Chronic and acute causes of vaginal discharge other than bacterial vaginosis, candidiasis, or trichomoniasis Author Jack D Sobel,

MD Section Editor Robert L Barbieri, MD Deputy Editor Vanessa A Barss, MD Disclosures Last literature review version 19.3: Fri Sep 30 00:00:00 GMT 2011 | This topic last updated: Tue Sep 27 00:00:00 GMT 2011 (More) INTRODUCTION Women may perceive a change in normal vaginal discharge, reflecting a qualitative or quantitative alteration. Clinicians should not trivialize and dismiss this complaint, instead they should evaluate the woman's symptoms by clinical examination and routine laboratory tests, such as pH and microscopy. Some of these patients have other comorbid disorders such as atopy, depression, or chronic pain syndromes, which may need to be addressed. Bacterial vaginosis, vulvovaginal candidiasis, and trichomonas vaginitis are the most common causes of vaginal discharge in premenopausal women. Recurrent or relapsing infection can be a cause of chronic vaginitis [1]. When these conditions have been excluded, other causes of vaginal discharge must be considered in the differential diagnosis of women with vaginal complaints (table 1). Causes of vaginal discharge other than the three common infections will be discussed here. The general approach to women with vaginal discharge and diagnosis and management of bacterial vaginosis, vulvovaginal candidiasis, and trichomonas vaginitis are reviewed separately. (See "Diagnostic approach to women with vaginal discharge" and "Bacterial vaginosis" and "Candida vulvovaginitis" and "Trichomonas vaginalis".) NONINFECTIOUS CAUSES The clinical features associated with noninfection related causes of vaginitis are generally indistinguishable from infection related syndromes. Symptoms such as pruritus, irritation, burning, soreness, and vaginal discharge, are most commonly confused with acute candidal vaginitis. The diagnoses discussed below should be suspected in symptomatic women in whom an infectious etiology has been excluded. Physiological leukorrhea The quantity and quality of vaginal discharge in healthy women vary both across the population and in an individual woman during her menstrual cycle (discharge is greatest at midcycle) [2]. Slight malodor and irritative symptoms can be normal [2,3]. (See "Diagnostic approach to women with vaginal discharge", section on 'Normal vaginal physiology and flora'.) Physiological leukorrhea refers to generally nonmalodorous, mucousy, white or yellowish vaginal discharge in the absence of a pathological cause. It is not accompanied by other signs and symptoms, such as pruritus, pain, burning or irritation, erythema, or friable tissue. Physiological leukorrhea is usually due to estrogen induced changes in cervicovaginal secretions. Although the reason for the increased or altered discharge is not always known, patients can be reassured that this is unlikely to be a pathologic finding in the setting of a normal vaginal and cervical examination, normal vaginal pH (less than 4.5), normal findings on microscopy, and negative amine test. Treatment is unnecessary. If there is doubt about the physiological basis for the discharge, a yeast culture and testing for chlamydia and gonorrhea should be performed. These entities, which can cause vaginal discharge, may not be identified by office examination. (See "Candida vulvovaginitis" and "Genital Chlamydia trachomatis infections in women" and "Diagnosis of gonococcal infections".) Vaginal atrophy and atrophic vaginitis Vaginal atrophy due to estrogen deficiency is common and usually asymptomatic, except for dryness. Low estrogen levels reduce vaginal secretions, which results in vaginal dryness. Occasionally, atrophic vaginitis also occurs due to superficial inflammation. The associated vaginal discharge is often watery and unpleasant. Atrophic vaginitis typically occurs in menopausal women, but can occur in women of any age who have a relative decrease in estrogenic stimulation to this area of the genitalia. In premenopausal women, hypoestrogenic settings include the postpartum period, lactation, and during administration of antiestrogenic drugs.

