Treatment of Painful Nodules and Pustules on the Labia Minora with Negative STI Testing
The most likely diagnosis is vulvar Fordyce adenitis (also called vulvar acne), and treatment should begin with oral tetracyclines (doxycycline 100 mg twice daily), with escalation to oral isotretinoin for refractory cases. 1, 2
Clinical Recognition and Diagnosis
This presentation represents a distinct clinical entity affecting the labia minora and inner labia majora, characterized by:
- Recurrent painful papules, pustules, or nodules specifically on the labia minora (most common site) or inner labia majora 2
- Suppuration and drainage occurring over 24-72 hour periods, often multiple times per week 3
- Pitted scarring may develop from chronic inflammation 2
- Cyclical pattern with premenstrual exacerbation reported in approximately half of patients 1
The median time to diagnosis is 6.5 years, indicating this condition is frequently misdiagnosed 2. The median age at presentation is in the early-to-mid 30s (range 21-45 years) 1, 2.
Histopathologic Features
When biopsy is performed, expect:
- Folliculocentric microabscess formation surrounded by acute and chronic inflammatory infiltrates 1
- Focal foreign-body granulomatous reaction 1
- Neutrophilic infiltrates within or around Fordyce sebaceous glands 2
Treatment Algorithm
First-Line Therapy
Oral tetracyclines are the initial treatment of choice 1, 2:
- Doxycycline 100 mg orally twice daily
- Continue for several months to assess response
- Note: Tetracyclines show inconsistent effectiveness 2
Second-Line Therapy
Oral isotretinoin for patients unresponsive to tetracyclines 2:
- Led to complete remission in patients who failed tetracycline therapy 2
- Standard acne dosing protocols apply
- This represents the most effective option for refractory cases 2
Alternative Considerations
Antiandrogenic therapy may be effective, particularly if associated features suggest hyperandrogenism 1:
- Consider in patients with concurrent acne vulgaris (seen in approximately 65% of cases where data available) 2
- May be appropriate for patients with hirsutism or androgenic alopecia 2
Oral zinc has been tried but shows inconsistent results 2
Important Differential Diagnoses to Exclude
Infectious Causes Already Ruled Out
With negative STI testing, you have appropriately excluded 4:
- Bartholin gland infection (gonorrhea/chlamydia)
- Herpes simplex virus
- Syphilis
Consider Rare Infectious Cause
Symptomatic vulvar demodicosis presents identically but is exceedingly rare 3:
- Tender red bumps that arise and drain over 24-72 hours
- Diagnosis requires biopsy showing Demodex mites in Fordyce spots 3
- Treatment: oral ivermectin plus topical metronidazole 3
- Consider if standard acne treatments fail
Non-Infectious Inflammatory Conditions
Lichen sclerosus presents differently and should not be confused 4:
- Porcelain-white papules and plaques (not pustules)
- Primary symptom is itch, not recurrent painful nodules 4
- Affects interlabial sulci with characteristic appearance 4
Critical Clinical Pitfalls
Do not mistake this for hidradenitis suppurativa, though the two conditions can coexist (seen in 3 of 45 patients in one cohort) 2. The anatomic distribution on labia minora (site of Fordyce granules) rather than intertriginous areas helps distinguish vulvar Fordyce adenitis.
Do not dismiss as simple folliculitis requiring only topical therapy—this condition requires systemic treatment for adequate control 1, 2.
Do not assume STI despite vulvar location when testing is negative and clinical features match this distinct pattern 2.