What is the appropriate management for a female patient presenting with a painful vaginal lesion, potentially caused by herpes simplex virus, syphilis, or vulvar cancer?

Management of Painful Vaginal Lesions

The appropriate management begins with immediate diagnostic testing to differentiate between herpes simplex virus (HSV), syphilis, and malignancy, followed by pathogen-specific treatment—with HSV being treated with oral antivirals, syphilis with intramuscular penicillin, and suspected malignancy requiring urgent biopsy and oncologic referral. 1, 2

Initial Diagnostic Approach

The Centers for Disease Control and Prevention mandates that laboratory confirmation should always be sought because clinical diagnosis alone is often inaccurate 1. The following tests must be obtained:

• HSV culture or antigen test from the ulcer base or vesicular fluid 1
• Serologic test for syphilis (RPR or VDRL) to exclude co-infection 1
• Darkfield microscopy or direct fluorescent antibody testing for Treponema pallidum if available 2
• Testing for other STIs including Chlamydia trachomatis and Neisseria gonorrhoeae, as cervicitis can cause painful lesions 1

Critical Clinical Context

Up to 10% of patients with genital ulcers have HSV co-infected with Treponema pallidum, making concurrent testing essential 1. Even after complete diagnostic evaluation, 25% of genital ulcers have no laboratory-confirmed diagnosis 1. Non-infectious causes including Behçet syndrome, Crohn disease, and fixed drug eruption can mimic HSV 1, 2.

Physical Examination Findings to Document

Perform a comprehensive anogenital examination assessing for 3:

• Lesion characteristics: vesicles, ulcers, or masses on the vulva, labia, vagina, or surrounding genital area 1
• Lesion progression: HSV typically progresses from papules to vesicles, then bursts forming shallow ulcers that crust and heal without scarring 1
• Lymphadenopathy: inguinal or femoral lymph node involvement 3
• Cervical examination: assess for cervical friability, hyperemia, or masses that might indicate cervicitis or malignancy 4
• Vulvar inspection: look for evidence of chronic changes, pigmentation abnormalities, or masses concerning for vulvar cancer 3

Treatment Based on Etiology

Herpes Simplex Virus (First Episode)

For first-episode genital herpes, the FDA-approved treatment is 5:

• Valacyclovir 1 gram orally twice daily for 10 days, OR
• Acyclovir 200 mg orally 5 times daily for 7-10 days 3
• Alternative: Acyclovir 400 mg orally 3 times daily 3

The Centers for Disease Control and Prevention recommends initiating therapy within 72 hours of symptom onset for maximum effectiveness 5. Patients should be counseled that valacyclovir is not a cure and that asymptomatic viral shedding can occur 5.

Herpes Simplex Virus (Recurrent Episodes)

For recurrent episodes, treatment should be initiated within 24 hours of symptom onset 5:

• Valacyclovir 500 mg orally twice daily for 3-5 days 5
• Alternative: Acyclovir 200 mg orally 5 times daily for 5 days, or 400 mg 3 times daily for 5 days, or 800 mg twice daily for 5 days 3

Most immunocompetent patients with recurrent disease do not benefit significantly from treatment unless initiated during the prodrome or within 2 days of lesion onset 3.

Syphilis (Primary)

For genital ulcers caused by primary syphilis 2:

• Penicillin G benzathine 2.4 million units intramuscularly as a single dose

Suspected Vulvar or Vaginal Cancer

If malignancy is suspected based on examination findings (mass, non-healing ulcer, atypical appearance) 3:

• Immediate punch biopsy of all suspicious lesions, ensuring inclusion of underlying stroma and avoiding necrotic areas 3
• Document lesion size, location relative to midline, and relationship to adjacent organs (urethra, vagina, anus) 3
• MRI pelvis is the modality of choice for assessing locoregional disease extent if biopsy confirms malignancy 3
• Urgent gynecologic oncology referral for staging and treatment planning 3

Squamous cell carcinoma accounts for 90% of vulvar cancers and 80-90% of vaginal cancers, with 5-year survival of 86% for vulvar-confined disease but only 57% with regional lymph node metastases 3.

Common Pitfalls to Avoid

• Do not rely on clinical diagnosis alone for HSV—up to 25% of genital ulcers remain undiagnosed even after full workup, and clinical accuracy is poor 1, 2
• Do not miss co-infections—test for syphilis in all patients with genital ulcers, as 10% have concurrent HSV and syphilis 1
• Do not delay biopsy of atypical, non-healing, or mass-like lesions—HSV can rarely present as a cervical or vulvar mass mimicking cancer, but cancer must be excluded 6, 7
• Do not initiate HSV treatment beyond 72 hours for first episodes or 24 hours for recurrent episodes without counseling patients about limited effectiveness 5
• Do not overlook HIV testing in patients with lifestyle risk factors, as HIV-infected patients may have more severe or atypical presentations 3

Special Populations

In HIV-infected patients with recurrent genital herpes 5:

• Valacyclovir 500 mg orally twice daily for acute episodes
• Consider suppressive therapy if CD4+ count is adequate and recurrences are frequent
• Monitor for acyclovir-resistant strains in profoundly immunosuppressed patients 7

In cancer patients receiving cytotoxic therapy, HSV may present atypically with more severe and prolonged mucocutaneous infection or visceral disease 7. Acyclovir remains the treatment of choice, with consideration for prophylaxis in high-risk patients 7.