What is the appropriate evaluation and management for a patient presenting with a penile rash or sore?

Evaluation and Management of Penile Rash or Sore

A male patient presenting with a penile rash or sore should be immediately evaluated for sexually transmitted infections (STIs), particularly genital herpes (HSV), syphilis, and human papillomavirus (HPV), with laboratory confirmation essential because clinical examination alone cannot reliably distinguish between causes. 1

Initial Diagnostic Approach

Sexual History and Lesion Documentation

• Obtain detailed sexual history including all contacts within the preceding 60 days 2
• Document specific lesion characteristics: vesicular versus ulcerative versus papular, exact location, and distribution pattern 1
• Ask about timing of lesion onset, associated symptoms (pain, discharge, systemic symptoms), and any prior similar episodes 1

Physical Examination Findings to Document

• Vesicular lesions progressing to shallow ulcers suggest genital herpes (HSV), the most common cause of sexually acquired genital ulceration 2, 1
• Painless ulcer with indurated borders suggests primary syphilis (chancre) 1
• Papular or cauliflower-like lesions suggest genital warts (HPV types 6 or 11) 1
• Examine for urethral discharge, which may indicate concurrent urethritis requiring additional testing 2

Essential Laboratory Testing

First-Line STI Testing (Mandatory)

• Swab vesicular fluid or ulcer base for HSV PCR, viral culture, or direct fluorescent antibody testing 2, 1
• Syphilis serology (RPR or VDRL with confirmatory treponemal testing if positive) 1
• Nucleic acid amplification test (NAAT) for N. gonorrhoeae and C. trachomatis from urethral swab or first-void urine 2, 1
• HIV counseling and testing 2, 1

Additional Testing Based on Clinical Presentation

• If urethral discharge is present: Gram stain of urethral exudate looking for white blood cells and gram-negative intracellular diplococci 2
• If lesions are atypical, pigmented, indurated, fixed, or ulcerated: consider biopsy to exclude malignancy 1
• Occasionally HSV and T. pallidum can be recovered from the same lesion, so test for both even if one seems more likely 2, 1

Empiric Treatment Strategy

When to Treat Empirically

Empiric treatment without waiting for laboratory results is recommended only for patients at high risk for infection who are unlikely to return for follow-up evaluation. 2

Empiric Regimen for High-Risk Patients

If urethritis is documented or strongly suspected and patient may not return:

• Ceftriaxone 250 mg IM single dose (for gonorrhea) 3
• PLUS Azithromycin 1 g orally single dose (for chlamydia) 2, 3

This dual therapy addresses the most common bacterial STIs and should be given on-site with directly observed administration 2, 3

Lesion-Specific Treatment (After Confirmation)

• Genital herpes: Antiviral therapy (acyclovir, valacyclovir, or famciclovir) should be initiated based on clinical suspicion while awaiting laboratory confirmation 2
• Syphilis: Benzathine penicillin G 2.4 million units IM single dose for primary syphilis 1
• Genital warts: Treatment options include provider-applied therapies (cryotherapy, podophyllin) or patient-applied therapies (imiquimod, podofilox); biopsy rarely needed unless diagnosis uncertain 1

Partner Management and Follow-Up

Partner Notification and Treatment

• All sex partners within the preceding 60 days must be evaluated, tested, and treated empirically 2
• If last sexual contact was more than 60 days before symptom onset, treat the most recent partner 2
• Partners should receive the same empiric treatment regimen even if asymptomatic 3

Sexual Activity Restrictions

• Patient must abstain from all sexual intercourse for 7 days after initiating treatment and until all symptoms have resolved 2
• Patient must abstain until all sex partners have completed treatment to prevent reinfection 2, 3

Follow-Up Instructions

• Return for evaluation if symptoms persist or recur after completing therapy 2
• Symptoms alone without objective signs of inflammation are not sufficient basis for re-treatment 2
• Retest at 3 months for chlamydia if initially positive, as reinfection rates are high (up to 39% in some populations) 3

Critical Pitfalls to Avoid

• Do not rely on physical examination alone to diagnose genital lesions—most HSV infections present with mild, atypical lesions that cannot be diagnosed clinically 1
• Do not assume a single etiology—HSV and syphilis can coexist in the same lesion 2, 1
• Do not delay syphilis testing—all patients with genital rash require syphilis serology regardless of lesion appearance 1
• Do not forget to test for HIV—genital ulcerative disease facilitates HIV transmission 2
• Do not treat partners based on patient report alone—directly verify treatment or use expedited partner therapy 3
• Do not perform test-of-cure for chlamydia or gonorrhea in asymptomatic patients treated with recommended regimens, as cure rates exceed 97% 3

Non-Infectious Differential Diagnoses

If STI testing is negative and lesions persist, consider:

• Fixed drug eruption (mucosal ulcerations mimicking herpes) 1
• Behçet syndrome (recurrent oral and genital ulcers) 2, 1
• Inflammatory bowel disease (Crohn disease can cause genital ulceration) 2, 1
• Herpes zoster (shingles in genital dermatome) 1

Biopsy should be performed if diagnosis remains uncertain, lesions fail to respond to appropriate therapy, or malignancy is suspected 1