Atrophic vaginitis typically responds to topical estrogen therapy, which restores the vaginal epithelium; antibiotics are not needed. The pathogenesis, clinical manifestations, diagnosis, and treatment of atrophic vaginitis are discussed in detail separately. (See "Clinical manifestations and diagnosis of vaginal atrophy" and "Treatment of vaginal atrophy".) Irritants and allergens Noninfectious causes of vaginitis include irritants (eg, scented panty liners, spermicides, povidoneiodine, soaps and perfumes, and some topical drugs) and allergens (eg, latex condoms, topical antifungal agents, seminal fluid, chemical preservatives) that produce immunologic acute and chronic hypersensitivity reactions, including contact dermatitis. Management involves identifying and eliminating the offending agent and drug therapy, as indicated. However, irritants and allergens can be difficult to identify. Suggestions for good vulvovaginal hygiene are listed in the table (table 2). (See "Overview of dermatitis", section on 'Allergic contact dermatitis' and "Overview of dermatitis", section on 'Irritant contact dermatitis'.)

Healthy vulval hygiene practices Avoid Pantyhose Synthetic underwear Jeans and other tight pants Swimsuits, leotards, thongs, lycra garments Pantyliners Scented soaps or shampoos Bubble bath Scented detergents Washcloths Feminine sprays, douches, powders Dyed toilet articles Hair dryers to dry vulva skin without contact

Substitute Stockings with a garter belt Thigh high or knee high stockings Cotton underwear or no underwear Loose pants, skirts, dresses Loose-fitting cotton garments Tampons or cotton pads Fragrance free pH neutral soap (eg, Basis, Neutrogena, Dove soap) Tub baths in the morning and at night without additives and at a comfortable temperature Unscented detergents Use fingertips for washing; pat dry, don't rub dry These are not necessary products and can be omitted from personal practices Toilet articles without dyes Dry vulva by gentle patting

Desquamative inflammatory vaginitis Desquamative inflammatory vaginitis is a rare chronic clinical syndrome of unknown etiology. Some investigators believe the disorder is due to altered vaginal flora and have termed it aerobic vaginitis [ 4-6], while others believe it is a sterile inflammatory vaginitis [7]. Clinical features Desquamative inflammatory vaginitis is characterized by pain (dyspareunia, vaginal/introital pain) with diffuse exudative vaginitis and epithelial cell exfoliation, resulting in profuse vaginal discharge. On vaginal examination, a spotty ecchymotic rash is often present, or there may be diffuse or focal erythema or linear erosions. The vestibule is often affected, as well, and may be thinned and sensitive. In a large series of 98 patients diagnosed with desquamative inflammatory vaginitis (mean age 49.6 years), 70 to 90 percent had purulent vaginal discharge, dyspareunia, and vaginal inflammation [8]. No consistent microbiologic pathogen was identified except for the near absence of lactobacilli in almost all women. Diagnosis The diagnosis is based on the presence of all of the following criteria [8]: At least one of the following symptoms: vaginal discharge, dyspareunia, pruritus, burning, irritation Vaginal inflammation (spotted ecchymotic rash, erythema, focal or linear erosion) Vaginal pH >4.5 Saline microscopy showing increased parabasal and inflammatory cells (ie, leukocyte to epithelial cell ratio greater than 1:1)

Bacterial vaginosis and N. gonorrhoeae, C. trachomatis, and T. vaginalis infection should also be excluded. Negative microscopy is not sufficient to rule out trichomoniasis; culture, antigen, or DNA diagnostic tests should be performed. (See "Trichomonas vaginalis".)

Differential diagnosis In hypoestrogenemic women, severe atrophic vaginitis can mimic desquamative inflammatory vaginitis. Improvement in symptoms with estrogen therapy helps to distinguish atrophic vaginitis from desquamative inflammatory vaginitis. (See "Clinical manifestations and diagnosis of vaginal atrophy".) Other disorders in differential diagnosis include erosive lichen planus, pemphigus vulgaris, benign mucous membrane pemphigoid, and linear immunoglobulin A disease [9]. Patients with these disorders may have evidence of extragenital disease; therefore, a complete history and physical examination should be performed. Biopsy for histopathological examination and immunofluorescence studies can help to confirm these diagnoses. (See "Vulvar lichen planus", section on 'Erosive lichen planus' and "Pemphigus" and "Bullous pemphigoid and other pemphigoid disorders" and "Drug eruptions".) Treatment No randomized trials of treatment approaches have been reported. The two most common treatments are intravaginal clindamycin or glucocorticoids [8-11]. Options for initial therapy include either of the following: 2% clindamycin cream 4 to 5 grams intravaginally once daily, or 10% hydrocortisone cream 3 to 5 grams intravaginally once daily

