He who knows syphilis knows medicine.
Sir William Osler
Syphilis, caused by the bacterium Treponema pallidum, is spread by either sexual contact or transmission from a pregnant woman to her fetus. The course of the disease is divided into 4 stages: primary, secondary, latent, and tertiary (late). Initial inoculation occurs through intact mucous membranes or abraded skin and, within 6 weeks, results in a small ulcerated, painless papule called a chancre. The spirochetes readily enter the lymphatic system and bloodstream. The chancre heals spontaneously, and signs of dissemination appear after a variable quiescent period of several weeks to months.
The secondary stage is heralded by a truncal rash that may spread over the entire body. Fever, malaise, adenopathy, and hair loss may occur. Meningitis, uveitis, optic neuritis, and hepatitis may also occur, but are less common. The secondary lesions may resolve in a few weeks or may relapse in the first year. Without treatment, the disease enters the latent stage.
Latent syphilis, which is characterized by positive serologic test results in a patient without clinical signs, is divided into 2 stages. The early latent stage occurs within 1 year of infection. During this time, the disease is potentially transmissible, because relapses associated with spirochetemia are possible. The late latent stage is associated with immunity to relapse and resistance to infectious lesions.
Tertiary manifestations can occur many years after the initial untreated infection. Up to one-third of untreated cases of latent disease progress to this stage; the remaining two-thirds either are subclinical or resolve spontaneously. Tertiary disease is characterized by destructive granulomatous lesions with a typical endarteritis that can affect the skin, bones, joints, oral and nasal cavities, parenchymal organs, cardiovascular system, eyes, meninges, and central nervous system (CNS).
On pathologic examination, obliterative endarteritis with a perivascular infiltrate of lymphocytes, monocytes, and plasma cells is a feature of all active stages of syphilis. Gummata are a form of granuloma that can develop on the skin, bones, or other organs during tertiary syphilis.
Ocular syphilis and neurosyphilis can occur at any stage of syphilis. Ocular syphilis manifests most commonly as posterior uveitis or panuveitis, but it can also present with interstitial keratitis, anterior uveitis, optic neuropathy, and retinal vasculitis.
Most cases of syphilis are diagnosed serologically. Nontreponemal tests such as the VDRL test or rapid plasma reagin (RPR) test are usually positive during the early stages of the disease, uniformly positive during the secondary stage, and progressively nonreactive in the later stages. Nontreponemal test results become predictably negative after successful therapy and can be used to assess the efficacy of treatment; however, in patients with a variety of autoimmune diseases, false-positive results can occur, especially in patients with systemic lupus erythematosus and antiphospholipid syndrome (see Chapter 9 in this volume).
Treponemal tests include the fluorescent treponemal antibody absorption (FTA-ABS) test, the hemagglutination treponemal test for syphilis (HATTS), the T pallidum hemagglutination assay (TPHA), and the microhemagglutination test for T pallidum (MHA-TP). Treponemal antibody detection tests are more specific than nontreponemal tests, and should be considered confirmatory, especially in cases in the later stages of disease. False-positive results of treponemal tests can occur in 15% of patients with systemic lupus erythematosus, in patients with other treponemal infections or Lyme disease, and, in rare instances, in patients who have lymphosarcoma or who are pregnant.
The ELISA, Western blot, and DNA PCR techniques may allow more rapid and accurate diagnosis of congenital syphilis and neurosyphilis.
Excerpted from BCSC 2020-2021 series: Section 1 - Update on General Medicine. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.