Vaginal Candidiasis

Etiology

Candidal vulvovaginitis is caused by inflammatory changes in the vaginal and vulvar epithelium secondary to infection with Candida species, most commonly Candida albicans. However, Candida is part of the normal flora in many women, identified in 10% of asymptomatic women.[2] Therefore, candidal vulvovaginitis requires both the presence of Candida in the vagina and associated symptoms (eg, irritation, itching, dysuria, or inflammation).[3]

Epidemiology

Candidal vulvovaginitis is a common condition responsible for a third of all cases of vulvovaginitis in reproductive-aged women. Approximately 70% of women report having had candidal vulvovaginitis in their lifetime, and an estimated 8% of women suffer recurrent candidal vulvovaginitis.[4] The most common responsible pathogen is C. albicans, accounting for 90% of cases, with most of the remaining cases caused by Candida glabrata. Because over-the-counter treatments are widely available, candidal vulvovaginitis is under-reported; therefore, detailed epidemiological data for this disease process is unavailable.[5] Furthermore, diagnosis is based on both clinical and ancillary evaluation. As a result, epidemiologic reports based on culture alone, in which 10% of asymptomatic women have positive candidal cultures, overestimate the disease incidence. Furthermore, studies demonstrate that because self-diagnosis is inaccurate, data derived from a patient query is also imprecise.[6]

Recognized risk factors for acute candidal vulvovaginitis include estrogen use, elevated endogenous estrogens (eg, pregnancy or obesity), diabetes mellitus, immunosuppression (ie, chemotherapy or antimetabolite medications, HIV infection, or transplant patients), and broad-spectrum antibiotic use. Although candidal vulvovaginitis is more common in sexually active women, evidence that candidal infection is sexually transmitted is lacking. Patients with recurrent candidal vulvovaginitis, defined as 4 or more episodes of culture-proven candidal vulvovaginitis, have predisposing genetic factors that cause them to be susceptible to recurrent fungal infections. These factors may also cause a predisposition to Candida hypersensitivity reactions.[7]

Pathophysiology

Candidal vulvovaginitis occurs when Candida species superficially penetrate the mucosal lining of the vagina and cause an inflammatory response. The dominant inflammatory cells are typically polymorphonuclear cells and macrophages. The inflammatory response results in copious thick discharge and vaginal irritation, excoriations, dysuria, itching, burning, dyspareunia, or swelling.[8]

History and Physical

Characteristic clinical symptoms of vaginal candidiasis include vaginal and vulvar irritation, itching, and burning. Symptoms are often prominent just before the patient's menstrual period. Many patients have a history of similar symptoms and report attempting over-the-counter treatment with topical agents or alternative therapies.

On pelvic exam, common findings include vulvar and vaginal erythema, excoriations, thick white adherent discharge, and swelling. In some patients, little to no discharge is noted. In patients with candidal vulvovaginitis, inflammation is evident during a pelvic exam. However, the cervix is typically normal and not inflamed. The patient should not have cervical motion tenderness, and there should be no abnormal discharge from the cervical os. Ulcers, asymmetric swelling or masses, or foreign bodies should prompt consideration of differential diagnoses. The degree of irritation is typically severe in patients with acute vulvovaginal candidiasis. Conversely, patients with Candida glabrata infections usually have mild symptoms. Various vulvovaginitis etiologies have similar presentations, and therefore, further diagnostic studies, including wet mount, whiff testing, and pH testing, should be considered for uncertain diagnoses.[9]

Evaluation

Diagnostic studies utilized to confirm the presence of Candida include 10% potassium hydroxide (KOH) and wet mount smears of the vaginal discharge for microscopy, pH testing, and potentially fungal culture or commercial polymerase chain reaction (PCR) tests. In patients with vulvovaginal candidiasis, the vaginal pH is typically below 5.[ACOG Practice bulletin 215 Vaginitis in Nonpregnant] Characteristic findings of vaginal candidiasis include the prominence of lactobacillus bacteria and inflammatory cells on wet prep, a negative Whiff test (ie, no fishy odor with the application of KOH to the slide), and budding yeast, hyphae, or pseudohyphae on microscopy, which are typically seen most easily on the KOH prep.[10] Microscopy and pH testing can also identify clue cells, indicating bacterial vaginosis, and trichomonads, indicating trichomoniasis, which should be ruled out (or diagnosed) concurrently.[11]

