What are the differential diagnoses for a recurrent pruritic penile ulcer that occurs once or twice a year in an older man?

Differential Diagnoses for Recurrent Pruritic Penile Ulcer in an Older Man

Recurrent genital herpes simplex virus (HSV) infection is the most likely diagnosis for a penile ulcer occurring once or twice yearly with associated itching in an older male. 1

Primary Differential: Recurrent Genital Herpes

Recurrent HSV infection characteristically presents with episodes occurring at varying frequencies—from once every few years to several times per month—with the localization of recurrent lesions typically coinciding with the primary infection site. 1

Key Clinical Features Supporting HSV:

• The classic recurrence pattern begins with erythema, progresses to papules then vesicles, which burst to form shallow ulcers that heal spontaneously without scarring within less than 10 days 1
• Pruritus is a recognized symptom of genital HSV, particularly during the vesicular stage 1
• The annual or biannual frequency described fits the typical pattern of recurrent herpetic infection, which can range from once every few years to multiple times monthly 1

Diagnostic Approach for HSV:

• Culture or antigen testing for HSV from the ulcer base or vesicular fluid is essential for laboratory confirmation 1
• Direct immunofluorescence testing or darkfield examination should be performed to exclude other causes 1
• Serologic testing for syphilis must be performed in all patients with genital ulcers 1

Other Critical Differentials to Exclude

Syphilis (Treponema pallidum)

• Primary syphilitic chancres are typically painless, but recurrent manifestations can occur 1
• Darkfield examination or direct immunofluorescence for T. pallidum is required, along with serologic testing performed at least 7 days after ulcer onset 1
• HSV and T. pallidum can occasionally be recovered from the same lesion, necessitating testing for both 1

Fixed Drug Eruption

• Fixed drug eruption presents as oval-circular erythematous patches with itching and burning pain, commonly affecting the anogenital area 2
• This diagnosis requires careful medication history, as lesions recur at the same site with re-exposure to the offending drug (commonly trimethoprim-sulfamethoxazole, NSAIDs, or antibiotics) 2
• Post-inflammatory hyperpigmentation typically develops after resolution, which can help distinguish this from HSV 2

Behçet Syndrome

• Behçet syndrome causes recurrent painful genital ulcers that can mimic infectious etiologies 1
• This diagnosis should be considered when infectious workup is negative and ulcers are associated with oral ulcers, ocular inflammation, or other systemic manifestations 1

Lichen Sclerosus (Balanitis Xerotica Obliterans)

• Lichen sclerosus presents as atrophic white patches on the glans penis and foreskin, though ulceration can occur with trauma or secondary infection 3, 4
• Biopsy is essential for definitive diagnosis due to risk of progression to squamous cell carcinoma 3, 4
• Treatment requires topical clobetasol propionate 0.05% cream twice daily for 2-3 months with long-term follow-up 3

Candidal Balanitis

• Candidal balanitis typically presents with erythematous areas on the glans with pruritus, but ulceration is less common 3
• This is more likely in diabetic or immunocompromised patients 3
• First-line treatment includes topical miconazole 2% cream twice daily for 7 days 3

Chancroid (Haemophilus ducreyi)

• Chancroid presents with painful genital ulcers, though recurrent episodes are uncommon 1
• Culture on special media is required for diagnosis, though sensitivity is typically less than 80% 1
• The combination of painful ulcer with tender inguinal adenopathy is suggestive 1

Essential Diagnostic Workup

At minimum, all patients with recurrent genital ulcers require:

• HSV culture or antigen testing from the ulcer base 1
• Serologic testing for syphilis 1
• HIV testing, as genital ulcers increase HIV transmission risk and HIV infection can alter disease presentation 1
• Consideration of biopsy for lesions that are pigmented, indurated, fixed, or ulcerated to exclude malignancy, particularly lichen sclerosus or squamous cell carcinoma 3, 4

Critical Pitfalls to Avoid

• Do not rely on clinical diagnosis alone—at least one quarter of patients with genital ulcers have no laboratory-confirmed diagnosis even after complete testing 1
• Do not assume a single etiology—HSV and T. pallidum can coexist in the same lesion 1
• Do not overlook non-infectious causes such as Behçet syndrome, fixed drug eruption, or inflammatory bowel disease (Crohn's), which can mimic infectious genital ulceration 1, 2
• In older men, always maintain high suspicion for premalignant or malignant lesions, particularly with atypical presentations or lesions that fail to heal 3, 4
• Screen for diabetes in patients with recurrent candidal balanitis, as 10.9% have undiagnosed diabetes 3