The earliest epidemic of syphilis was described in the late 1400s and early 1500s.¹ Syphilis may have been introduced into western Europe in 1493 after Columbus’s initial voyage to the Western Hemisphere.² Syphilitic involvement of the nervous system was first described in the 1800s.³ In 1903, syphilis was first transmitted to experimental animals, and in 1905 Schaudinn and Hoffman discovered Treponema pallidum to be the causative agent.⁴ The Wassermann blood test for syphilis was developed in 1907.⁴ In 1918 Igesheimer wrote a book on syphilis that covered syphilitic ocular disease.⁵ In 1943 the introduction of penicillin revolutionized the treatment of the disease.³ Antibiotics were found in the 1950s to treat syphilis in penicillin-allergic patients.³ In the 1980s there was an increase in the incidence of syphilis associated with the increased incidence of intravenous drug abuse and AIDS.⁶ Although in the 1990s the incidence of new cases of syphilis in the United States declined, syphilis still remained a significant health problem, not only in the United States, but in many developing countries and in Eastern Europe.^7,8,9 Since 2000 there has been an increased incidence of syphilis in the United States and around the world.¹⁰ There are an estimated 12 million new cases of syphilis each year¹¹ with the largest increase in men who have sex with men (MSM) and in noninjecting drug-using women.¹²

Syphilis is an infectious disease caused by the spiral motile flagellated bacteria T. pallidum. The organism is a fastidious, microaerophilic obligate parasite of humans and has not been cultured in vitro.¹³ However, the genome sequence of T. pallidum is available and may provide information about virulence.¹³

Inoculation occurs through the epithelium and is followed by a generalized transient infection (spirochetemia). A primary chancre develops at the inoculation site, generally genital or oral, and regional lymphadenopathy follows. In the secondary stage of syphilis, there is hematogenous spread to local foci in the skin and mucous membranes. During the tertiary stage of syphilis, there is diffuse low-grade inflammation with degeneration and necrosis in the cardiovascular and central nervous systems. Ocular involvement is present in congenital syphilis and may occur in primary, secondary, or tertiary syphilis. In latent syphilis, patients are seroreactive but have no other disease activity.

The incidence of syphilis in the United States, measured by the number of cases reported to the Centers for Disease Control and Prevention (CDC), began to decline during the 1990s but has increased since 2000.¹⁰ Elsewhere in the world, reporting mechanisms are less well established, but the incidence of syphilis still appears to be increasing. With an increased rate of primary and secondary syphilis, there is an increased likelihood of congenital syphilis. Estimates of the number of new cases of congenital syphilis throughout the world range from 700,000 to 1.5 million cases per year.¹⁴ Because syphilitic genital ulceration may increase the transmission of the AIDS virus, there is an increased risk of AIDS associated with an increase in the incidence of syphilis.¹⁵ The severity of syphilis may be increased and the presentation of the disease may be atypical in patients infected with HIV, with an increase in central nervous system involvement.^16,17

Ocular involvement may occur at any stage of syphilis. In congenital syphilis, acute iridocyclitis may be present from birth to age 6 months. Chorioretinitis with the “salt and pepper” fundus, foci of old choroiditis, areas of retinal pigment epithelial hypertrophy, and atrophy may occur at any time after 6 months. Vitreitis may be present. Interstitial keratitis may be present at birth but is more commonly a late manifestation, occurring bilaterally and between ages 5 and 20 years of age.¹⁸

In acquired syphilis, chancre of the conjunctiva or lids may be seen in the primary stage. In secondary syphilis, nonspecific conjunctivitis, scleroconjunctivitis, and syphilids (painless white nodules on the conjunctiva) have all been described.⁵ Iris roseola (Fig. 50.1), early diffuse hyperemia of the iris vasculature, and late localized iris inflammation have been reported.¹⁹ Iritis and iridocyclitis are common. Syphilitic uveitis in tertiary syphilis may occur up to 20 years after the primary infection. Any part of the eye can be affected by syphilis (Table 50.1). Syphilitic eye involvement appears to be more likely in patients with AIDS, but ocular manifestations in these patients may be atypical and more severe.²⁰