal discharge, which is more noticeable after unprotected intercourse, due to the increased pH caused by the ejaculate. The patient complains of a milky, homogenous, malodorous, usually nonirritating discharge. The term vaginosis, rather than vaginitis, is used due to the absence of vaginal mucosal inflammation, such as presents in candidal infections.
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Two diagnostic scales are often used to diagnose bacterial vaginosis: Amsel's criteria and Nugent's score. According to Amsel's criteria, which establishes accurate diagnosis of bacterial vaginosis in 90% of affected women, 3 of the following 4 criteria must be met:
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Homogeneous vaginal discharge (color and amount may vary).
Amine (fishy) odor when potassium hydroxide solution is added to vaginal secretions (whiff test).
Presence of clue cells (>20% of epithelial cells) on microscopy. Clue cells are identified as numerous stippled or granulated epithelial cells (Fig. 39–9). This appearance is caused by the adherence of G vaginalis organisms to the edges of the vaginal epithelial cells.
Vaginal pH >4.5.
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Nugent's score is a Gram stain scoring system that provides a more sensitive (93%) and specific (70%) diagnosis than does the wet mount. The score is calculated by assessing for the presence of the following:
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Large gram-positive rods (lactobacillus morphotypes; decrease in lactobacillus, scored 0–4)
Small gram-variable rods (G vaginalis morphotypes, scored 0–4)
Curved gram-variable rods (Mobiluncus spp. morphotypes, scored 0–2)
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The total score ranges from 0 to 10. A score of 7–10 is consistent with bacterial vaginosis.
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Other Diagnostic Tests
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A culture of G vaginalis is not recommended as a diagnostic tool due to low specificity. Cervical Papanicolaou tests have low sensitivity. However, a DNA probe-based test may be clinically useful. Other commercially available tests for the diagnosis of BV include a card test for the detection of elevated pH and trimethylamine and proline aminopeptidase. The home-use of the VI-Sense panty liner has recently demonstrated effectiveness in the early detection of BV and of its recurrences after medical treatment.
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Differential Diagnosis
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Cervicitis and cervical neoplasia should be considered in the differential diagnosis of bacterial vaginosis.
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BV is reported to increase the risk of preterm delivery. It is unclear whether metronidazole treatment of asymptomatic pregnant women reduces the rates of preterm delivery and adverse pregnancy outcomes. In nonpregnant women, BV is associated with posthysterectomy vaginal cuff cellulitis, postabortion infection, and pelvic inflammatory disease.
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Treatment should be administered to symptomatic patients and considered in asymptomatic patients. Several treatment regimens exist (Table 39–12). Of importance, intravaginal administration of oil-based clindamycin reduces the effectiveness of condoms and diaphragms. For pregnant women, metronidazole 250 mg orally 3 times daily is recommended for 7 days or, alternatively, clindamycin 300 mg orally twice daily for 7 days. There is no evidence supporting the use of topical agents during pregnancy. Management strategies for recurrent vaginosis include use of condoms, longer treatment periods, prophylactic maintenance therapy, oral or vaginal application of yogurt containing lactobacillus acidophilus, intravaginal planting of other exogenous lactobacilli, and acidification of the vagina. Treatment of the male rarely helps in preventing recurrence in the female.
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Recurrence is frequent. Overgrowth of candida albicans after antibiotic treatment of bacterial vaginosis may be misinterpreted as recurrent bacterial vaginosis. A “universal” treatment of vulvovaginitis using a combination of clotrimazole and metronidazole in a single vaginal suppository has demonstrated effectiveness. Its use may prevent candida overgrowth.