For mild disease, hydrocortisone one-half or one 25 mg rectal suppository placed in the vagina twice daily is another option [11]. Treatment is prescribed for four weeks, and leads to dramatic improvement in symptoms in most patients. If the patient has improved after four weeks, treatment is continued until complete remission is achieved, defined as complete absence of symptoms and abnormal signs plus no increase in leukocytes or parabasal cells on saline microscopy; this may take another two weeks or longer. Upon complete remission, therapy is discontinued and the patient is followed monthly. If there has been no or poor improvement after the initial four weeks of therapy, other diagnoses in the differential diagnosis should be considered; if these diagnoses are excluded, we switch to a different therapy, eg, from clindamycin to hydrocortisone or vice versa, for a fourto six-week course. Patients who relapse after discontinuation of therapy are treated with the drug that was not used for their initial treatment (clindamycin instead of hydrocortisone or vice versa). This drug is continued until complete remission is again achieved, and then tapered gradually. In difficult to treat cases, judicious use of intravaginal tacrolimus or clobetasol may be useful [11]. Outcome Recurrence is common after discontinuation of therapy. In one study, only one fourth of patients remained cured at one year after a single course of therapy and one-third of patients relapsed within six weeks of discontinuing initial treatment [8]. Cytolytic vaginosis Cytolytic vaginosis refers to a syndrome of vaginal hyperacidity due to overgrowth by lactobacilli, although the existence of this entity is controversial. It is characterized by pruritus, dyspareunia, vulvar dysuria, and cyclical increase in symptoms during the luteal phase [12,13]. Diagnostic criteria include presence of white vaginal discharge; pH between 3.5 and 4.5; Gram's stain showing overgrowth of lactobacilli, paucity of white blood cells, evidence of cytolysis (bare nuclei, shreds of cytoplasm); and exclusion of candidal infection. Sodium bicarbonate douches have been used for treatment. A solution of one rounded teaspoon of sodium bicarbonate in 600 mL of water is used for irrigating the vagina, once per day for 7 to 14 days. Cervical and vaginal lesions Cervical and vaginal lesions can also be associated with persistent vaginal discharge. Examples include ectropion, polyps, granulation tissue, and neoplasia. These disorders can be detected by speculum examination. Treatment depends on the specific disorder, but generally consists of ablation or excision. (See "Congenital cervical anomalies and benign cervical lesions" and "Invasive cervical cancer: Epidemiology, risk factors, clinical manifestations, and diagnosis".) Fistula Vesicovaginal and rectovaginal fistulas can cause chronic vaginal discharge. The presence of a fistula should be excluded in at-risk patients (eg, postpartum, posthysterectomy, history of inflammatory bowel disease or radiation therapy). (See "Rectovaginal, anovaginal, and colovesical fistulas" and "Vesicovaginal, urethrovaginal, and ureterovaginal fistulas".) Vestibulodynia All women with vestibulodynia have introital pain with attempted intercourse; this constitutes the major feature of the syndrome. Vaginal discharge occurs in many affected women, but is not a diagnostic criterion. (See "Clinical manifestations and diagnosis of localized, provoked vulvodynia (formerly vulvar vestibulitis)".) Seminal plasma allergy Seminal plasma allergy or hypersensitivity is a rare disorder characterized by postcoital vulvovaginal itching, burning, edema, and erythema with or without systemic signs and symptoms [14,15]. Systemic reactions are

