Last reviewed: March 2019
Last updated: May  2018



History and exam

Key diagnostic factors

  • genital 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 nodules with a necrotic center
  • miscarriage or stillbirth (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 (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
  • illicit drug use
  • commercial sex workers
  • multiple sexual partners
  • people with HIV or other STDs
  • syphilis during pregnancy (risk for congenital syphilis)

Diagnostic investigations

1st investigations to order

  • dark-field microscopy of swab from lesion
  • serum treponemal enzyme immune assay (EIA)
  • serum T pallidum particle agglutination (TPPA)
  • serum T pallidum hemagglutination (TPHA)
  • serum fluorescent antibody absorption (FTA-ABS) tests
  • immunocapture assay (ICA)
  • INNO-LIA test
  • serum rapid plasma reagin (RPR) test
  • serum Venereal Disease Research Laboratory (VDRL) test
  • serum cardiolipin-based test
Full details

Investigations to consider

  • lumbar puncture, CSF analysis
  • CXR
  • echocardiogram
  • CT brain
  • MRI brain
  • HIV test
  • fetal ultrasound scan
  • CBC
  • cranial ultrasound
  • long-bone x-rays
  • LFTs
  • evoked auditory potentials
  • audiometry
Full details

Emerging tests

  • point of care (POC) testing with either treponemal or combination treponemal/nontreponemal antibody
  • T pallidum PCR (sample taken directly from ulcerative lesions)
Full details

Treatment algorithm


Authors VIEW ALL

Professor and Chair

Department of Pediatrics

University of Connecticut School of Medicine




JCS is the author of references cited in this monograph.

Assistant Professor of Pediatrics

Adjunct Assistant 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 monograph. PF is an author of a reference cited in this monograph. NB declares that she has no competing interests.

Peer reviewers VIEW 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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