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Trichomonas Vaginitis
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Essentials of Diagnosis
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- Profuse, frothy, greenish, and foul-smelling discharge
- pH of the vagina usually exceeding 5.0
- Vaginal erythema with multiple small petechiae (strawberry spots)
- Wet mount reveals an increase in polymorphonuclear cells and motile flagellates in 50–70% of zculture-confirmed cases
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Trichomonas vaginalis is a unicellular flagellate protozoan (Fig. 39–10) that is larger than polymorphonuclear leukocytes but smaller than mature epithelial cells. T vaginalis infects the lower urinary tract in both women and men. It is the most prevalent nonviral sexually transmitted disease in the United States. Nonsexual transmission is infrequent because large numbers of organisms are required to produce symptoms.
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A persistent vaginal discharge is the principal symptom with or without secondary vulvar pruritus. The discharge is profuse, extremely frothy, greenish, and at times foul-smelling. The pH of the vagina usually exceeds 5.0. Involvement of the vulva may be limited to the vestibule and labia minora. The labia minora may become edematous and tender. Urinary symptoms may occur; however, burning with urination is most often associated with severe vulvitis. Examination of the vaginal epithelium and cervix shows generalized vaginal erythema with multiple small petechiae, the so-called strawberry spots, which may be confused with epithelial punctation. Wet mount with normal saline reveals an increase in polymorphonuclear cells and characteristic motile flagellates in 50–70% of culture-confirmed cases.
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Vaginal trichomoniasis is usually diagnosed by microscopy of a wet mount preparation of vaginal secretions. Sensitivity is only 60–70%. Immediate evaluation is required, as the heat generated by the microscope light source causes the T vaginalis to discontinue its typical movements.
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Other Diagnostic Tests
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Other tests for trichomoniasis include immunochromatographic capillary flow dipstick technology and nucleic acid probing. Sensitivity exceeds 83%, and specificity is 97%. Results of the immunochromatographic Trichomonas Rapid Test are available in 10 minutes, and those of the nucleic acid probe test within 45. False-positive results do occur. Papanicolaou smears have a sensitivity of approximately 60% and also yield false-positive results. Culture is the most sensitive and specific method of diagnosis. In women in whom trichomoniasis is suspected but not confirmed by microscopy, vaginal secretions should be cultured for T vaginalis.
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Systemic therapy with metronidazole is the treatment of choice, because trichomonads sometimes present in the urinary tract system. Partners should be treated simultaneously, with intercourse avoided or a condom used until treatment is completed. US Centers for Disease Control and Prevention recommendations are presented in Table 39–13. If such treatments are not effective, sensitivity of a culture of T vaginalis to metronidazole and tinidazole should be determined. Side effects of metronidazole include nausea or emesis with alcohol consumption. Contraindications include certain blood dyscrasias (neutropenia) and central nervous system diseases. An oncogenic effect has been demonstrated in animals but not in humans. Resistance to metronidazole therapy is rare but is rising and can be confirmed in vitro.
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Trichomoniasis is associated with a number of perinatal complications and increased incidence in the transmission of HIV. Women with trichomoniasis should be evaluated for other sexually transmitted diseases, including Neisseria gonorrhoeae, Chlamydia trachomatis, syphilis, and HIV.
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Neisseria Gonorrhoeae
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Of women infected by N gonorrhoeae, 85% are asymptomatic. The glandular structures of the cervix, urethra, vulva, perineum, and anus are most commonly infected. In acute disease, patients present with a copious mucopurulent discharge and gram-negative diplococci within leukocytes. However, diagnosis should be confirmed with nucleic acid amplification or a culture from the endocervix, urethra, rectum, or mouth. An estimated 15–20% of women with lower tract disease develop upper genital tract disease with salpingitis, tubo-ovarian abscess, and peritonitis. Ectopic pregnancy and infertility are classic long-term consequences. If active infection is present during vaginal delivery, the newborn may develop conjunctivitis by contamination. Uncomplicated gonococcal infections of the cervix are treated with ceftriaxone 125 mg administered intramuscularly (IM) in a single dose. Single oral doses of cefixime 400 mg, ciprofloxacin 500 mg, ofloxacin 400 mg, or levofloxacin 250 mg are other recommended regimens. Quinolones are no longer recommended because some strains of N gonorrhoeae are quinolone-resistant. Spectinomycin 2 g IM in a single dose is an option for patients sensitive to cephalosporins. Empirical Treatment of C trachomatis should be considered, as this infection often coexists.