experienced as dyspnea, dysphagia, rhinoconjunctival complaints, generalized urticaria, angioedema, gastrointestinal symptoms, exacerbation of existing atopic eczema or anaphylactic shock. Most affected women are younger than 40 years and have a family history of atopy. Complaints occur immediately or within one hour after contact with seminal plasma. Human seminal plasma hypersensitivity may also present as vulvar vestibulitis syndrome or burning semen syndrome. This diagnosis can be considered after other much more common causes of vaginal symptoms have been excluded. The diagnosis is made by absence of symptoms with condom use and by positive skin testing with a pooled sample of seminal fluid. Treatment options include use of condoms or intravaginal cromolyn (4 percent cream 30 minutes prior to sexual relations) [16]. Parenteral or vaginal desensitization by immunotherapy is also possible, but requires regular (two to three times per week) intercourse to maintain the tolerant state [17]. INFECTIOUS CAUSES There are few proven infectious causes of vaginitis other than Candida vaginitis, trichomoniasis, bacterial vaginosis and rare Group A streptococcal vaginitis. Each entity requires diagnostic confirmation including microscopy and newer laboratory tests. Culture is of limited value; it is useful only for Candida species and Group A streptococci. Identification of other bacterial species on culture or PCR is of no value and is misleading since a variety of bacterial species may colonize the vagina and are not vaginal pathogens. (See "Diagnostic approach to women with vaginal discharge" and "Bacterial vaginosis" and "Candida vulvovaginitis" and "Trichomonas vaginalis".) Non-specific bacterial vaginitis The concept of non-specific bacterial vaginitis is no longer acceptable. In the past, many women with bacterial vaginosis were given the diagnosis of non-specific vaginitis, but this should no longer occur since clear diagnostic criteria for bacterial vaginosis are now available. (See "Bacterial vaginosis", section on 'Diagnosis'.). Vaginal bacterial cultures are rarely indicated in women with vaginal discharge. In fact, they are frequently misleading and therefore lead to unnecessary antibacterial therapy. Apart from Group A streptococcus, a clear causal relationship between bacteria and vaginitis has not been established. We recommend obtaining a culture for Group A streptococcus only in women with inflammatory vulvovaginitis, purulent discharge, polymorphonuclear leukocytes on wet mount, and elevated vaginal pH (see 'Streptococcal vulvovaginitis' below). Treatment of infectious causes of vulvovaginitis should be targeted to the causative organism. Sulfanilamide cream (eg, triple sulfa or AVC cream) has no role in the treatment of vulvovaginitis, as it is less effective than other therapies (eg, metronidazole for trichomonas vaginalis and bacterial vaginosis, fluconazole for candida vulvovaginitis) [18,19]. Foreign bodies A foreign body (eg, retained tampon) can be associated with chronic vaginal discharge, intermittent bleeding or spotting, and/or a foul smelling odor due to inflammation and infection. Removal of the foreign body is generally adequate treatment. Antibiotics are rarely indicated. Staphlococcal toxic shock syndrome has been associated with tampon use. It is a multiorgan systemic disease; vaginal findings include hyperemia of the vaginal mucosa and, in more severe cases, superficial ulcerations occur on the mucous membranes, and petechiae, vesicles, and bullae develop. (See "Staphylococcal toxic shock syndrome".) Cervicitis Cervicitis can present with vaginal discharge that may be confused with vaginitis. Neisseria gonorrhoeae and Chlamydia trachomatis are the two most common causes, followed by herpes simplex virus and mycoplasma genitalum. Cervicitis related to cytomegalovirus has been described, but is usually asymptomatic [20]. None of these organisms cause vaginitis. The clinical manifestations, diagnosis, and treatment of cervicitis are discussed in detail separately. (See "Acute cervicitis".) Streptococcal vulvovaginitis Group A streptococcus Group A streptococcus (Streptococcus pyogenes [GAS]) is an uncommon cause of vulvovaginitis [21,22]. In one series of almost 7000 pregnant women, only 0.03 percent were colonized with GAS [21]. GAS vulvovaginitis typically occurs in prepubertal girls and in mothers whose children suffer from active GAS infection or who serve as GAS carriers. Carriage or exposure to a carrier is an important source of recurrent GAS infection. GAS can colonize and be transmitted from skin (especially in individuals with chronic dermatological conditions), nasopharynx, and the gastrointestinal tract (including the perianal area) [23]. Clinical features include acute onset of frankly purulent discharge accompanied by pruritus, soreness and irritation, erythema, labial edema, and possibly dysuria from burning of the skin with voiding. Microscopy of the discharge reveals a marked increase in polymorphonuclear leukocytes and Gram's stain shows chains of gram-positive cocci. Penicillin treatment after confirmation of the diagnosis by culture rapidly leads to cure. We use Penicillin VK 500 mg four times daily for 10 to 14 days or clindamycin cream 2 percent per vaginam for 7 to 10 days.

