Management of Syphilis and Other Sexually Transmitted Diseases

Benjamin Davis

SYPHILIS

In 1943, the dramatic efficacy of penicillin treatment for syphilis was established, and for the next 15 years, the incidence of new cases of syphilis declined steadily to a low of about 6,500 in 1956. The incidence rate of syphilis peaked in 1990 at 20.3 cases per 100,000. Between 1990 and 2000, the incidence of primary and secondary syphilis declined 90% to 2.1 cases per 100,000, which remains the lowest incidence rate since national reporting began in 1941. Between 2000 and 2002, the incidence of syphilis continued to fall for women but rose in men and, in particular, among men who have sex with men (MSM). The proportion of cases of syphilis attributed to MSM increased from 7% in 2000 to 64% in 2004. Between 1999 and 2003, a well-described outbreak of syphilis among MSM in San Francisco was linked to Internet use for finding sexual partners, introducing a novel risk factor for sexually transmitted disease (STD) transmission, as well as an effective means for departments of public health to notify sexual contacts and prevent new cases. Syphilis continues disproportionately to affect non-Hispanic Blacks at rates eightfold higher than for non-Hispanic Whites, although these rates are continuing to decline.

Pathophysiology, Clinical Presentation, and Course (1, 2, 3, 4, 5 and 6)

Humans are the only natural reservoir of Treponema pallidum. Except for cases of transplacental transmission, virtually all cases are acquired by sexual contact with persons having active infectious lesions. T. pallidum readily penetrates abraded skin and intact mucous membranes to multiply locally and disseminate through the lymphatics and bloodstream. Circumcision does not reduce the risk for syphilis.

The course of syphilis can be divided into primary, secondary, latent, and tertiary phases.

Primary Syphilis

The lesion of primary syphilis is the chancre, which occurs at the site of inoculation about 3 weeks after exposure. The chancre is usually located on the genitalia, but it can occur in the anal canal, on oral mucosa, on the hands, or in other locations. The lesion begins as a small papule that enlarges and undergoes superficial necrosis to produce an ulcer with a clean base and sharp margins. The chancre is typically painless, and patients
are free of constitutional symptoms, although regional nodes may be enlarged. The chancre is teeming with spirochetes and is highly infectious. Even without therapy, the chancre heals completely in 2 to 6 weeks.

Secondary Syphilis

About 2 months after the primary infection, the features of secondary syphilis may appear. Secondary syphilis is a systemic disease. A flulike syndrome is common, as is generalized lymphadenopathy. The most characteristic feature of secondary syphilis is a generalized skin eruption. Lesions may be macular, papular, or papulosquamous but tend to be symmetric and uniform in size; typically, the palms and soles are involved. Patches and split papules often occur on the mucous membranes. Secondary syphilis can involve many other organs; clinical manifestations may include aseptic meningitis, hepatitis, nephritis, or uveitis. Patients with secondary syphilis are contagious. As in primary syphilis, the manifestations of secondary syphilis resolve spontaneously even without therapy, although up to 25% of patients exhibit a brief relapse of secondary lesions.

Latent and Tertiary Syphilis

Untreated patients without active lesions are considered to have latent syphilis. About two thirds of these patients remain entirely asymptomatic, but in the remaining one third, the lesions of tertiary syphilis develop, usually 10 to 40 years after primary infection. The major forms of tertiary syphilis include (a) cardiovascular syphilis, which is characterized by aneurysmal dilation of the ascending aorta and aortic insufficiency; (b) neurosyphilis, which may present as general paresis, with disorders of intellect and personality, or as tabes dorsalis, with ataxic gait, impaired pain and temperature sensation, autonomic dysfunction, and hypoactive reflexes; and (c) gummatous syphilis, which is represented by slowly progressive, destructive granulomatous lesions of skin, bone, liver, or other organs.

