The Jarisch-Herxheimer reaction in syphilis: could molecular typing help to understand it better?

J Eur Acad Dermatol Venereol. 2018 Oct;32(10):1791-1795. doi: 10.1111/jdv.15078. Epub 2018 Jun 8.


Objectives: The Jarisch-Herxheimer reaction (JHR) is a febrile inflammatory reaction that may occur in patients after treatment of syphilis. The overall rate is estimated to be 10-25% with broad variations over time. It appears to be related to factors like stage of the disease or reagin titres. In this study, we aimed to describe the incidence of and risk factors including strain typing for JHR among patients with syphilis.

Methods: From January through October 2015, 224 consecutive patients (82 of them with HIV) who were diagnosed with early syphilis were enrolled in this prospective observational study in a referral STI clinic in Barcelona. An appointment was offered to them after 10-14 days of treatment to inquire about the reaction with the use of a standardized form. Treponema pallidum molecular typing was made to detect a possible strain related to reaction.

Results: Overall, 28% of patients developed JHR. This varied from 56% in secondary, 37% in primary to 7% in early latent syphilis. The most frequent types of reaction were fever (57.5%) and worsening of the lesions (31%). The median time to development of JHR was 6 h [IQR 4-10 h] and lasted a median of 9 h [IQR 4-24 h]. The JHR was less probable in early latent compared to primary/secondary syphilis (P = 0.04) and in patients treated with doxycycline compared to those treated with penicillin (P = 0.01). No differences were seen regarding reagin titres or HIV status, and no association with a specific strain was found.

Conclusions: In this study, JHR occurred in a similar frequency as in other contemporary studies. Symptomatic syphilis and treatment with penicillin were associated with an increased risk of JHR, whereas the previous episode of syphilis was associated with a low risk of it. We could not find associations with specific strains of T. pallidum.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Anti-Bacterial Agents / therapeutic use*
  • Arthralgia / epidemiology
  • Chills / epidemiology*
  • Doxycycline / therapeutic use
  • Female
  • Fever / epidemiology*
  • Flushing / epidemiology
  • Headache / epidemiology*
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Molecular Typing
  • Myalgia / epidemiology
  • Penicillins / therapeutic use
  • Prospective Studies
  • Risk Factors
  • Spain / epidemiology
  • Syphilis / drug therapy*
  • Syphilis / microbiology
  • Syphilis, Latent / drug therapy
  • Syphilis, Latent / microbiology
  • Treponema pallidum / classification


  • Anti-Bacterial Agents
  • Penicillins
  • Doxycycline

Supplementary concepts

  • Syphilis, primary
  • Syphilis, secondary