Group B streptococcus Group B streptococcus (GBS) commonly colonizes the vagina: approximately 20 percent of women are colonized with GBS [21,24]. Whether GBS is a pathogen in vulvovaginitis is controversial. Some clinicians believe it has a pathogenic role in vulvovaginitis and report an ameliorative effect on vulvovaginal symptoms with antibiotic treatment (oral penicillin or clindamycin cream). We and most experts do not believe this organism has a pathogenic role in symptomatic vulvovaginitis and that positive culture results merely reflect colonization, which is facilitated by disruption of the normal vaginal bacterial environment [24]. Therefore, in women with vaginitis both GBS culture and treatment of positive culture results should be avoided. S. pneumonia This organism does not cause vaginitis. Condyloma acuminata Clinical manifestations of vaginal warts include vaginal discharge, pruritus, bleeding, burning, tenderness, and pain. Diagnosis and treatment are discussed separately. (See "Condylomata acuminata (anogenital warts)" and "Treatment of vulvar and vaginal warts".) Recurrent or relapsing infection Recurrent or relapsing vulvovaginal candidiasis and bacterial vaginosis account for a significant proportion of cases of chronic vaginitis [1]. These entities should be excluded by clinical examination and candidal culture. (See "Candida vulvovaginitis", section on 'Recurrent vulvovaginal candidiasis' and "Bacterial vaginosis", section on 'Relapse and recurrent infection'.) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, The Basics and Beyond the Basics. The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on patient info and the keyword(s) of interest.) Beyond the Basics topics (see "Patient information: Vaginal discharge in adults" and "Patient information: Chlamydia" and "Patient information: Gonorrhea")

SUMMARY AND RECOMMENDATIONS Women with vaginal discharge should undergo clinical examination of the lower genital tract and laboratory tests, such as vaginal pH and microscopy of vaginal discharge. Results of this evaluation help to determine the etiology of the vaginitis. The clinical features associated with noninfectious causes of vaginitis are generally indistinguishable from infection related syndromes. (See 'Introduction' above.) Physiological leukorrhea is usually due to estrogen induced changes in cervicovaginal secretions. Vaginal and cervical examination, vaginal pH, and findings on microscopy are all normal. Treatment is unnecessary. (See 'Physiological leukorrhea' above.) Vaginal discharge and symptoms of vulvovaginal discomfort can be caused by irritants (eg, scented panty liners, pads, spermicides, povidone-iodine, soaps and perfumes, and some topical drugs) and allergens (eg, latex condoms, topical antifungal agents, seminal fluid, chemical preservatives) that produce immunologic acute and chronic hypersensitivity reactions, including contact dermatitis. Identifying and eliminating the offending agent is generally adequate treatment. (See 'Irritants and allergens' above.) Desquamative inflammatory vaginitis is a rare cause of chronic vaginal discharge. It is characterized by purulent vaginal discharge, vulvovaginal burning or irritation, dyspareunia, and vulvar and vaginal erythema. The diagnosis is based on the presence of purulent vaginal discharge, leukocyte to epithelial cell ratio greater than 1:1, and vaginal pH greater than 4.5, after excluding bacterial vaginosis, N. gonorrhoeae, C. trachomatis, and T. vaginalis infection. We suggest 2% clindamycin or 10% hydrocortisone cream intravaginally at bedtime for four weeks (Grade 2C). (See 'Desquamative inflammatory vaginitis' above.) Structural cervical or vaginal lesions, such as warts, polyps, granulation tissue, ectropion, fistulas, and neoplasia, and foreign bodies can cause vaginal discharge. These lesions can be seen on speculum examination. Treatment is by ablation or excision, or removal of the foreign body. (See 'Cervical and vaginal lesions' above and 'Fistula' above and 'Condyloma acuminata' above and 'Foreign bodies' above.) Vestibulodynia should be considered if pain is a prominent symptom. (See 'Vestibulodynia' above.) Cervicitis can present with vaginal discharge that may be confused with vaginitis. Neisseria gonorrhoeae and Chlamydia trachomatis are the two most common causes, followed by herpes simplex virus. (See 'Cervicitis' above.)

Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. Nyirjesy P, Peyton C, Weitz MV, et al. Causes of chronic vaginitis: analysis of a prospective database of affected women. Obstet Gynecol 2006; 108:1185. Anderson M, Karasz A, Friedland S. Are vaginal symptoms ever normal? a review of the literature. MedGenMed 2004; 6:49. Anderson MR, Klink K, Cohrssen A. Evaluation of vaginal complaints. JAMA 2004; 291:1368. Donders GG. Definition and classification of abnormal vaginal flora. Best Pract Res Clin Obstet Gynaecol 2007; 21:355. Donders GG, Vereecken A, Bosmans E, et al. Definition of a type of abnormal vaginal flora that is distinct from bacterial vaginosis: aerobic vaginitis. BJOG 2002; 109:34. Donders G, Bellen G, Rezeberga D. Aerobic vaginitis in pregnancy. BJOG 2011; 118:1163. Murphy R. Desquamative inflammatory vaginitis. Dermatol Ther 2004; 17:47. Sobel JD, Reichman O, Misra D, Yoo W. Prognosis and treatment of desquamative inflammatory vaginitis. Obstet Gynecol 2011; 117:850. Sobel JD. Desquamative inflammatory vaginitis: a new subgroup of purulent vaginitis responsive to topical 2% clindamycin therapy. Am J Obstet Gynecol 1994; 171:1215. Murphy R, Edwards L. Desquamative inflammatory vaginitis: what is it? J Reprod Med 2008; 53:124. Jensen JT. An outline: Prognosis and treatment of DIV. Contraceptive Technology Update 2011; 32:S3. Cibley LJ, Cibley LJ. Cytolytic vaginosis. Am J Obstet Gynecol 1991; 165:1245. Cerikcioglu N, Beksac MS. Cytolytic vaginosis: misdiagnosed as candidal vaginitis. Infect Dis Obstet Gynecol 2004; 12:13. Bernstein IL, Englander BE, Gallagher JS, et al. Localized and systemic hypersensitivity reactions to human seminal fluid. Ann Intern Med 1981; 94:459. Weidinger S, Ring J, Khn FM. IgE-mediated allergy against human seminal plasma. Chem Immunol Allergy 2005; 88:128. Bosso JV, Aiken MJ, Simon RA. Successful prevention of local and cutaneous hypersensitivity reactions to seminal fluid with intravaginal cromolyn. Allergy Proc 1991; 12:113. Ohman JL Jr, Malkiel S, Lewis S, Lorusso JR. Allergy to human seminal fluid: characterization of the allergen and experience with immunotherapy. J Allergy Clin Immunol 1990; 85:103. Rein MF. Current therapy of vulvovaginitis. Sex Transm Dis 1981; 8:316. duBouchet L, Spence MR, Rein MF, et al. Multicenter comparison of clotrimazole vaginal tablets, oral metronidazole, and vaginal suppositories containing sulfanilamide, aminacrine hydrochloride, and allantoin in the treatment of symptomatic trichomoniasis. Sex Transm Dis 1997; 24:156. McGalie CE, McBride HA, McCluggage WG. Cytomegalovirus infection of the cervix: morphological observations in five cases of a possibly under-recognised condition. J Clin Pathol 2004; 57:691. Mead PB, Winn WC. Vaginal-rectal colonization with group A streptococci in late pregnancy. Infect Dis Obstet Gynecol 2000; 8:217. Bray S, Morgan J. Two cases of group A streptococcal vulvovaginitis in premenopausal adults in a sexual health setting. Sex Health 2006; 3:187. Sobel JD, Funaro D, Kaplan EL. Recurrent group A streptococcal vulvovaginitis in adult women: family epidemiology. Clin Infect Dis 2007; 44:e43. Leclair CM, Hart AE, Goetsch MF, et al. Group B streptococcus: prevalence in a non-obstetric population. J Low Genit Tract Dis 2010; 14:162.

20. 21. 22. 23. 24.