What is the cause and treatment of penile shaft blisters and pain, potentially related to a previous sexually transmitted infection (STI)?

Penile Shaft Blisters and Pain: Diagnosis and Treatment

Most Likely Diagnosis

Penile shaft blisters with pain most likely represent genital herpes simplex virus (HSV) infection, which presents as vesicles that burst to form shallow ulcers, typically lasting less than 10 days. 1

Diagnostic Approach

Key Clinical Features to Identify

• Vesicular lesions that progress to shallow ulcers or erosions, eventually crusting and healing without scars, are pathognomonic for HSV infection 1
• The presence of vesicular and/or ulcerative lesions on the penis, buttocks, or perineum in males warrants immediate testing for genital herpes 1
• A history of recurrent vesicular and ulcerative genital skin lesions strongly suggests HSV as the causative agent 1

Laboratory Confirmation Required

• Clinical diagnosis alone is unreliable—laboratory confirmation should always be sought because HSV can be confused with syphilis (Treponema pallidum), chancroid (Haemophilus ducreyi), or non-infectious causes like Behçet syndrome or inflammatory bowel disease 1
• Collect vesicle fluid by opening vesicles with a sterile needle and swabbing the content for viral culture or nucleic acid amplification testing (NAAT) 1
• Test for co-infections: syphilis serology and HIV counseling/testing are mandatory, as genital ulceration indicates risk for multiple sexually transmitted infections 1, 2

Treatment Protocol

Antiviral Therapy for Genital Herpes

While the provided guidelines focus on diagnostic procedures rather than specific HSV treatment regimens, the standard approach for first-episode genital herpes involves:

• Immediate antiviral therapy should be initiated based on clinical presentation while awaiting laboratory confirmation, as episodes typically last less than 10 days but may be prolonged by secondary bacterial infection 1
• Treatment addresses the life-long nature of HSV infection and prevents serious complications including HIV transmission risk 1

Adjunctive Measures

• Pain management with analgesics during the acute phase 3, 2
• Keep lesions clean and dry to prevent secondary bacterial infection 1

Critical Differential Diagnoses to Exclude

Testicular/Epididymal Pathology

• If pain is sudden and severe, immediately rule out testicular torsion, which is a surgical emergency requiring specialist consultation within hours to preserve testicular viability 1, 3, 2
• Epididymitis presents with unilateral testicular pain and swelling but typically lacks vesicular lesions on the penile shaft itself 3, 2

Bacterial Cellulitis or Abscess

• Penile shaft cellulitis presents with diffuse swelling, erythema, warmth, and tenderness but typically without vesicles 4, 5
• Streptococcus species can cause penile cellulitis with potential abscess formation, requiring broad-spectrum intravenous antibiotics 4, 5

Other STIs

• Syphilis can present with genital ulceration and occasionally co-exists with HSV in the same lesion 1
• Perform syphilis serology on all patients with genital ulceration 1, 2

Partner Management and Prevention

• All sexual partners from the 60 days preceding symptom onset must be evaluated and treated if HSV or other STI is confirmed 3, 2, 6
• Abstain from all sexual intercourse until both patient and partners complete treatment and are symptom-free 3, 2, 6
• Failure to treat partners perpetuates reinfection cycles and transmission 6

Red Flags Requiring Immediate Action

• Sudden, severe pain warrants emergency evaluation for testicular torsion 1, 3, 2
• No improvement within 3 days of treatment initiation requires reevaluation of diagnosis and therapy 1, 3
• Persistent lesions despite treatment may indicate immunosuppression, requiring evaluation for HIV and consideration of fungal or mycobacterial causes 1, 2
• Unexplained rash, ulceration, and induration that worsens despite anti-inflammatory or antiviral treatment should raise suspicion for rare malignancies like angiosarcoma, warranting biopsy 7

Common Pitfalls to Avoid

• Never rely on clinical diagnosis alone—HSV, syphilis, and other causes of genital ulceration can appear identical, and laboratory confirmation is essential 1
• Don't assume all genital pain is infectious—always exclude testicular torsion first, especially in younger patients or when pain onset is acute 1, 3, 2
• Don't neglect partner notification—untreated partners perpetuate transmission and reinfection 3, 6