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Chlamydia Trachomatis
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The screening of sexually active young women for C trachomatis is important because some infections are asymptomatic, and some present with a mucopurulent cervicitis, dysuria, and/or postcoital bleeding. C trachomatis can be identified by culture (50–90% sensitivity), a direct fluorescent antibody (50–80% sensitivity), enzyme immunoassay (40–60% sensitivity), or, most recently, by using nucleic acid amplification tests (polymerase chain reaction or ligase chain reaction, 60–100% sensitivity). All tests have a specificity >99%. C trachomatis causes atypical cytologic findings on Papanicolaou smear and an ascending infection, salpingitis, in 20–40% of untreated patients. More than 50% of upper tract infections may be caused by C trachomatis, leading to tubal occlusion, ectopic pregnancy, or infertility. Untreated C trachomatis can also cause neonatal conjunctivitis. C trachomatis may present as LGV, which most commonly affects the vulvar tissues. Retroperitoneal lymphadenopathy may present. The initial lesion in LGV presents as a transient, painless vesicular lesion or shallow ulcer at the inoculation site. More advanced disease is characterized by anal or genital fistulas, stricture, or rectal stenosis. The disease is uncommon in the United States, but endemic in Southeast Asia and Africa.
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If C trachomatis is suspected or diagnosed, both the patient and partner should be treated. They should also be evaluated for concurrent gonococcal infections. Recommended therapy includes azithromycin 1 g orally in a single dose or doxycycline 100 mg orally twice daily for 7 days. Erythromycin base 500 mg orally 4 times daily for 7 days, ofloxacin 300 mg orally twice daily, and levofloxacin 50 mg once daily for 7 days are alternative regimens. Doxycycline, levofloxacin, and ofloxacin should be avoided in pregnancy and during lactation. Patients should abstain from intercourse for 7 days. Test of cure is required in cases of possible reinfection or persistent symptoms and during pregnancy. Repeat testing should be considered 3 weeks after treatment with erythromycin. Rescreening is recommended 3–4 months after treatment. For LGV, the recommended regimen is doxycycline 100 mg twice daily for 21 days.
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Mycoplasma hominis and Ureaplasma urealyticum also cause genital disease. Polymerase chain reaction is more sensitive than culture. Mycoplasma infections can cause infertility, spontaneous abortion, postpartum fever, salpingitis, and pelvic abscess, as well as nongonococcal urethritis in men. The most effective treatment is doxycycline 100 mg orally twice daily for 10 days.
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Conditions Mimicking Vaginitis
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Cervicitis due to chlamydial infection, cervical polyps, or cervical or vaginal cancer can cause a mucopurulent discharge and bleeding. Adenocarcinoma of the cervix may be missed by cytologic cervical screening and by colposcopy, becasue it generally develops in the endocervical canal rather than at the squamocolumnar junction. Excessive cervical ectropion may cause excessive discharge of cervical mucus from normal endocervical cells. Vaginal adenosis may cause the same type of clear, mucoid-type discharge without associated symptoms. Excessive desquamation of the vaginal epithelium may produce a diffuse gray-white pasty vaginal discharge, which may be confused with candidiasis. Vaginal pH is normal. Microscopic evaluation shows normal bacterial flora, mature vaginal squamae, and no increase in the number of leukocytes. Excessive but normal vaginal discharge should be treated with reassurance and, if required, with cryosurgery, carbon dioxide treatment, or loop conization of the cervix. Continuous use of a tampon should be avoided.
