Is this more than just a yeast infection?

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Two lesions on the patient’s labia arouse suspicion of a second problem. An STD expert tracks down a diagnosis other clinicians might miss.

This is the third of a three-part series on sexually transmitted infections. The previous installments appeared in the May and June issues.

A 32-year-old woman presents with complaints of vaginal discharge, discomfort, and itch of two days’ duration. In the past year, she has had three yeast infections, which she self-treated, with good response. She reports no other symptoms. Her menses are regular, with the last menstrual period (LMP) two weeks before. She had a normal Pap smear at her annual visit six months ago.

When she was 20, she had chlamydia but has had no other sexually transmitted diseases (STDs). She reports five lifetime sexual partners and has been with her new partner one month. They use condoms “most of the time” for vaginal sex. Her partner is asymptomatic.

Her external genitalia are shown in Figure 1. On speculum examination, the vaginal mucosa is noted to be slightly erythematous and a white cheesy discharge is found. The cervix appears normal, without lesions or discharge. A swab test of the cervix is negative, and no friability is noted. A bimanual exam is normal, with no cervical motion tenderness. The normal-sized uterus is nontender, with no masses, and normal adnexa. There is no inguinal lymphadenopathy.

Q: Is a microscopic assessment of her vaginal discharge necessary to make a diagnosis?
Yes. Even though her exam reveals a cheesy white discharge that is the classic presentation of candidiasis, it is important to perform stat laboratory tests to make an accurate diagnosis. Trichomoniasis and bacterial vaginosis (BV) also present with vaginal discharge, and the sensitivity and specificity of symptoms plus exam findings is not adequate for diagnosis.1 Another consideration is that co-infections can occur. A complete evaluation of vaginal discharge includes pH, amine whiff test (positive in BV and often in trichomoniasis), normal saline, and KOH microscopy.

The lab results for the vaginal discharge show the following: The pH is 4.0, the amine whiff test is negative, the normal saline and KOH microscopy reveal numerous budding yeast and pseudohyphae. Few WBCs are present. No clue cells or trichomonads are seen.

Q: What is the diagnosis?
She has candidiasis. Typical symptoms of candidiasis are thick, white, curdlike discharge with vulvar pruritus, irritation, and occasionally dysuria. Vaginal discharge assessment findings of candidiasis include normal pH (<4.5) with pseudohyphae and/or budding yeast on KOH or saline wet mount. WBCs are also often found on microscopy.

Q: Is there anything on examination that makes you suspicious of another problem?
While the patient does have candidiasis, a careful inspection reveals a small crusted lesion on the left labia majora and a small shallow ulcer on the left labia minora (Figure 1). Vulvar signs of candidiasis include edema and/or erythema, fissures, excoriations and/or occasionally erythematous “satellite” papule lesions. Diffuse vaginal erosions can also occur in women with candidiasis. This patient’s findings are not typical of candidal infection and should raise concern for an unrelated etiology.

Q: What is your differential of these lesions?
It is likely that both lesions were ulcers, one of which appears partially healed. The differential for genital ulcer disease (GUD) is broad and includes STD and non-STD etiologies. Genital herpes and syphilis are more common STD etiologies of GUD in the United States; chancroid, lymphogranuloma venereum, granuloma inguinale, and acute HIV infection are less common causes. Non-STD causes include psoriasis, trauma, Reiter’s syndrome, Behçet’s syndrome, fixed drug eruption, and scabies.

Q: What laboratory testing should be done?
Direct virologic testing of the open lesion with a herpes viral culture is recommended. Herpes culture testing has variable sensitivity and is much less sensitive in healing and recurrent lesions.

A more sensitive polymerase chain reaction test can also be used, but it is a costly method of virus detection and is not FDA-approved for genital specimens.2 Since there are limitations to direct virologic testing, type-specific glycoprotein G (gG) serologic testing for HSV-2 is also recommended.3 There are several FDA-cleared gG type-specific test options: HerpesSelect-2 enzyme-linked immunosorbent assay (ELISA) Immunoglobulin G (IgG); and HerpesSelect-2 Immunoblot IgG, both from Focus Technologies; HSV-2 ELISA, from Trinity Biotech; and two point-of-care assays, Biokit HSV-2 from Biokit and SureVue HSV-2 from Fisher Scientific. These tests all have high specificity (≥96%), while the sensitivities vary from 80% to 98%, with false-negative results more likely in early primary infection.2

Older assays that aren’t able to accurately distinguish between HSV-1 and HSV-2 are not recommended, nor is the type-specific HSV-1 serologic test, because of its limited utility. Orolabial herpes caused by HSV-1 is very common; seroprevalence of HSV-1 is estimated at 58% among 14- to 49-year-olds.4 Most patients with a positive HSV-1 serology have oral infection, which can be symptomatic or asymptomatic. 2

Testing for syphilis with a nontreponemal test (RPR or VDRL) is also recommended in the evaluation of GUD. Biopsy is not part of the initial workup but is an option if the initial workup does not reveal an etiology.

