What to do for persistent genital itching with negative STI (Sexually Transmitted Infections) panel, no trichomoniasis, no bacterial vaginosis, no chlamydia, and no gonorrhea?

Evaluation and Management of Genital Itching with Negative STI Testing

With all STI testing negative, the most likely diagnoses are vulvovaginal candidiasis (yeast infection), contact/irritant dermatitis, or lichen sclerosis, and empiric treatment with topical antifungal therapy is the appropriate first-line approach. 1

Diagnostic Approach

Most Common Non-STI Causes of Genital Itching

The differential diagnosis when STI testing is negative includes:

• Vulvovaginal candidiasis (VVC): Characterized by pruritus, vulvovaginal erythema, white discharge, and burning. This is the most common infectious cause when STI testing is negative. 1, 2
• Contact or irritant dermatitis: Caused by soaps, detergents, perfumes, or tight clothing. Look for erythema without discharge. 3
• Lichen sclerosis or other dermatologic conditions: Presents with white plaques, skin changes, and intense itching. 4
• Residual symptoms from treated infection: Pruritus may persist for several weeks even after successful treatment. 1

Key Clinical Features to Assess

Examine for the following specific findings:

• Discharge characteristics: White, thick discharge suggests candidiasis; absence of discharge points toward dermatitis. 2
• Vulvar examination: Look for erythema, excoriation from scratching, white plaques (lichen sclerosis), or skin thickening. 5
• pH testing: Vaginal pH >4.5 suggests BV or trichomoniasis (already ruled out); pH <4.5 supports candidiasis. 1
• KOH preparation: Microscopy showing yeast or pseudohyphae confirms candidiasis. 1

Treatment Recommendations

First-Line Empiric Therapy: Topical Antifungals

Even without confirmed yeast on microscopy, empiric treatment for vulvovaginal candidiasis is appropriate given the high prevalence and the fact that microscopy misses 20-50% of cases. 1

Recommended Antifungal Regimens (choose one):

• Clotrimazole 1% cream: 5g intravaginally for 7 days 1, 6
• Clotrimazole 100mg vaginal tablet: One tablet for 7 days 1
• Miconazole 2% cream: 5g intravaginally for 7 days 1
• Fluconazole 150mg oral: Single dose (most convenient option) 1

For external vulvar itching: Apply clotrimazole cream to external skin twice daily for up to 7 days. 6

Second-Line: Topical Corticosteroids for Dermatitis

If antifungal therapy fails after 7 days, consider contact/irritant dermatitis:

• Hydrocortisone 1% cream: Apply to affected external areas 3-4 times daily for up to 2 weeks. 3
• Important caveat: Do not use corticosteroids intravaginally or if yeast infection is still suspected, as this can worsen candidiasis. 3

Follow-Up Strategy

When to Reassess

• If symptoms persist after 2 weeks of antifungal treatment: Return for re-examination and consider culture for Candida species (including non-albicans species like C. glabrata that may be azole-resistant). 1
• If symptoms recur within 2 months: Seek medical evaluation to rule out recurrent VVC (defined as ≥4 episodes per year) or alternative diagnoses. 1

Additional Testing if Initial Treatment Fails

• Fungal culture: To identify non-albicans Candida species (present in 10-20% of recurrent cases) that may require longer treatment duration. 1
• Consider underlying conditions: Uncontrolled diabetes, immunosuppression, or HIV infection predispose to complicated VVC. 1
• Dermatology referral: If skin changes suggest lichen sclerosis or other dermatologic conditions. 5, 4

Partner Management

Sexual partner treatment is NOT recommended for vulvovaginal candidiasis, as it is not sexually transmitted. 1 However, a minority of male partners may develop symptomatic balanitis (penile irritation) and can be treated with topical antifungals if symptomatic. 1

Common Pitfalls to Avoid

• Over-reliance on microscopy: Negative microscopy does not rule out candidiasis; empiric treatment is still appropriate. 1
• Premature use of corticosteroids: Using topical steroids before ruling out or treating yeast infection can worsen candidiasis. 3
• Ignoring non-infectious causes: Chemical irritants (soaps, douches, perfumed products) are common culprits that require behavioral modification, not medication. 5
• Treating partners unnecessarily: VVC does not require partner treatment unless the partner is symptomatic. 1

Special Considerations

If Patient is Pregnant

• Only topical azole therapy for 7 days: Oral fluconazole should be avoided during pregnancy. 1
• Preferred agents: Clotrimazole, miconazole, or terconazole for 7 days. 1

If Recurrent Episodes (≥4 per year)

• Longer initial treatment: 7-14 days of topical therapy or fluconazole 150mg on days 1 and 4. 1
• Maintenance therapy: After achieving remission, use suppressive therapy (fluconazole 150mg weekly or clotrimazole 500mg weekly) for 6 months. 1