What are the symptoms and treatment options for syphilis?

Symptoms of Syphilis

Primary Syphilis

Primary syphilis presents with a painless ulcer (chancre) at the site of infection, typically accompanied by regional lymphadenopathy. 1

• The chancre is characteristically painless and indurated at the contact site where T. pallidum entered the body 2
• An indolent regional lymph node swelling is usually associated with the primary chancre 2
• In HIV-infected individuals, multiple or atypical chancres may occur, and primary lesions might be absent or missed 1
• The primary chancre heals spontaneously after several weeks, even without treatment 2

Secondary Syphilis

Secondary syphilis develops weeks after the primary lesion resolves and can mimic acute HIV infection with constitutional symptoms. 1

• Constitutional symptoms include fever and malaise due to T. pallidum bacteremia 2
• Generalized lymphadenopathy is a prominent feature 2
• Non-pruritic rash that is diffuse and often involves the palms and soles 1, 2
• Mucocutaneous lesions including condylomata lata (genital or perineal lesions) 2, 3
• Mucous patches in the oral cavity, presenting as a specific angina 2
• Secondary syphilis can have CSF abnormalities even without neurologic symptoms 1
• Symptoms resolve spontaneously after several relapses of decreasing intensity 2

Latent Syphilis

Latent syphilis is characterized by positive serologic tests without any clinical manifestations. 1

• Early latent syphilis occurs within the first year after infection 1
• Late latent syphilis is diagnosed more than one year after infection 1
• Patients are asymptomatic but remain serologically positive 1

Tertiary Syphilis

Tertiary syphilis occurs in approximately 25% of untreated patients after 3-12 years of latency, while 75% experience spontaneous healing. 1, 2

• Gummatous lesions: superficial nodular syphilids and gummas (granulomatous skin reactions) 1, 2
• Cardiovascular syphilis: involvement of the cardiovascular system 1, 2
• Neurologic involvement: can include meningitis, uveitis, hearing loss, or stroke 4
• Bone involvement may also occur 2

Neurosyphilis

Neurosyphilis can occur at any stage of syphilis and requires specific recognition. 4

• Cognitive dysfunction 1
• Motor or sensory deficits 1
• Ophthalmic symptoms including uveitis, neuroretinitis, and optic neuritis 1
• Auditory symptoms including hearing loss 1, 4
• Cranial nerve palsies 1
• Symptoms or signs of meningitis 1
• Late manifestations (metasyphilis) include tabes dorsalis and progressive paralysis, occurring 10-30 years after primary infection 2

Congenital Syphilis

In pregnancy, up to 40% of fetuses with in-utero exposure to syphilis are stillborn or die from their infection during infancy. 4

Treatment Overview

The recommended treatment for early syphilis (primary, secondary, and early latent) is benzathine penicillin G 2.4 million units IM as a single dose. 1, 4

• Late latent syphilis or latent syphilis of unknown duration requires benzathine penicillin G 7.2 million units total, administered as three doses of 2.4 million units IM at 1-week intervals 1
• Neurosyphilis requires aqueous crystalline penicillin G 18-24 million units per day IV for 10-14 days 1
• For penicillin-allergic patients with early syphilis, doxycycline 100 mg orally twice daily for 14 days is an alternative 1, 5
• For penicillin-allergic patients with late syphilis, doxycycline 100 mg orally twice daily for 28 days 6, 5
• Pregnant women and patients with neurosyphilis who are penicillin-allergic must be desensitized and treated with penicillin, as it is the only effective option 6

Important Clinical Considerations

• All patients with syphilis should be tested for HIV 1
• The Jarisch-Herxheimer reaction (acute febrile reaction with headache and myalgia) may occur within 24 hours after any therapy for syphilis 6
• Sexual transmission occurs only when mucocutaneous lesions are present, which are uncommon after the first year of infection 6