Syphilis

GENERAL PRINCIPLES

• Syphilis is caused by the spirochete Treponema pallidum.

• There is a high rate of HIV coinfection in patients with syphilis, from 40% to 70%, and HIV infection should be excluded with appropriate testing.²

• Syphilis can have an atypical course in HIV-infected patients; treatment failures and progression to neurosyphilis are more frequent in this population.

• Syphilis rates in the United States are increasing since the year 2000, especially among MSM.

DIAGNOSIS

Clinical Presentation

• Primary syphilis develops within several weeks of exposure and manifests as one or more painless, indurated, superficial ulcerations (chancre).

• Secondary syphilis develops 2-10 weeks after the chancre resolves and may produce a rash (usually involves palms and soles), mucocutaneous lesions, adenopathy, and constitutional symptoms.

• Tertiary syphilis follows between 1 and 20 years after infection and includes cardiovascular and gummatous disease.

• Neurologic syphilis (general paresis, tabes dorsalis, meningovascular, ocular, or otologic syphilis) is usually a late manifestation, but can occur earlier. Ocular syphilis can occur with any stage of syphilis, is increasingly common, and can lead to blindness. Eye manifestations of syphilis include uveitis and retinitis. All patients with syphilis should be evaluated for eye complaints as well as neurological complaints. Otosyphilis is also increasing in prevalence.³

• Congenital syphilis occurs by vertical transmission from infected mothers and results in stillbirth in up to 40% of pregnancies and has increased by 279% from 2015 to 2019.⁴ Infected neonates may develop fetal hydrops, rash, hepatomegaly, myocarditis, neurologic disease, and other varied presentations.

Diagnostic Testing

• In primary syphilis, dark-field microscopy of lesion exudates, when available, may reveal spirochetes.

• Reverse sequence testing (measuring an enzyme-linked immunosorbent assay or multiplex flow immunoassay before a quantitative RPR) is used by some jurisdictions and may detect early primary syphilis that may otherwise be missed with traditional screening.

• Diagnosis of secondary syphilis is made on the basis of positive serologic studies and the presence of a compatible clinical illness.

• Syphilis, early nonprimary, nonsecondary is a serologic diagnosis in the absence of symptoms when the patient has been serologically positive for lt;1 year.

• Syphilis of unknown duration or latent syphilis is a serologic diagnosis in the absence of symptoms when the patient has been serologically positive for gt;1 year or for unknown duration.

• To exclude neurosyphilis, a lumbar puncture (LP) should be performed in all patients with neurologic symptoms. For patients with ophthalmic or otosyphilis, LP is indicated if they also have other neurological signs or symptoms. Additionally, some experts recommend LP in patients living with HIV (PLWH) with evidence of tertiary disease, treatment failure, or late syphilis; however, treatment based on abnormal LP findings in the absence of signs or symptoms of neurosyphilis in PLWH and clinical outcomes are not improved.⁵ VDRL should be performed on cerebrospinal fluid (CSF), although sensitivity is low and a negative VDRL does not rule out neurosyphilis.

• Response to treatment should be monitored with nontreponemal serologic tests at 3, 6, and 12 months after treatment. In patients with HIV, tests should be checked every 3 months after treatment for 1 year. Inadequate treatment response after treatment is defined as a lack of fourfold decline in RPR titer at 12 months after primary, secondary or early latent syphilis, or at 24 months after late latent or syphilis of unknown duration.

• For neurosyphilis, no need for repeat CSF exam at 6 months if adequate RPR response and no neurological signs or symptoms are present.