Differential Diagnosis of Painful Filled Small Nodules on Labia Minora
The most likely causes of painful filled small nodules on the labia minora are Bartholin gland abscess/cyst, vulvar Fordyce adenitis (vulvar acne), infected epidermal cysts, or herpes simplex virus vesicles/pustules.
Primary Infectious Etiologies
Bartholin Gland Pathology
- Bartholin gland abscesses present with swelling, erythema, and tenderness that can extend into the entire labia minora, located at the 4 and 8 o'clock positions in the posterior vestibule 1
- These glands are commonly infected by STI pathogens including gonorrhea and chlamydia, though any vaginal organism can cause infection 1
- Bartholin duct cysts develop from ductal blockage and affect 2% of women in their lifetime 2
- The filled nodules are typically unilateral and can progress from cyst to abscess if infected 2
Herpes Simplex Virus
- HSV commonly causes painful vesicles and pustules on the external genitalia that can present as fluid-filled lesions 1
- Viral culture for HSV should be performed for suspicious lesions 1
- These lesions are typically accompanied by ulceration as vesicles rupture 1
Secondary Syphilis
- Condylomata lata appear as flesh-colored papules on mucous membranes that are filled with spirochetes 1
- These can be confused with warts but represent a manifestation of secondary syphilis 1
- Serologic tests for syphilis should be performed for suspicious lesions 1
Non-Infectious Inflammatory Causes
Vulvar Fordyce Adenitis
- This condition presents as recurrent painful papules, pustules, or nodules primarily on the labia minora and inner labia majora 3
- The median age at diagnosis is 36 years with a median time to diagnosis of 6.5 years, indicating frequent misdiagnosis 3
- Suppuration occurs in approximately half of cases, and pitted scars develop in some patients 3
- Neutrophilic infiltrates are observed within or around Fordyce sebaceous glands on biopsy 3
- Associated acne vulgaris is present in 65% of cases where data are available 3
Epidermal Cysts
- Epidermal cysts can present as tumors or swellings above the labia minora 4
- These are typically solitary, filled lesions that can become painful if infected 4
Critical Diagnostic Algorithm
Immediate Assessment Points
- Location matters: Bartholin gland pathology occurs at 4 and 8 o'clock positions in the posterior vestibule, while Fordyce adenitis and epidermal cysts occur more diffusely on the labia minora 1, 3
- Assess for recurrent episodes: Fordyce adenitis characteristically recurs over years, while Bartholin abscesses may be isolated events 3
- Document associated findings: suppuration, scarring, or systemic symptoms 3
Mandatory Testing
- STI testing including gonorrhea and chlamydia nucleic acid amplification tests must be performed when Bartholin or Skene gland involvement is suspected 1, 5
- Viral culture for HSV when vesicular lesions are present 1, 5
- Serologic testing for syphilis if papular lesions are noted 1, 5
Common Pitfalls to Avoid
- Do not assume all labial nodules are simple cysts—always assess for STI pathogens when glandular infections are present 1, 6
- Avoid dismissing recurrent painful nodules as simple folliculitis; consider vulvar Fordyce adenitis, which has a median 6.5-year delay to diagnosis 3
- Do not perform simple needle aspiration or incision and drainage for Bartholin pathology, as these have higher recurrence rates compared to fistulization or marsupialization 2
- Consider that multiple etiologies can coexist—a patient may have both HSV and bacterial superinfection 1
Treatment Considerations Based on Etiology
For Suspected Bartholin Gland Infection
- Ceftriaxone 250 mg IM single dose PLUS Doxycycline 100 mg orally twice daily for 10 days when gonorrhea or chlamydia is suspected 5
- Definitive management requires fistulization, marsupialization, or sclerotherapy rather than simple drainage 2