What is the most likely cause of red-brown macular lesions on the palms and soles in a person with psoriasis secondary to syphilis, atypical psoriasis, or dermatitis?

Most Likely Diagnosis: Secondary Syphilis

In a person with psoriasis presenting with red-brown macular lesions on palms and soles, secondary syphilis is the most likely diagnosis and must be ruled out immediately with serologic testing. 1, 2

Critical Diagnostic Reasoning

Why Secondary Syphilis is Most Likely

• Red-brown macules on palms and soles are the hallmark presentation of secondary syphilis, with symmetric palmoplantar involvement being highly characteristic 1, 3
• The American Academy of Dermatology emphasizes that acute onset over weeks is inconsistent with psoriasis, which follows a chronic, stable course or gradual progression 1, 2
• Palmoplantar psoriasis presents with hyperkeratotic, fissured plaques, NOT red-brown macules 2
• The CDC guidelines highlight that copper-colored macules with symmetric distribution strongly favor syphilis over other dermatoses 2

Why Other Diagnoses are Less Likely

• Atypical psoriasis: While psoriasiform syphilis exists and can mimic psoriasis 4, 5, true palmoplantar psoriasis lacks the red-brown macular morphology and acute onset pattern 2
• Dermatitis: Atopic or seborrheic dermatitis do not characteristically involve palms and soles with this specific morphology 2
• The presence of pre-existing psoriasis does not exclude secondary syphilis; in fact, syphilis is known as "the great masquerader" and can coexist with or mimic other conditions 4

Immediate Diagnostic Workup

The American Academy of Dermatology recommends immediate serologic testing for syphilis in any patient with symmetric palmoplantar red-brown macules 1:

• RPR/VDRL (non-treponemal test) 1, 2
• Treponemal-specific testing (FTA-ABS or TP-PA) to confirm diagnosis 2
• HIV screening is mandatory, as syphilis and HIV frequently coexist 1, 2

Treatment Implications

If syphilis is confirmed, benzathine penicillin G 2.4 million units IM as a single dose is the standard treatment for secondary syphilis per CDC guidelines 1:

• Partner notification and treatment is mandatory 1, 2
• Follow-up serology is required to confirm treatment response 1
• Avoid treating presumptively as psoriasis with immunosuppressive agents before excluding syphilis 4

Critical Clinical Pitfalls

• Never initiate immunosuppressive therapy for presumed psoriasis without first excluding syphilis in patients with palmoplantar involvement 4, 5
• The coexistence of known psoriasis does not rule out secondary syphilis; both conditions can occur simultaneously 4
• Dermoscopy can help differentiate palmar syphiloderm from palmar papular psoriasis when clinical distinction is difficult 6
• Histopathology may show psoriasiform features in secondary syphilis, making clinical correlation essential 4, 5