Q: Should she have any other laboratory testing?
Yes. Nucleic acid amplification testing for gonorrhea and chlamydia is advised. Chlamydia and gonorrhea screening is recommended in young women (younger than 25 years) and in older women with risk factors.5,6 This patient’s history of a new partner along with her presentation of a possible new STD diagnosis indicate her risk for chlamydia and gonorrhea. HIV testing also should be offered.

Q: What treatment should she receive today, before the test results are in?
Treatment for candidiasis includes one of many intravaginal options or oral therapy with fluconazole 150 mg in a single dose (see the CDC’s STD treatment guidelines for a list of all possible regimens).2 (In this patient, the clotrimazole 100-mg vaginal tablet for seven days is prescribed.) Empiric treatment for herpes could be considered if strongly desired by the patient but is not recommended since the presentation is atypical and the symptoms are mild.

Empiric treatment for herpes would be recommended if the clinical presentation was classic for herpes with vesicles and ulcers.

Empiric treatment for syphilis is not recommended since the lesions are not classic syphilitic-appearing, and based on current epidemiology (men who have sex with men account for 60% of new syphilis cases), the woman is at low risk for syphilis.7

A few days later, the lab results arrive. The patient has a positive HSV-2 culture and positive HSV-2 serology. The chlamydia, gonorrhea, syphilis, and HIV tests are all negative.

Q: What is your diagnosis?
The positive HSV-2 culture along with a positive HSV-2 serology are evidence of recurrent herpes. The time frame for when she acquired herpes cannot be determined. Negative HSV-2 serology and a positive HSV-2 culture would be evidence of a new infection.

Q: Now that you have a diagnosis how should you counsel her about herpes?
A complete discussion regarding HSV-2 should be initiated. Information regarding HSV-2 ought to include the following: natural history of disease with possibility of future recurrent episodes; medication options (episodic therapy and suppressive therapy); transmission risks (asymptomatic shedding, abstinence during outbreaks, condom effectiveness, suppressive therapy to reduce transmission); and risk of neonatal herpes.

New research demonstrates that daily suppressive therapy can reduce transmission by nearly 50%.8 The patient should be counseled about informing current and future partners as to her HSV-2 status. Since transmission is a significant concern, the option of type-specific HSV-2 testing of her partner should be discussed. If her partner is positive, transmission of HSV-2 is not a concern. If he is negative, methods to reduce transmission, such as abstinence during outbreaks, condoms, and consideration of suppressive therapy are recommended.

This case demonstrates that herpes can present with minimal symptoms and that the diagnosis may be missed, particularly when there is coexisting vaginal infection. Clinicians may overlook small external genitalia lesions if the patient does not point them out. Manifestations of recurrent herpes in women can range from more pronounced vesicular lesions or ulcers to atypical presentations with minimal symptoms, such as vaginal pruritus or slight vaginal erythema. A history of recurrent vaginal symptoms (such as this patient’s self-diagnosed yeast infections) should raise suspicion for atypical herpes symptoms. For more information about herpes, visit the National Network of Prevention Training Centers (NNPTC) STD Case Series online(www.stdhivtraining.org). To find out about STD training, go to the NNPTC Web site (www.depts.washington.edu/nnptc).

Dr. Adler, a family physician by training, is clinical instructor at the California STD/HIV Prevention Training Center in Oakland. She wishes to credit her colleagues Heidi Bauer, MD, MS, MPH, Helene Calvet, MD, and Linda Creegan, MS, FNP, for their assistance.

References

1. Eckert LO. Clinical practice. Acute vulvovaginitis. N Engl J Med. 2006;355: 1244-1252.

2. Centers for Disease Control and Prevention. Sexually Transmitted Diseases Treatment Guidelines, 2006. MMWR. 2006;55 (No. RR-11):16-20,54-56. Available at www.cdc.gov/std/treatment/default.htm. Accessed May 24, 2007.

3. Guerry SL, Bauer HM, Klausner JD, et al. Recommendations for the selective use of herpes simplex virus type 2 serological tests. Clin Infect Dis. 2005;40:38-45.

4. Xu F, Sternberg MR, Kottiri BJ, et al. Trends in herpes simplex virus types 1 and 2 seroprevalence in the United States. JAMA. 2006;296:964-973.

5. U.S. Preventive Services Task Force. Screening for chlamydial infection: recommendations and rationale. Am J Prev Med. 2001;20(Suppl 3):90-93. Available at www.ahrq.gov/clinic/ajpmsuppl/chlarr.pdf. Accessed May 24, 2007.

6. U.S. Preventive Services Task Force. Screening for gonorrhea: recommendation statement. Ann Fam Med. 2005;3:263-267. Available at http://www.ahrq.gov/clinic/uspstf05/gonorrhea/gonrs.htm. Accessed May 24, 2007.

7. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2004. Available at: www.cdc.gov/std/stats/04pdf/2004SurveillanceAll.pdf. Accessed May 24, 2007.

8. Corey L, Wald A, Patel R, et al. Once-daily valacyclovir to reduce the risk of transmission of genital herpes. N Engl J Med. 2004;350:11-20.

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