Origins of syphilis and management in the immunocompetent patient: Facts and controversies

Abstract

Despite the continued efficacy of penicillin since the 1940s, many aspects of the natural history, diagnosis, and management of syphilis remain controversial. A key factor among the numerous factors explaining the persistence of significant areas of controversies is the absence of a gold standard direct method for distinguishing between the different stages of syphilis and appraising treatment response. This contribution presents an overview of some of the most debated aspects of the origins, diagnosis, and management of syphilis in immunocompetent patients. The two main current hypotheses on the origins of Treponema pallidum are the “Columbian” and the “Pre-Columbian” hypotheses. Strong evidence supports that Columbus' crew brought T pallidum to Europe at the time of discovery of the New World. Because T pallidum culture and inoculation to animals are not readily available methods, the gold standard method for the diagnosis of syphilis is the direct identification of T pallidum by dark field microscopy or direct fluorescent antibody tests. These methods, however, are inapplicable in many patients, and thus the diagnosis of syphilis is usually based on the clinical and serologic picture. Serologic tests should only be considered as surrogate markers of the disease and do not provide definite distinction between syphilis stages. The optimal combination of serologic tests is still undefined. Other areas of controversy include the identification of patients who would benefit from a lumbar puncture, the diagnostic criteria of neurosyphilis, and the most relevant markers of treatment response.

Introduction

In most cases of syphilis, the diagnosis is straightforward, and the standard treatment with penicillin is cheap, convenient, well tolerated, and efficient; nevertheless, many aspects of the natural history, the diagnosis, and the management remain controversial. Why is a disease whose first epidemic was recorded in 1495,1, 2 and for which an efficient treatment has been available since the early 1940s, still a matter of controversy? Several factors could be discussed:

• The culture of Treponema pallidum (TP), the causative agent is complex, which hampers the laboratory production of treponemal strains and thus the study of the pathophysiology of the disease and the recognition of a gold standard for monitoring treatment efficacy³; hence, treatment response in current practice can be defined clinically and/or serologically but not microbiologically. It is also difficult to distinguish relapse from reinfection.⁴

• The diagnostic criteria for the different stages of the disease are not consensual, which creates difficulties when comparing data across studies.

• The relatively low incidence of syphilis in industrialized countries impedes the recruitment of large samples in clinical trials.

• The often high rate of loss to follow-up associated with syphilis in current practice and in clinical trials4, 5 makes it difficult to properly appraise long-term efficacy.

• The low cost of the main therapeutic group of drugs—namely, the different derivatives of penicillin—refrains the potential willingness of pharmaceutical companies to support syphilis clinical research.

This contribution presents an overview of some of the most debated aspects of the origins, diagnosis, and management of syphilis in immunocompetent patients. The controversial issues of the management of syphilis in HIV-infected patients are discussed elsewhere in this issue of Clinics in Dermatology.