What is the differential diagnosis for a patient presenting with a papule on the labia minora for a few days?

Differential Diagnosis of Papule on Labia Minora

The differential diagnosis for a papule on the labia minora present for a few days includes infectious etiologies (genital warts, herpes simplex virus, syphilis, Bartholin gland infection), inflammatory conditions (lichen sclerosus, vulvar Fordyce adenitis), and less common entities (atypical melanocytic nevus, demodicosis). 1

Infectious Etiologies (Most Common in Acute Presentation)

Sexually Transmitted Infections

• Genital warts (condylomata acuminata) caused by HPV types 6 or 11 present as flat or exophytic papules that can be diagnosed by visual inspection alone, without requiring biopsy unless the diagnosis is uncertain, the lesions are pigmented, indurated, fixed, or ulcerated 1
• Herpes simplex virus typically causes vesicles and pustules that rapidly progress to painful ulcers, though early presentation may show intact papules; viral culture for HSV should be performed for suspicious lesions 1
• Secondary syphilis manifests as condylomata lata—flesh-colored papules on mucous membranes filled with spirochetes that can be confused with warts; serologic tests for syphilis are essential 1

Bartholin Gland Pathology

• Bartholin gland infection or abscess presents with swelling, erythema, and tenderness extending into the entire labia minora, located specifically at the 4 and 8 o'clock positions in the posterior vestibule 1, 2
• Any vaginal organism can cause infection, but STI pathogens including gonorrhea and chlamydia are common culprits requiring nucleic acid amplification testing 1, 2

Inflammatory/Dermatologic Conditions

Lichen Sclerosus

• Presents as porcelain-white papules and plaques with areas of ecchymosis affecting the interlabial sulci and labia minora, though this typically has a more chronic course than "a few days" 1, 3
• Has a bimodal age distribution with peaks in prepubertal girls and postmenopausal women 1, 3
• Main symptom is intractable pruritus, often worse at night, with pain occurring when erosions or fissures develop 1, 3

Vulvar Fordyce Adenitis (Vulvar Acne)

• Recurrent painful papules, pustules, or nodules on the labia minora and inner labia majora, often with suppuration and eventual pitted scarring 4, 5
• Median age at diagnosis is 36 years, with many patients experiencing premenstrual exacerbation 4, 5
• Histology shows folliculocentric microabscess formation with acute and chronic inflammatory infiltrate 5

Less Common Entities

• Atypical melanocytic nevus of genital type appears as a slightly raised tan-brown papule with somewhat irregular borders, often detected incidentally during gynecologic examination 6
• Vulvar demodicosis presents as tender red papules on the labia minora that arise and drain over 24-72 hours, caused by Demodex folliculorum infestation of Fordyce spots 7

Critical Diagnostic Algorithm

Immediate Assessment Points

• Location specificity: Bartholin gland pathology occurs at 4 and 8 o'clock positions; other conditions are more diffusely distributed on the labia minora 1, 2
• Lesion characteristics: Note whether the papule is flesh-colored, pigmented, white, or erythematous; assess for vesiculation, ulceration, or discharge 1
• Associated symptoms: Determine presence of pain, pruritus, or cyclical pattern related to menstruation 4, 5

Essential Testing

• For suspected STI: Perform viral culture for HSV and serologic tests for syphilis when ulcers or suspicious papules are present 1
• For glandular involvement: Obtain gonorrhea and chlamydia nucleic acid amplification tests when Bartholin or Skene gland infection is suspected 1, 2
• Biopsy indications: Consider biopsy if the diagnosis is uncertain, lesions do not respond to standard therapy, the patient is immunocompromised, or lesions are pigmented, indurated, fixed, and ulcerated 1

Common Pitfalls to Avoid

• Do not assume all labial papules are benign cysts—always assess for STI pathogens when glandular infections are present, as multiple organisms including gonorrhea and chlamydia commonly cause Bartholin gland pathology 1, 2
• Do not dismiss pigmented lesions without proper evaluation, as atypical melanocytic nevi of genital type can be confused with dysplastic nevi or malignant melanoma 6
• Consider that multiple etiologies can coexist—a patient may have both HSV and bacterial superinfection requiring concurrent treatment 2
• Do not overlook lichen sclerosus in prepubertal girls, as ecchymosis may be mistakenly attributed to sexual abuse rather than this autoimmune condition 8, 3