Last reviewed: 25 May 2021
Last updated: 29 May 2019



History and exam

Key diagnostic factors

  • anogenital ulcer
  • lymphadenopathy
  • diffuse rash
  • constitutional symptoms
  • fatigue
  • rhinitis (congenital syphilis)
  • hepatosplenomegaly (congenital syphilis)
  • patchy alopecia
  • condylomata lata
  • memory impairment, altered mood, confusion, or dementia
  • visual disturbance
  • Argyll-Robertson pupils
  • loss of sense of vibration, proprioception, and position sense
  • ataxia
  • loss of anal and bladder sphincter control
  • positive Romberg sign
  • diastolic murmur
  • rubbery lesions/nodules with a necrotic center
  • miscarriage, stillbirth, or neonatal death (congenital syphilis)
  • premature labor and intrauterine growth retardation (congenital syphilis)
  • neonatal skin rash (congenital syphilis)
  • tibial bowing (congenital syphilis)
  • craniofacial malformation (congenital syphilis)
  • tooth abnormalities (congenital syphilis)
  • necrotizing funisitis (congenital syphilis)

Other diagnostic factors

  • mouth ulcer
  • asymptomatic with positive serology (latent syphilis)
  • tremor
  • headache
  • meningismus
  • eye pain
  • hearing loss
  • seizures
  • peripheral edema
  • jaundice
  • peripheral neuropathy
  • areflexia
  • angina
  • dyspnea
  • organomegaly
  • skin or visceral organ perforation or collapse of structure
  • neonatal neurologic abnormalities (congenital syphilis)

Risk factors

  • sexual contact with an infected person
  • men who have sex with men (MSM)
  • illicit drug use
  • commercial sex workers
  • multiple sexual partners
  • people with HIV or other STIs
  • syphilis during pregnancy (risk for congenital syphilis)

Diagnostic investigations

1st investigations to order

  • dark-field microscopy of swab from lesion
  • serum treponemal enzyme immunoassay (EIA)
  • serum Treponema pallidum particle agglutination (TPPA)
  • serum Treponema pallidum hemagglutination (TPHA)
  • serum fluorescent treponemal antibody absorption¬†(FTA-ABS) test
  • immunocapture assay
  • line immunoassay (LIA) serologic test
  • serum rapid plasma reagin (RPR) test
  • serum Venereal Disease Research Laboratory (VDRL) test

Investigations to consider

  • lumbar puncture, cerebrospinal fluid (CSF) analysis
  • chest x-ray
  • echocardiogram
  • CT brain
  • MRI brain
  • HIV test
  • fetal ultrasound scan
  • CBC
  • cranial ultrasound
  • long-bone x-rays
  • liver function tests
  • evoked auditory potentials
  • audiometry

Emerging tests

  • Treponema pallidum polymerase chain reaction (PCR) (sample taken directly from ulcerative lesions)
  • point of care (POC) testing with either treponemal or combination treponemal/nontreponemal antibody

Treatment algorithm


Professor and Chair

Department of Pediatrics

University of Connecticut School of Medicine




JCS is the author of references cited in this topic.

Associate Professor of Pediatrics

Adjunct Associate Professor of Pharmacy

Department of Pediatrics

University of Connecticut School of Medicine




NB declares that he has no competing interests.

Research Associate





AC declares that she has no conflicting interests.

Dr Juan C. Salazar, Dr Nicholas Bennett, and Dr Adriana Cruz would like to gratefully acknowledge Patrick French and Nooshin Barmania, previous contributors to this topic. PF is an author of a reference cited in this topic. NB declares that she has no competing interests.

Peer reviewersVIEW ALL

Associate Professor of Medicine

University of Southern California

Keck School of Medicine

Los Angeles



RAL declares that he has no competing interests.

Assistant Professor of Medicine

Harvard Medical School

Director of Research

Global Health Delivery Project

Harvard School of Public Health




WR declares that he has no competing interests.

Consultant Paediatrician

Croydon University Hospital




JH declares that she has no competing interests.

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