What is the differential diagnosis for vaginal labia ulcers?

Differential Diagnosis for Vaginal Labia Ulcers

The most common cause of labial ulcers in the United States is herpes simplex virus (HSV), followed by syphilis, and your diagnostic workup must include testing for both plus HIV, as clinical diagnosis alone is unreliable and up to 10% of patients have co-infections. 1

Infectious Causes (Most Common)

Sexually Transmitted Infections

Primary infectious etiologies:

• HSV (most common): Presents as vesicles that burst forming shallow ulcers on the vulva and labia, progressing from papules to vesicles to ulcers that crust and heal within less than 10 days 1, 2

• Syphilis (second most common): Causes painless ulcers (chancres) 1

• Chancroid (Haemophilus ducreyi): Painful ulcers with tender inguinal adenopathy; suppurative adenopathy is almost pathognomonic 1

• Lymphogranuloma venereum (LGV): Caused by Chlamydia trachomatis serovars L1, L2, or L3; causes ulcers at inoculation site but rare in the United States 3, 1

• Granuloma inguinale (donovanosis): Caused by Klebsiella granulomatis; progressive ulcerative lesions, uncommon in the United States 3

Other Viral Causes

• Epstein-Barr virus (EBV): Can cause vulvar ulcers during acute primary infection and is NOT sexually transmitted, making it critical to consider in patients where STI diagnosis has psychosocial consequences 4

• Cytomegalovirus (CMV): Identified as a cause in microbiological workup 5

• Parvovirus B19: Rare but documented cause 5

• Mycoplasma pneumoniae: Should be considered in serology workup 5

Non-Infectious Causes

Non-venereal etiologies to exclude:

• Lipschütz ulcers: Acute, painful, non-sexually transmitted ulcers often preceded by non-gynecological symptoms (fever, malaise) in the week before; most commonly on vestibule (57.6%) and labia minora (30.3%); recurrence occurs in 30% of cases 5, 6

• Behçet syndrome: Autoimmune condition causing recurrent oral and genital ulcers 1, 2

• Crohn disease: Extraintestinal manifestation presenting as vulvar ulceration 1, 2

• Fixed drug eruption: Medication-induced ulceration 1, 2

• Sexual trauma: Direct mechanical injury 1

Essential Diagnostic Testing Algorithm

Mandatory initial workup for ALL labial ulcers:

1. HSV testing: Viral culture or antigen test from ulcer base or vesicular fluid 1, 2

2. Syphilis serology: Non-negotiable in all cases 1, 2

3. Darkfield microscopy or direct fluorescent antibody testing for Treponema pallidum 1

4. Testing for Chlamydia trachomatis and Neisseria gonorrhoeae 1, 2

5. HIV testing: Especially in patients with syphilis or chancroid 1

6. Culture for Haemophilus ducreyi in high-prevalence settings 1

Critical Clinical Pitfalls

Avoid these common diagnostic errors:

• Co-infection is common: Up to 10% of genital ulcer patients have HSV co-infected with Treponema pallidum 1, 2

• Clinical diagnosis is unreliable: Laboratory confirmation is mandatory because clinical presentation is often nonspecific 1, 2, 7

• 25% remain undiagnosed: Even after complete evaluation, at least 25% of genital ulcers have no laboratory-confirmed diagnosis 1, 2

• Consider non-STI causes in specific populations: Lipschütz ulcers occur in women of any age (mean 29 years), most sexually active, but NOT sexually transmitted 5, 6

• Look for systemic symptoms: 75.7% of Lipschütz ulcer patients have non-gynecological symptoms (fever, malaise) in the week before ulcer appearance 5

High-Risk Populations Requiring Enhanced Vigilance

Specific groups with increased STI prevalence:

• Men who have sex with men (MSM) 8
• Sex workers 8
• Sex tourists 8
• Consider atypical locations (oral cavity, rectum) and presentations (pelvic pain with LGV) in these populations 8