What is the most likely diagnosis for a patient with sharply marginated, smooth, flat-topped, moist anogenital papules and plaques, with a history of multiple sexual partners and illicit drug use?

Diagnosis: Condyloma Lata (Secondary Syphilis)

The most likely diagnosis is condyloma lata (Option A), which represents a highly infectious manifestation of secondary syphilis that presents as smooth, flat-topped, moist papules and plaques in anogenital regions, particularly in patients with high-risk sexual behavior. 1, 2

Clinical Features That Confirm This Diagnosis

The presentation described is pathognomonic for condyloma lata:

• Sharply marginated borders - characteristic of syphilitic lesions 2, 3
• Smooth, flat-topped appearance - distinguishes from verrucous condyloma acuminata 2, 3
• Moist papules and plaques measuring 1-2 cm - typical size and texture for condyloma lata 2, 4
• Anogenital location - the most common site for these lesions 1, 4
• High-risk sexual history - multiple partners significantly increases syphilis risk 1, 2

Why Other Options Are Incorrect

Condyloma acuminata (genital warts) would present differently:

• HPV-induced warts are typically verrucous (cauliflower-like), not smooth and flat-topped 5
• They appear as rough, raised lesions rather than the smooth, moist plaques described 6
• While common in sexually active patients, the morphology doesn't match 5

Basal cell carcinoma is excluded because:

• Occurs primarily in sun-exposed areas, not anogenital regions 2
• Typically presents in older patients (>50 years), not patients in their 30s 2
• Would show pearly borders with telangiectasias, not flat-topped moist papules 2

Lichen simplex chronicus doesn't fit because:

• Results from chronic scratching and presents with lichenification (thickened, leathery skin) 7
• Not associated with multiple sexual partners or high-risk behavior 7
• Lacks the characteristic smooth, moist appearance of condyloma lata 7

Critical Diagnostic Steps

Immediate serologic testing is mandatory:

• Rapid plasma reagin (RPR) or VDRL for screening 8
• Treponema pallidum-specific tests (EIA or TPPA) for confirmation 8
• Expect high titers (often 1:128 or higher) in secondary syphilis 8

Histopathology confirms diagnosis when needed:

• Shows plasma cell-rich dermal infiltrate 3, 4
• Direct visualization of spirochetes using special stains 3, 4
• Verrucous epidermal hyperplasia with innumerable Treponema pallidum organisms 3

Essential Clinical Pearls

Condyloma lata are highly infectious:

• These lesions are filled with spirochetes and represent peak infectivity 1
• Sexual partners within 90 days require evaluation and presumptive treatment 6

Screen for concurrent STIs:

• Test for HIV, as co-infection is common 8
• Screen for gonorrhea and chlamydia given high-risk behavior 1
• Hepatitis B and C testing should be performed 8

Do not confuse with condyloma acuminata:

• The smooth, flat-topped, moist appearance distinguishes condyloma lata from the verrucous appearance of HPV warts 2, 3
• When in doubt, serologic testing for syphilis resolves the diagnostic dilemma 8, 4

Treatment Approach

Standard therapy for secondary syphilis:

• Benzathine penicillin G 2.4 million units intramuscularly as a single dose 2, 8
• Achieves complete resolution within 7-14 days 8
• Follow-up RPR titers at 3,6, and 12 months to confirm serologic cure 8

For penicillin-allergic patients:

• Doxycycline 100 mg orally twice daily for 14 days is an alternative 6
• However, penicillin remains the gold standard 8