Re-evaluation of serological criteria for early syphilis treatment efficacy: progression to neurosyphilis despite therapy. A reply.

Alfredo Rebora, Professor,
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Other Contributors:

July 03, 2012

We read the article of P. Zhou and collaborators1 with great interest. We agree that clinicians should be aware that appropriate therapy in early syphilis may be not sufficient for avoiding late-stage disease, neuro-syphilis in particular. To support such an important issue, we would like to deliver the data we obtained by a retrospective study we conducted some years ago.

The data were collected in our Section of Dermatology by examining the clinical records of 62 patients diagnosed as having syphilis. Thirty of them had early syphilis (either primary/secondary or latent since no more than 2 years) and 32 had latent syphilis for more than 2 years. All had been treated for at least 2 consecutive years with a total of at least 60 million units of benzathine penicillin. All patients were clinically examined at the end of the treatment for neurological lesions and compared with 62 serologically-negative subjects. The control group was of the same gender and age (+3 years). Data have been analysed by the x2 test.

The neurological changes were patellar hyporeflexia (14 cases), myosis (3 cases), anisocoria (3 cases), pupillary light rigidity (3 cases), Romberg sign (1 cases), hypomania (1 case).

Neurological changes were observed in 22 patients (35%) vs 10 (16%) controls. The difference was statistically significant. (x2 = 5.096; p = 0.024). Patients with early syphilis (36%) did not differ from patients with latent syphilis (35%) (x2= 0.029; p=0.865).

Our study, which was conducted at a time in which long penicillin treatments were usual in Italy, shows that penicillin, though extremely effective in clearing the early cutaneous lesions, is grossly inefficient to prevent late complications, neurological in particular. Worst than that, it seems that it may even favour them. In fact, the prevalence of neurological signs in our series is even higher than that found in Oslo study2. This fact may simply depend on the incapacity of penicillin to pass effectively through the hemato-encephalic barrier and achieve treponemicidal concentrations in the central nervous system3, but other factors, either autoimmune or atherosclerotic, should be taken into consideration in the pathogenesis of neuro-syphilis. We believe that a change of the supposedly "adequate" treatment for early syphilis should be endeavoured.

This is retrospective study in which subjects were regular patients with syphilis who have been treated with penicillin many years ago.


1. Zhou P, Gu X, Lu H, Guan Z, Qian Y.Re-evaluation of serological criteria for early syphilis treatment efficacy: progression to neurosyphilis despite therapy. Sex Transm Infect. 2012 Feb 23.

2. Gjestland T. The Oslo study of untreated syphilis; an epidemiologic investigation of the natural course of the syphilitic infection based upon a re-study of the Boeck-Bruusgaard material. Acta Derm Venereol Suppl (Stockh). 1955;35(Suppl 34):3-368

3. Tramont EC. Persistence of Treponema pallidum following penicillin G therapy. JAMA 1976; 236:2206-2207.

Conflict of Interest:

None declared

Conflict of Interest

None declared