What is the cause and appropriate treatment for a fluid-filled, moderate-sized blister on the shaft of the penis in a sexually active patient?

Fluid-Filled Blister on Penile Shaft: Diagnosis and Management

Immediate Assessment

A moderate-sized, fluid-filled blister on the penile shaft in a sexually active patient most likely represents either friction-induced trauma, genital herpes (HSV), or less commonly, a fixed drug eruption—and your first priority is to distinguish between infectious and non-infectious causes through targeted history and examination. 1, 2

Critical Red Flags to Rule Out First

Before addressing the blister itself, you must exclude emergencies:

• Fournier gangrene: Look for fever, severe pain disproportionate to exam findings, crepitus, or rapidly progressive skin necrosis—this requires immediate surgical debridement and broad-spectrum antibiotics 3, 1
• Penile fracture: Ask about trauma during intercourse, a cracking/snapping sound, immediate detumescence, and look for ecchymosis extending beyond the blister 1
• Abscess formation: Assess for fluctuance, severe tenderness, or systemic signs of infection 3, 4

Most Likely Diagnosis: Friction Blister vs. Genital Herpes

If the Blister Appears Traumatic (Friction-Induced)

For a single, clear fluid-filled blister without surrounding vesicles, occurring after vigorous sexual activity, the most likely diagnosis is a friction blister or nonvenereal sclerosing lymphangitis. 5

Management approach:

• Leave small to medium blisters intact—the blister roof provides a natural sterile dressing 3
• If the blister is large and tense, puncture and drain it with a sterile needle, but leave the roof in place to protect the underlying dermis 3
• If already ruptured, remove only loose, non-adherent skin 3
• Apply nonadherent dressing to prevent secondary bacterial infection 3
• Recommend sexual abstinence for 2-3 weeks until complete healing 5
• Reassurance: Friction blisters typically resolve completely within 2-3 weeks without intervention 5

If Vesicular Pattern Suggests Herpes

If you see multiple small vesicles clustered together, or if the blister progresses to shallow ulceration, genital herpes (HSV) becomes the primary concern. 2

Diagnostic confirmation is mandatory because clinical examination alone cannot reliably distinguish HSV from other causes:

• Swab the vesicular fluid or ulcer base for HSV PCR (preferred) or viral culture 2
• Obtain syphilis serology—HSV and Treponema pallidum can coexist in the same lesion 2
• HIV counseling and testing should be offered 3, 2

Treatment for confirmed or highly suspected HSV:

• Acyclovir 400 mg orally three times daily for 7-10 days (first episode)
• Valacyclovir 1 g orally twice daily for 7-10 days (alternative)
• Famciclovir 250 mg orally three times daily for 7-10 days (alternative)

When to Suspect Bacterial Superinfection

If the blister shows surrounding erythema, warmth, purulent drainage, or the patient develops fever, bacterial cellulitis or abscess must be considered. 3, 4

For Sexually Active Patients <35 Years:

• Ceftriaxone 250 mg IM once PLUS doxycycline 100 mg orally twice daily for 10 days 1
• This covers N. gonorrhoeae and C. trachomatis 1

For Patients ≥35 Years or Enteric Organism Concern:

• Ofloxacin 300 mg orally twice daily for 10 days OR levofloxacin 500 mg orally once daily for 10 days 1

Before Starting Antibiotics:

• Obtain Gram stain and culture of any purulent material 3, 1
• NAAT testing for N. gonorrhoeae and C. trachomatis 1
• Mandatory reassessment at 72 hours—if no improvement, consider abscess requiring surgical drainage 1

If Candidal Balanitis is Suspected

If the blister is accompanied by erythematous patches on the glans with pruritus, consider candidal balanitis. 1, 6

• Clotrimazole 1% cream or miconazole 2% cream applied 1-3 times daily for 7-14 days 1
• Oral fluconazole 150 mg single dose for more widespread involvement 1
• Treat sexual partners if recurrent infections occur 1

Common Pitfalls to Avoid

• Do not delay surgical consultation if you suspect Fournier gangrene, penile fracture, or abscess—these require urgent intervention 3, 1
• Do not assume all genital blisters are HSV—friction trauma and fixed drug eruptions can mimic herpes 2, 5
• Do not forget to evaluate and treat sexual partners for STI-related causes to prevent reinfection 3, 1
• Do not use empiric antibiotics without obtaining cultures first unless the patient is systemically ill 3, 1
• Do not rupture small blisters unnecessarily—intact blisters heal faster and have lower infection rates 3

Follow-Up Strategy

• Reassess at 3-5 days to ensure improvement 1
• If no improvement or worsening, consider biopsy to rule out malignancy, atypical infection, or inflammatory dermatosis 3, 2
• Sexual abstinence until complete healing and partner treatment completed 3, 1