What is the diagnosis and treatment for a sexually active female of reproductive age presenting with white ulcerated nodules on the labia minora, surrounding erythema, and pain?

White Ulcerated Nodules on Labia Minora with Pain and Erythema

In a sexually active woman of reproductive age presenting with painful white ulcerated nodules on the labia minora with surrounding erythema, the most likely diagnosis is genital herpes simplex virus (HSV) infection, and empiric treatment with oral acyclovir, valacyclovir, or famciclovir should be initiated immediately while awaiting confirmatory testing. 1, 2, 3

Diagnostic Approach

The clinical presentation of white ulcerated nodules with pain and erythema strongly suggests HSV infection, which is the most common cause of genital ulcers in the United States. 1, 2, 3, 4

Essential diagnostic testing includes:

• HSV culture or PCR from the ulcer base or vesicular fluid - this is the gold standard for confirming HSV infection 1, 2
• Serologic testing for syphilis - mandatory in all patients with genital ulcers, as syphilis is the second most common cause and up to 10% of patients have HSV co-infected with Treponema pallidum 1, 2
• Darkfield microscopy or direct fluorescent antibody testing for T. pallidum if available 1, 3
• HIV testing - strongly recommended given the association between genital ulcers and increased HIV transmission risk 1, 2
• Culture for Haemophilus ducreyi only if practicing in areas with high chancroid prevalence 1, 2

Distinguishing Clinical Features

HSV infection characteristics:

• Painful vesicles that rupture forming shallow ulcers or erosions 1
• Episodes typically last less than 10 days 1
• May have prodromal symptoms (tingling, burning) 3
• Surrounding erythema is common 1

Critical differential diagnoses to exclude:

• Syphilis - typically presents with painless ulcers (chancres), though atypical presentations occur 2, 3
• Chancroid - painful ulcers with tender inguinal adenopathy 2, 3
• Non-infectious causes - sexual trauma, Behçet syndrome, fixed drug eruption, aphthous ulcers (ulcus vulvae acutum) 2, 3, 5

Empiric Treatment Strategy

For first episode of genital HSV:

• Acyclovir 400 mg orally three times daily for 7-10 days, OR 3
• Valacyclovir 1 g orally twice daily for 7-10 days, OR 3
• Famciclovir 250 mg orally three times daily for 7-10 days 3

For recurrent episodes:

• Same medications but shorter duration of 5 days 3

If diagnosis is uncertain and patient is in a community where chancroid or syphilis is prevalent:

• Consider empiric treatment for syphilis with benzathine penicillin G 2.4 million units IM single dose 1
• In chancroid-endemic areas, add ceftriaxone 250 mg IM single dose or azithromycin 1 g orally single dose 3

Critical Follow-Up and Reassessment

Reassess at 48-72 hours if no clinical improvement occurs. 2 At this point, reconsider alternate diagnoses including:

• Behçet syndrome 2, 3
• Crohn disease 1, 2
• Fixed drug eruption 2, 3
• Sexual trauma 2, 3
• Ulcus vulvae acutum (non-sexually transmitted aphthous ulcers, often following viral illnesses like influenza or EBV) 5, 6

Important caveat: Up to 25% of genital ulcers have no identifiable pathogen even after complete testing, making clinical judgment essential. 2, 3

Common Pitfalls to Avoid

• Never rely on a single positive test to exclude other pathogens - up to 10% of patients have HSV co-infected with T. pallidum 2
• Do not delay treatment while awaiting test results - empiric therapy based on clinical presentation is appropriate and recommended 1
• Do not assume all genital ulcers are sexually transmitted - non-infectious causes like aphthous ulcers can occur after viral illnesses (influenza, EBV) without sexual transmission 5, 6
• Avoid missing lichen sclerosus - if lesions are more white plaques than ulcers, particularly in postmenopausal women, consider biopsy to rule out lichen sclerosus which carries malignant transformation risk 7

Adjunctive Symptomatic Management

• Topical lidocaine gel for pain relief 7, 5
• Advise avoidance of sexual activity until ulcers heal completely 1
• Gentle hygiene with mild, unscented cleansers 2

Partner Management

Sex partners should be evaluated and treated if contact occurred within 60 days preceding symptom onset. 1 Partners should receive the same treatment regimen if HSV or syphilis is confirmed. 1