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Original research
Clinical and laboratory features of 244 men with primary syphilis: a 5-year single-centre retrospective study
  1. Stefano Ramoni1,
  2. Giovanni Genovese1,2,
  3. Andrea Pastena1,
  4. Giovanni Casazza3,
  5. Giovanna Lunghi4,
  6. Angelo Valerio Marzano1,2,
  7. Marco Cusini1
  1. 1 Dermatology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
  2. 2 Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
  3. 3 Department of Biomedical and Clinical Sciences "L. Sacco", Universita' degli Studi di Milano, Milan, Italy
  4. 4 Microbiology and Virology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore di Milano Policlinico, Milan, Italy
  1. Correspondence to Dr Marco Cusini, Dermatology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Pace, 9 - 20122 Milan, Italy; marco.cusini{at}


Background Syphilis incidence has exponentially increased in recent decades, particularly among men who have sex with men (MSM). Primary syphilis is characterised by a chancre appearing at the site of Treponema pallidum (TP) inoculation. Atypical morphological variants of syphilitic chancre are frequent. Clinical suspicion must be confirmed either by the demonstration of TP within the lesion through direct tests, such as dark field microscopy (DFM) or T. pallidum nucleic acid amplification technique (TP-NAAT), or by serological tests.

Objectives To analyse the clinical features, the sexual behaviour and the role of diagnostic tests in a cohort of men with primary syphilis in Milan.

Methods Epidemiological, clinical and laboratory data of male patients with primary syphilis seen at the STI Center of the University of Milan between 2015 and 2019 were retrospectively evaluated. Diagnosis was confirmed by at least one positive diagnostic test of either DFM, TP-NAAT or serology.

Results Among a total of 244 patients, 160 (65.6%) were MSM and 32 (13.1%) were living with HIV. One hundred twenty-four (50.8%) patients had a clinically atypical chancre. Chancres were exclusively extragenital in 30 (12.3%) patients, with MSM being more commonly affected (MSM vs heterosexuals: 16.3% vs 4.8%, respectively; p=0.012), and anal region the most frequently involved site. Chancres were multiple in 68/242 (28.1%) patients and morphologically atypical in 76/244 (31.1%). Diagnosis was obtained by (1) both serology and direct methods in 158/244 patients (64.7%), (2) serology solely in 47/244 (19.3%) and (3) direct methods solely in 39/244 (16%). DFM yielded positive results in 83/139 (59.7%) patients, while TP-NAAT gave positive results in 114/121 (94.2%) patients.

Conclusions Patients with primary syphilis frequently present with morphologically atypical chancres. Furthermore, MSM commonly exhibit extragenital involvement. A combined diagnostic approach including both direct and indirect tests is needed.

  • syphilis
  • serology
  • sexual health
  • clinical STI care
  • dermatology

Data availability statement

All data are available on reasonable request to the corresponding author (

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Data availability statement

All data are available on reasonable request to the corresponding author (

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  • SR and GG are joint first authors.

  • Handling editor Jo Gibbs

  • SR and GG contributed equally.

  • Contributors MC, SR and GG conceived the study and discussed the structure of the manuscript. AVM contributed to the concept of the study and helped with data analysis. SR, GG and MC wrote the manuscript, analysed the patient data and designed the concept of table and figures in close exchange with GC and AVM. GC provided biostatistical support. GL was responsible for laboratory testing. All authors contributed to the discussion and critically revised and edited the manuscript. All authors read and approved the final manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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