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Desquamative Inflammatory Vaginitis
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This rare condition of vaginitis should be considered in a patient with hard-to-treat vaginitis. The cause is unknown. Patients complain of a profuse purulent vaginal discharge, burning and pain upon urinating (dysuria) or intercourse (dyspareunia), and occasional spotting. Adherence of both vaginal walls, with gradual stenosis, is a common complication. The disease is a variant of the dermatologic disease lichen planus. In many cases, typical lichen planus layers are found on the skin, oral mucosa, and gums. Upon inspection, the vagina is found to be erythematous, inflamed, and desquamated. A thick discharge and a white membrane cover the vagina. The purulent discharge contains many immature epithelial and pus cells without any identifiable cause. Vaginal erythema is present, and synechiae may develop in the upper vagina, causing partial occlusion. Vaginal pH may be elevated. Wet mount and Gram's stain demonstrate an increased number of parabasal cells, an absence of gram-positive bacilli, and the presence of gram-positive cocci.
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The recommended therapy is intravaginal administration of 2% clindamycin cream 5 g daily for 7 days or clindamycin pessaries followed by a foam containing hydrocortisone and pramoxine into the vaginal mucosa to create a protective layer. A second line of therapy is vaginal insertion of corticosteroids in the form of suppository or cream. Recently, application of tacrolimus cream, as an immunosuppressor agent, has also been suggested.
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Chemical vaginitis secondary to multiple irritating offenders, including topical irritants (sanitary supplies, spermicides, feminine hygiene supplies, soaps, perfumes); allergens (latex, antimycotic creams), and possibly excessive sexual activity, can cause pruritus, irritation, burning, and vaginal discharge. The etiology may be confused with vulvovaginal candidiasis. Treatment consists of removal of the offending agent. A short course of corticosteroid treatment may be used along with sodium bicarbonate sitz baths and topical vegetable oils.
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Prepubertal, lactating, and postmenopausal women lack the vaginal effects of estrogen production. The pH of the vagina is abnormally high, and the normally acidogenic flora of the vagina may be replaced by mixed flora. The vaginal epithelium is thinned and more susceptible to infection and trauma. Although most patients are asymptomatic, many postmenopausal women report vaginal dryness, spotting, presence of a serosanguineous or watery discharge, and/or dyspareunia. Some of the symptoms of irritation are caused by a secondary infection. On examination, the vaginal mucosa is thin, with few or absent vaginal folds. The pH is 5.0–7.0. The wet mount shows small, rounded parabasal epithelial cells and an increased number of polymorphonuclear cells.
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Treatment includes intravaginal application of estrogen cream. Because approximately one-third of the vaginal estrogen is systemically absorbed, this treatment may be contraindicated in women with a history of breast or endometrial cancer. The estradiol vaginal ring, which is changed every 90 days, may provide a preferable route of administration for some women. Estradiol hemihydrate (Vagifem) 1 tablet intravaginally daily for 2 weeks and then twice a week for at least 3–6 months may be more convenient. Systemic estrogen therapy should be considered if there are no contraindications.
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Foreign bodies commonly cause vaginal discharge and infection in preadolescent girls. Paper, cotton, or other materials may be placed in the vagina and cause secondary infection. Children may require vaginoscopy using a small-caliber hysteroscope or vaginal examination under anesthesia to identify or rule out a foreign body or tumor high in the vaginal vault. The vaginal canal can be flushed in the office using a small catheter in an attempt to remove a foreign body. In adults, a forgotten menstrual tampon, a contraceptive device, or a pessary may cause a malodorous discharge. The diagnosis can usually be made by pelvic examination.
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Clinical symptoms associated with foreign bodies include abnormal malodorous vaginal discharge and intermenstrual spotting. Symptoms are generally secondary to drying of the vaginal epithelium and micro-ulcerations, which can be detected by colposcopy. Ulcerative lesions, particularly associated with tampon use, are typically located in the vaginal fornices and have rolled, irregular edges with a red granulation tissue base (Fig. 39–3). Regenerating epithelium at the ulcer edge may shed cells that may be interpreted as atypical, suggesting dysplasia. The lesions heal spontaneously once tampon use is discontinued. A foreign body retained in the vagina for a prolonged period may erode into the bladder or rectum.
