How should I evaluate and manage a woman with a single ulcerated vulvar lesion that is intermittently painful?

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Evaluation and Management of a Single Ulcerated Vulvar Lesion with Intermittent Pain

Begin with immediate diagnostic testing for herpes simplex virus (HSV) via PCR or culture from the ulcer base, as HSV accounts for approximately 49% of all genital ulcers and is the most common cause in women presenting with painful vulvar lesions. 1

Initial Diagnostic Workup

The following tests must be performed on all patients with genital ulcers, regardless of clinical appearance:

  • HSV PCR or culture from the ulcer base – This is the gold standard and should be the first test ordered, as genital herpes is the leading cause of ulcerative genital lesions 1, 2
  • Serologic testing for syphilis (RPR or VDRL) – Mandatory in all cases, though sensitivity is only 62-78% in primary syphilis 3
  • Darkfield microscopy or direct immunofluorescence for Treponema pallidum if available – Provides immediate diagnosis of primary syphilis 1, 3
  • HIV testing at initial presentation – Genital ulcers facilitate HIV transmission and must be screened; repeat at 3 months if initially negative 1, 2
  • Culture for Haemophilus ducreyi if chancroid is endemic in your region (sensitivity ~80%) 1

Critical Diagnostic Pitfalls to Avoid

Do not rely on clinical appearance alone – diagnosis based solely on history and physical examination is often inaccurate, with at least 25% of genital ulcers remaining undiagnosed even after comprehensive testing. 1, 3

Key considerations:

  • Co-infection occurs in 3-10% of cases – A single positive test does not exclude other pathogens; up to 10% of patients have HSV co-infected with T. pallidum 1, 2, 3
  • Pain does not reliably distinguish etiologies – While HSV typically causes painful ulcers, the classic painless syphilitic chancre occurs in only 31% of primary syphilis cases 3
  • Intermittent pain suggests HSV – The characteristic progression from vesicles to shallow ulcerations that crust and heal spontaneously strongly supports HSV over syphilis 1

Physical Examination Findings to Document

  • Ulcer morphology: Note whether borders are well-delimited, undermined, or have a clean base versus fibrinous/necrotic center 1
  • Inguinal lymphadenopathy: Painful enlarged nodes suggest HSV or syphilis; tender unilateral nodes strongly suggest chancroid 1
  • Bartholin gland examination: Check for swelling at 4- and 8-o'clock positions indicating possible bacterial infection 1

Treatment Algorithm

If HSV is Confirmed or Highly Suspected:

Initiate acyclovir 400 mg orally five times daily for 10 days within 72 hours of symptom onset for maximal efficacy. 1

Alternative regimens include:

  • Acyclovir 200 mg orally five times daily for 7-10 days 1
  • Valacyclovir 1 g orally twice daily for 7-10 days 1

If Diagnosis is Unclear or Test Results Pending:

Many experts recommend empiric coverage for both syphilis and chancroid when the diagnosis is uncertain, particularly in communities with notable chancroid prevalence or when diagnostic capabilities are limited. 4, 1

Empiric regimen:

  • For syphilis: Benzathine penicillin G 2.4 million units IM as a single dose 1
  • For chancroid: Azithromycin 1 g orally as a single dose OR ceftriaxone 250 mg IM as a single dose 4, 1

Follow-Up and Monitoring

Re-examine the patient 3-7 days after initiating therapy. 4, 1

Expected response:

  • Ulcers should improve symptomatically within 3 days 4, 1
  • Objective improvement should be evident within 7 days 4, 1
  • Large ulcers may require more than 2 weeks for complete healing 1

If No Clinical Improvement by Day 3-7, Consider:

  • Incorrect initial diagnosis 4, 1
  • Co-infection with another sexually transmitted pathogen 4, 1
  • Underlying HIV infection (requires modified treatment approach) 4, 1
  • Antimicrobial resistance 4, 1
  • Non-infectious etiologies: Behçet syndrome, Crohn disease, fixed drug eruption, or sexual trauma 2, 5

Special Considerations for HIV-Infected Patients

HIV-positive women may experience slower healing, higher treatment failure rates, and require prolonged therapy courses beyond standard regimens. 4

  • Consider the 7-day erythromycin regimen (500 mg orally four times daily) if HIV infection is known and follow-up can be assured 4
  • Close monitoring is essential as treatment failures occur more frequently, especially with shorter-course regimens 4

Repeat Testing Protocol

If initial HIV and syphilis serologies are negative, repeat testing at 3 months is mandatory to capture seroconversion. 4, 1

Patient Counseling Points

  • Emphasize that up to 25% of genital ulcers remain undiagnosed despite thorough testing, highlighting the importance of follow-up and possible empiric therapy 1
  • Advise complete avoidance of sexual activity until ulcers heal to prevent trauma and potential transmission 2
  • For non-infectious ulcers (if ultimately diagnosed), explain that aphthous-spectrum lesions can occur without sexual transmission, particularly after viral illnesses 2
  • Recommend gentle hygiene with mild, unscented cleansers and avoidance of potential irritants 2

References

Guideline

Diagnosis and Management of Genital Ulcer Disease – Evidence‑Based Summary

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Guideline

Management of Vaginal Labial Ulcers

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Diagnostic Approach for Painless Genital Ulcer

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Diagnosis and management of genital ulcers.

American family physician, 2012

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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