Clinical Pearls & Morning Reports

By Carla Rothaus

Published February 26, 2020


When is routine CSF examination recommended in patients with syphilis? 

Today, the incidence of syphilis in the United States has returned to levels not seen in more than 20 years. Read the NEJM Review Article here.

Clinical Pearls

Q: Describe the current epidemiology of syphilis in the United States.

A: Since 2000, the increase in rates of primary and secondary syphilis in the United States has been largely attributable to an increase in rates among men by a factor of more than 3; in 2018, men accounted for 86% of all patients with syphilis. More than half of men with incident syphilis reported having sex with men, and 42% of those men were infected with the human immunodeficiency virus (HIV). A second, more recent epidemic in the United States is affecting heterosexual men and women. Rates of primary and secondary syphilis among women more than doubled between 2014 and 2018. The remarkable increase in the number of cases of primary and secondary syphilis among women of childbearing age is mirrored by increasing numbers of congenital syphilis cases and increasing infant mortality.

Q: What clinical features of syphilis may manifest at any stage of the disease?

A: Asymptomatic or symptomatic neurologic involvement may occur during any stage of syphilis. Central nervous system (CNS) invasion by treponemes is accompanied by abnormal cerebrospinal fluid (CSF) findings in up to 50% of persons after early infection, even in the absence of clinical features (termed asymptomatic neurosyphilis). Ocular syphilis and otic syphilis are, technically, distinct entities from neurosyphilis but may occur concomitantly. Like neurosyphilis, they can occur during any stage of infection.

Morning Report Questions

Q: When is routine CSF examination recommended in patients with syphilis?

A: The CDC does not recommend routine CSF examination for persons with early syphilis, irrespective of HIV status, unless neurologic signs are present. A CSF examination is necessary in all patients with neurologic signs or symptoms and in neurologically asymptomatic patients with evidence of tertiary syphilis. A CSF examination is not necessary to diagnose ocular or otic syphilis in patients with reactive serologic tests because up to 30% of patients with ocular syphilis and up to 90% of patients with otic syphilis have a normal CSF examination. Although serologic testing for syphilis in elderly patients undergoing an evaluation for dementia is not routinely recommended in most clinical settings, such testing is frequently performed. Consequently, patients may be found to have reactive serologic tests (a reactive treponemal test accompanied by either a reactive or a nonreactive nontreponemal test). Information about a history of syphilis, treatment, and nontreponemal titers may be valuable but is rarely available. Before CSF testing is performed, clinicians should estimate the probability of syphilis, as opposed to another diagnosis, as a cause of the observed neurologic findings. If the pretest probability is moderate or high, a CSF examination is warranted.

Q: What is the drug of choice for syphilis?

A: Penicillin is highly effective for all stages of syphilis and is the drug of choice. Resistance to penicillin has not been observed in Treponema pallidum. Recent shortages of penicillin G benzathine underscore the importance of establishing alternative treatment regimens, particularly in pregnant women. For persons with a documented penicillin allergy, desensitization and treatment with penicillin are recommended. Limited data preclude the use of alternative antibiotics agents, which should be considered only when treatment with penicillin is not possible or is absolutely contraindicated. Ceftriaxone has been shown to have efficacy similar to that of penicillin in all stages of syphilis, although the data are restricted to observational studies. Ceftriaxone penetrates the CNS well and is an option for treating neurosyphilis in nonpregnant adults with penicillin allergy in whom desensitization is not possible.

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