Signs and Symptoms of Secondary Syphilis
Secondary syphilis is characterized by localized or diffuse mucocutaneous lesions with generalized lymphadenopathy, typically occurring 2-8 weeks after the primary chancre, which may still be present. 1
Cutaneous Manifestations
Classic Rash Pattern
- The hallmark is a maculopapular rash that characteristically involves the palms and soles—a pathognomonic feature distinguishing it from most other rashes. 2
- The rash begins on the trunk and spreads peripherally to involve the extremities, progressing from small, blanching, pink macules to maculopapular lesions, sometimes with central petechiae. 2
- The rash typically spares the face and is non-pruritic. 3
- Lesions may present as macular, maculopapular, papulosquamous, or pustular eruptions. 1, 2
Additional Skin Findings
- Condyloma lata: moist, flat, raised fleshy papular lesions that develop in warm intertriginous regions (groin, axillae, perianal area). 2, 4
- Mucous patches may appear in the oral cavity, presenting as a specific angina with white or gray erosions. 3
Important Clinical Pitfall
- Absence of rash does not exclude secondary syphilis—less than 50% of patients have a rash in the first 3 days, and skin pigmentation can obscure the rash in patients with darker skin tones. 2
- Palmoplantar involvement may be absent in rare granulomatous variants of secondary syphilis. 5
Systemic Manifestations
Constitutional Symptoms
- Fever and malaise are common presenting features. 2, 4
- Anorexia, arthralgias, and headache frequently accompany the rash. 2
- These systemic symptoms can persist from days to several weeks before resolving. 2
Lymphadenopathy
- Generalized lymphadenopathy accompanies the rash in most cases and is a key diagnostic feature. 1, 2
- Regional lymph node swelling is typically indolent and non-tender. 3
Organ System Involvement
Hepatic Involvement
- Secondary syphilis can involve virtually all organ systems, including the liver, manifesting as syphilitic hepatitis with elevated liver enzymes. 6
Central Nervous System
- Invasion of CSF by T. pallidum with accompanying CSF abnormalities is common in secondary syphilis, though most patients do not develop clinical neurosyphilis after appropriate treatment. 1
- Secondary syphilis can mimic acute primary HIV infection with constitutional symptoms and CSF abnormalities. 7
Special Considerations in HIV Co-infection
HIV co-infection significantly alters the presentation of secondary syphilis and should always be considered. 2
- More apparent and severe clinical lesions with accelerated disease progression. 2, 8
- Atypical presentations including rapidly progressive papulopustular lesions. 2
- Unusual manifestations such as generalized hyperpigmented dermatosis that may mimic other HIV-associated conditions like Kaposi's sarcoma. 8
- All patients with syphilis should be tested for HIV. 7
Temporal Relationship to Primary Infection
- Secondary syphilis typically develops 2-8 weeks after the primary chancre appears. 2, 5
- The primary chancre may still be present when secondary symptoms emerge. 1
- Without treatment, secondary syphilis resolves spontaneously after several relapses of decreasing intensity, followed by latent syphilis. 3
Diagnostic Confirmation
Clinical recognition alone is insufficient—diagnosis requires both characteristic clinical findings and serologic confirmation. 2