A woman presents with a single painful ulcerated vulvar lesion that looks like HPV; what are the likely causes and how should it be evaluated and managed?

Evaluation and Management of a Painful Ulcerated Vulvar Lesion

Most Likely Diagnosis

This presentation is most consistent with genital herpes simplex virus (HSV) infection, not HPV, as HSV accounts for approximately 49% of all genital ulcer cases and characteristically presents as painful ulcerations, whereas HPV typically causes painless wart-like lesions. 1

Critical Differential Diagnosis

The key differential diagnoses for a single painful ulcerated vulvar lesion include:

• Genital HSV (most likely): Presents with painful shallow ulcers that may be preceded by vesicles; accounts for 49% of genital ulcers 1
• Primary syphilis: Classically a painless indurated chancre, though only 31% present with classic features; can occasionally be painful 1
• Chancroid (Haemophilus ducreyi): Painful ulcers with ragged, undermined edges and purulent bases; tender inguinal adenopathy in one-third of cases 1
• Aphthous ulcers (Lipschütz ulcers): Non-venereal acute vulvar ulcers, predominantly in young virgins, with flu-like prodrome 2, 3
• Vulvar squamous cell carcinoma: Can present as a single ulcerated mass, especially in older women with chronic lichen sclerosus 2

Essential Diagnostic Workup

Immediate laboratory testing should include:

• HSV culture or PCR from the ulcer base (gold standard for HSV diagnosis) 1
• Serologic testing for syphilis (90% of primary syphilis cases show positive titers) 1
• HIV screening at presentation and repeat at 3 months if initially negative (genital ulcers facilitate HIV transmission) 1
• Dark-field microscopy or direct immunofluorescence for Treponema pallidum if available (provides immediate syphilis diagnosis) 1
• Culture for H. ducreyi if chancroid is suspected (sensitivity approximately 80%) 1

Physical Examination Findings to Document

• Ulcer morphology: Note whether borders are well-delimited, undermined, or irregular; assess for fibrinous/necrotic center versus clean base 1
• Inguinal lymphadenopathy: Painful enlarged nodes suggest HSV or syphilis; tender unilateral nodes strongly suggest chancroid 2, 1
• Presence of vesicles: Vesicular lesions progressing to shallow ulcerations that crust strongly support HSV over syphilis 1
• Bartholin gland examination: Swelling at 4 and 8 o'clock positions may indicate bacterial infection including STI pathogens 2

Empiric Treatment Strategy

Because 25% of genital ulcers remain without laboratory confirmation despite comprehensive testing, and co-infection occurs in 3-10% of cases, empiric treatment is often necessary while awaiting results. 1

First-Line Empiric Regimen:

• For presumed HSV: Acyclovir 400 mg orally five times daily for 10 days, initiated within 72 hours of symptom onset 1
  • Alternative: Valacyclovir 1 g orally twice daily for 7-10 days 1

Additional Coverage When Diagnosis Uncertain:

• Empiric syphilis coverage: Benzathine penicillin G 2.4 million units intramuscularly (single dose) 1
• Empiric chancroid coverage (if endemic or high-risk): Azithromycin 1 g orally (single dose) OR ceftriaxone 250 mg intramuscularly 1

Follow-Up and Response Monitoring

Clinical reassessment should occur 3-7 days after therapy initiation:

• Ulcers should improve subjectively within 3 days and objectively within 7 days of appropriate treatment 1
• Large or extensive ulcers may require more than 2 weeks for complete healing 1

If No Improvement by Day 3-7, Consider:

• Incorrect initial diagnosis 1
• Co-infection with another pathogen (occurs in 3-10% of cases) 1
• Underlying HIV infection 1
• Antimicrobial resistance 1
• Biopsy is indicated if lesions are pigmented, indurated, fixed, ulcerated, or not responding to therapy 2, 4

Critical Pitfalls to Avoid

• Do not rely solely on clinical appearance: Visual diagnosis is often inaccurate; laboratory confirmation is essential 1
• Do not assume single pathogen: Co-infection with two or more organisms occurs in 3-10% of cases; up to 10% of chancroid cases are co-infected with T. pallidum or HSV 1
• Do not dismiss HPV testing limitations: Negative HPV testing does not exclude HPV-related pathology, but painful ulceration is atypical for HPV 2, 4
• Do not delay HIV testing: Repeat at 3 months if initially negative to capture seroconversion 1

Special Considerations for Immunocompromised Patients

• Slower healing and higher treatment failure rates 4
• Increased risk for atypical presentations and opportunistic infections 1
• More frequent need for biopsy to exclude squamous cell carcinoma 4
• May require prolonged therapy courses beyond standard regimens 4

When to Consider Malignancy

Biopsy is mandatory if:

• Patient is older with history of chronic lichen sclerosus (5% risk of vulvar SCC) 2
• Lesion is indurated, fixed, or has irregular borders 2, 4
• No response to appropriate antimicrobial therapy 2
• Patient is immunocompromised 2, 4

Approximately 60% of vulvar squamous cell carcinomas occur on a background of lichen sclerosus, though HPV-positive tumors more commonly present as multifocal lesions rather than single ulcers 2