Natural history studies from Oslo, Norway, and Tuskegee, Alabama indicate that clinically manifest tertiary syphilis develops in approximately one third of patients with untreated syphilis and that evidence of cardiovascular syphilis can be found in more than one half at autopsy. In the retrospective Oslo study, 10% of patients had clinically evident cardiovascular syphilis, 7% had neurosyphilis, and 16% had gummatous disease. The incidence of cardiovascular syphilis was higher and that of neurosyphilis was lower in the prospective (and unethical) Tuskegee study.

Infection of the Central Nervous System

Infection of the central nervous system may occur at any point in the natural history of untreated syphilis and may be more likely in HIV-positive patients. Even in the absence of neurologic symptoms, about 25% of patients with primary, secondary, or latent infection have cerebrospinal fluid (CSF) abnormalities (pleocytosis, elevated protein, positive Venereal Disease Research Laboratory [VDRL] test). Although it is not clear how many of these patients will ultimately be affected by symptomatic neurosyphilis, concern is warranted. Organisms have been detected from the central nervous system in 30% of patients with untreated primary and secondary disease.

Syphilis and HIV Disease

Patients with syphilis are at increased risk for other STDs, including HIV infection. Moreover, patients with HIV infection are at increased risk for syphilis. Some studies find that HIV-infected patients have unusually high titers in their syphilis serology, whereas others find that seroconversion can be delayed or blunted by concomitant HIV infection, particularly in patients with symptomatic AIDS. In addition to being more common in HIV-infected persons, syphilis in these patients may be clinically atypical, unusually severe, or more difficult to treat successfully. Central nervous system syphilis may also be more likely in HIV-positive patients.

Congenital Syphilis

Congenital syphilis occurs as a result of transplacental transmission of spirochetes during the second or third trimester of pregnancy. Fetal loss is about 60%. Half of surviving infants have stigmata such as nonimmune hydrops, hepatosplenomegaly, rhinitis, and skin rash. Serious permanent consequences may develop in the absence of therapy. Congenital syphilis can be prevented by prompt treatment of maternal infection, and testing for syphilis is mandatory for all pregnant women, with or without symptoms.

Diagnosis (7)

The diagnosis usually depends on clinical features and serologic testing.

Serologic Testing

The most widely used serologic tests for syphilis employ a nontreponemal antigen (lipoidal extract of mammalian tissues). Examples include the VDRL, Hinton, and rapid plasma reagin (RPR) tests. These are excellent screening tests, but the falsepositive rate is as high as 30%, often as the result of unrelated infections or inflammatory diseases that produce hyperglobulinemia. More-specific serologic tests use treponemal antigens and can distinguish true-positive from false-positive results. The most frequently used treponemal tests are the microhemagglutination-T. pallidum test and the fluorescent treponemal antibody absorption test. Because of increased sensitivity, newer treponemaspecific assays (EIA) are now recommended for screening purposes, with positive results being followed by a nontreponemal test such as an RPR (see Chapter 124).

The diagnosis of neurosyphilis may be difficult to establish conclusively. A positive CSF-VDRL is very specific but insensitive for neurosyphilis. Often, the diagnosis is made by a combination of CSF abnormalities (>5 white blood cells/mm³, elevated protein) with or without clinical symptoms (uveitis, hearing loss, posterior column spinal cord dysfunction) and a positive serum serology.

Some patients with primary syphilis manifest false-negative nontreponemal and treponemal test results. False negatives are most likely to occur in patients with infections of less than 30 days’ duration. In most patients with HIV, serologic tests for syphilis are accurate and reliable for diagnosis, but in some, atypically high, low, or fluctuating titers may be encountered. It is recommended that when serologic tests do not correspond with clinical findings suggestive of early syphilis, other tests should be considered.

Dark-Field Examination

For persons with a suspect primary lesion and nondiagnostic serologic findings, a dark-field examination should be performed and serologic studies repeated in 10 to 14 days. T. pallidum cannot be cultured in vitro, but the diagnosis of syphilis can be made by direct visualization of treponemes from the chancre. This is a specialized technique that requires darkfield or fluorescent microscopy and very experienced observers. The Warthin-Starry stain can be used to visualize organisms in biopsy specimens.

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