Clinical and Imaging Features of Syphilis from Head to Toe

Syphilis, a bacterial infection caused by Treponema pallidum, is resurging globally. It is classified as acquired or congenital syphilis. Acquired syphilis progresses through primary, secondary, and tertiary stages. Pathologically, acquired syphilis is characterized by vasculopathy, perivascular infiltrates in syphilitic lesions, and reactive lymphadenopathy. Primary and secondary syphilis frequently manifest with cutaneous and mucosal lesions accompanied by extensive lymphadenopathy at the initial sites of sexual contact, such as the genitalia, oropharynx, and anorectum. These manifestations may mimic malignancies. Tertiary syphilis encompasses cardiovascular syphilis, late neurosyphilis, and gummas, each manifesting distinct imaging characteristics. Most acquired cases are suspected on the basis of dermatologic signs and patient history and are confirmed serologically. Imaging findings alone may not be diagnostic and can overlap with those of other infectious, inflammatory, or neoplastic conditions, necessitating clinical correlation and laboratory testing. However, in patients with atypical clinical presentations, imaging has an important role in providing valuable diagnostic clues and guiding appropriate clinical treatment. The incidence of congenital syphilis is also increasing in parallel with the overall increase in syphilis infections. A comprehensive understanding of the diverse imaging manifestations in multiple organ systems is vital for radiologists to accurately diagnose and guide appropriate management in the era of resurgent syphilis. The authors provide an overview of acquired and congenital syphilis, detailing the epidemiologic and pathophysiologic characteristics, diagnostic approaches, clinical courses, and imaging features. ^©RSNA, 2025 Supplemental material is available for this article.