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Treatment involves removal of the foreign body. Rarely, antibiotics are required for ulcerations or cellulitis of the vulva or vagina. Dryness or ulceration of the vagina secondary to use of menstrual tampons is transient and heals spontaneously.
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Toxic shock syndrome is the most serious complication associated with the use of vaginal tampons. It may develop also without tampon use. The syndrome has been linked to staphylococcal vaginal infection in healthy young women who use high-absorbency tampons continuously throughout the menstrual period. Some of the clinical manifestations are secondary to the release of staphylococcal exotoxins. Symptoms consist of a high fever (≥38.9 °C [102 °F]), possibly accompanied by severe headache, sore throat, myalgia, vomiting, and diarrhea. The disease may resemble meningitis or viremia. Palmar erythema and a diffuse sunburn-like rash have been described. The skin rash usually disappears within 24–48 hours, but occasionally a patient has a recurrent maculopapular, morbilliform eruption between days 6 and 10. Superficial desquamation of the palms and soles often follows within 2–3 weeks. Progressive hypotension may occur and proceed to shock levels within 48 hours. Multisystem organ failure may occur, including renal and cardiac dysfunction. The incidence of toxic shock syndrome was 1 in 100,000 among females 15–44 years of age in 1986. Any menstruating woman who presents with sudden onset of a febrile illness should be evaluated and treated for toxic shock syndrome. The tampon should be removed, cultures sent, and the vagina cleansed to decrease the organism inoculum. Appropriate supportive measures should be provided and β-lactamase–resistant penicillin or vancomycin (if the patient is allergic to penicillin) administered. Women who have been treated for toxic shock syndrome are at considerable risk for recurrence. Therefore, these women should avoid tampon use.
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The viruses that affect the vagina are the herpesvirus (herpes simplex, varicella-zoster, and cytomegalovirus), poxvirus (molluscum contagiosum), and papillomavirus types. The main features of these infections have been discussed under Vulvar Diseases.
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The herpesvirus (HSV) may cause erosions, ulcerations, or an exophytic necrotic mass involving the vagina or cervix and causing a profuse vaginal discharge. The cervix may be tender to manipulation and bleed easily. The primary lesion lasts approximately 2 weeks and heals without scarring. Recurrent infections may cause cervical lesions. The virus may be cultured from ulcers or ruptured vesicles. Cervical cytologic examination may reveal multinucleated giant cells with intranuclear inclusions.
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Human Papillomavirus Infection
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As discussed in the section on Vulvar Diseases, condylomata may affect the vagina and cervix as well. Condylomatous vaginitis causes a rough vaginal surface, manifesting white projections from the pink vaginal mucosa. Vaginal discharge resulting from a secondary yeast or bacterial infection is the most common symptom of florid condylomas. Postcoital bleeding may occur. No specific symptoms are related to the other types of condylomas. States of immunosuppression (pregnancy, HIV infection, diabetes, renal transplant) are associated with massive proliferation of condyloma and are often difficult to treat.
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Less common causes of vaginitis are parasitic infections with pinworms (Enterobius vermicularis) and Entamoeba histolytica. Pinworm infection is generally seen in children. Fecal contamination at the introitus is the source of infection. The perineal area is extremely pruritic. The parasite is generally detected by pressing a strip of adhesive cellulose tape to the perineum. The tape is then adhered to a slide, allowing the double-walled ova to be identified under the microscope. E histolytica infection of the vagina and cervix is rare in the United States but is quite common in developing countries. Severe infection may resemble cervical cancer, but symptoms are generally due to vulvar involvement. Trophozoites of E histolytica may be demonstrated on wet-mount preparations or occasionally on a Papanicolaou smear.
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The author thanks Dr. Doron Zarfati for assistance in obtaining some of the figures and Ms Cindy Cohen for assistance in preparing the manuscript.