Most infections are secondary to Candida albicans; therefore, consistent microscopy findings in the clinical setting of a reproductive-age woman with vulvovaginitis, confirmatory cultures for Candida are unnecessary. Cultures should be considered in patients with recurrent disease and patients with a negative work-up in the setting of symptoms consistent with vulvovaginal candidiasis.[12] (Ref: ACOG PB 215). However, if cultures cannot be performed, empiric treatment is reasonable.[13] 

Because Candida species are part of normal vaginal flora in many women, routine cultures in asymptomatic women are discouraged. 

Treatment / Management

Acute candidal vulvovaginitis is treated with antifungal agents. Since most candidal vulvovaginitis cases are secondary to C albicans species, and C albicans does not demonstrate resistance to azole antifungals, these are the agents of choice.[14] Antifungals may be administered through several methods, including a single dose of fluconazole 150 mg orally or terconazole applied intravaginally once or in multiple dose regimens ranging from 3 to 7 days available over the counter. These options are equally efficacious in patients with uncomplicated disease (eg, immunocompetent status or nonrecurrent candidal vulvovaginitis). Therefore, treatment decisions may be based on cost, patient preference, and drug interactions. In unresponsive patients, cultures may be warranted to look for other Candida species, often resistant to standard therapy.[15](B3)

For complicated candidal vulvovaginitis, including patients who are immunosuppressed or have a recurrent infection, extended treatment regimens are commonly utilized, such as intravaginal azole therapy for at least 1 week or oral treatment with fluconazole 150 mg (renally adjusted for CrCl <50 ml/min) once every 3 days for 3 doses. Patients with recurrent candidal vulvovaginitis may benefit from suppressive therapy with weekly oral fluconazole for 6 months. However, pregnant patients should not be given oral antifungals. In these patients, a 7-day course of intravaginal treatment is recommended. Fluconazole is considered safe in breastfeeding women.[16] Nonpharmacologic therapies (eg, intravaginal or oral yogurt therapy, intravaginal garlic, or douching) have not been found to be effective.

Differential Diagnosis

Differential diagnoses that should also be considered include:

• Allergic reaction
• Atopic dermatitis
• Lichen sclerosis
• Lichen simplex chronicus
• Neoplasm
• Paget disease
• Physiologic leukorrhea
• Psoriasis
• Sexual abuse
• Vulvodynia

Prognosis

Despite appropriate treatment, recurrence is relatively common and is estimated to range from 14% to 28% in otherwise healthy individuals.[17] Most often, recurrent disease arises from persistent vaginal organisms or endogenous reinfection with an identical strain of Candida. Less commonly, the disease may result from a new strain of Candida. Recurrent disease may be triggered by antibiotic use, sexual activity, or dietary factors. Genetic susceptibility may also affect a person's risk for recurrent disease.

Topical imidazole and oral fluconazole are less likely to be effective in patients with non-albicans species of Candida. Therefore, fungal culture is indicated in patients with persistent symptoms after standard treatment for uncomplicated vulvovaginal candidiasis. Boric acid (600 mg vaginally for at least 14 days) is often effective against C glabrata and other atypical species. Note that boric acid can be fatal if orally ingested, so patients must be well-counseled on its use.[18]

Complications

Complications secondary to vaginal candidiasis are rare but, in severe cases, may cause extensive vulvar erythema, edema, excoriation, and vaginal or vulvar fissures.[13] Adverse events that may occur with antifungal treatment include abdominal pain, nausea and vomiting, diarrhea, flatulence, headache, central nervous system disorder, musculoskeletal disorder, rash, allergic reaction, menstrual disorder, and alopecia.[19]